Aging-US

BUFFALO, NY — October 1, 2025 — A new #research paper #featured as the #cover of Volume 17, Issue 9 of Aging-US was published on August 21, 2025, titled “Sex-specific longitudinal reversal of aging in old frail mice.” The study, led by first author Cameron Kato and corresponding author and Aging-US Editorial Board Member Irina M. Conboy from the University of California, Berkeley, reports that a combination of oxytocin and an Alk5 inhibitor (OT+A5i) significantly extended both lifespan and healthspan in frail, elderly, male mice. These rejuvenating effects were not seen in female mice, highlighting key biological differences between the sexes in their response to aging therapies. The researchers tested a dual-drug approach targeting two biological pathways that change with age. Oxytocin, a hormone that declines with aging and supports tissue repair, was combined with an Alk5 inhibitor that blocks the TGF-beta pathway. TGF-beta becomes overactive with age and contributes to chronic inflammation and tissue damage. In this study, frail mice at 25 months of age—roughly equivalent to 75 human years—were treated regularly with the OT+A5i combination. Male mice receiving the therapy lived over 70% longer than untreated controls and showed significant improvements in physical endurance, agility, and memory. According to hazard ratio analysis, the treated males were nearly three times less likely to die at any given time than untreated males. “Treatment of old frail male mice with OT+A5i resulted in a remarkable 73% life extension from that time, and a 14% increase in the overall median lifespan.” The therapy also reduced “biological noise” in circulating blood proteins—an established marker of aging—bringing those levels back to a more youthful state. Short-term benefits, were seen in both sexes, however, after four months of continuous treatment, only the male mice showed sustained improvement in systemic protein balance. Female mice did not experience significant gains in lifespan or healthspan, though middle-aged females did show improved fertility after treatment. These results underscore the importance of understanding sex-specific biology when developing treatments for aging. While the reasons for these differences remain unclear, the findings provide a new model for studying and designing longevity therapies. Oxytocin is already FDA-approved, and Alk5 inhibitors are currently in clinical trials, suggesting that this approach could be translated to humans. With strong results in aged and frail male animals, OT+A5i appears to be a promising candidate for improving late-life health and survival. DOI - https://doi.org/10.18632/aging.206304 Corresponding author - Irina M. Conboy - irina@generationlab.co Abstract video - https://www.youtube.com/watch?v=bpWxDd7hHhM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206304 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, lifespan, healthspan, Alk5 inhibitor, oxytocin, sex-specific differences To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

In this episode of the Longevity & Aging Series, Girish Harinath from AgelessRx joins host Dr. Evgeniy Galimov to discuss a research paper he co-authored in Volume 17, Issue 4 of Aging-US, titled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.” DOI - https://doi.org/10.18632/aging.206235 Corresponding author - Stefanie L. Morgan - stefanie@agelessrx.com Video interview - https://www.youtube.com/watch?v=7-NvskI8Ve0 Longevity & Aging Series - https://www.aging-us.com/longevity Abstract Design: This 48-week decentralized, double-blinded, randomized, placebo-controlled trial (NCT04488601) evaluated the long-term safety of intermittent low-dose rapamycin in a healthy, normative-aging human cohort. Participants received placebo, 5 mg or 10 mg compounded rapamycin weekly. The primary outcome measure was visceral adiposity (by DXA scan), secondary outcomes were blood biomarkers, and lean tissue and bone mineral content (by DXA scan). Established surveys were utilized to evaluate health and well-being. Safety was assessed through adverse events and blood biomarker monitoring. Results: Adverse and serious adverse events were similar across all groups. Visceral adiposity did not change significantly (ηp2 = 0.001, p = 0.942), and changes in blood biomarkers remained within normal ranges. Lean tissue mass (ηp2 = 0.202, p = 0.013) and self-reported pain (ηp2 = 0.168, p = 0.015) improved significantly for women using 10 mg rapamycin. Self-reported emotional well-being (ηp2 = 0.108, p = 0.023) and general health (ηp2 = 0.166, p = 0.004) also improved for those using 5 mg rapamycin. No other significant effects were observed. Conclusions: Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults, and was associated with significant improvements in lean tissue mass and pain in women. Future work will evaluate benefits of a broader range of rapamycin doses on healthspan metrics for longevity, and will aim to more comprehensively establish efficacy. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206235 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, rapamycin, geroscience, longevity, healthspan To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 24, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 7, 2025, titled, “What is the clinical evidence to support off-label rapamycin therapy in healthy adults?” In this study, led by Jacob M. Hands from The George Washington University School of Medicine and Health Sciences, researchers analyzed current research to determine whether low-dose rapamycin can extend healthspan or delay aging in healthy adults. While studies in animals have shown promising results, this review found no clear clinical evidence that the same benefits apply to humans. The findings point to the urgent need for larger, better-designed human trials before recommending rapamycin for off-label use to prevent aging. Rapamycin, originally developed as a drug to suppress the immune system, has gained interest as a possible anti-aging therapy. It works by blocking a key cellular pathway called mTOR, which plays a role in growth and metabolism. In animal studies, blocking this pathway has extended lifespan. However, the translation of these results to humans remains uncertain. The current study examined clinical trials and observational studies involving healthy adults who took low doses of rapamycin or similar drugs. “This paper has reviewed trials of low-dose mTOR inhibition therapy in human subjects.” Some trials showed encouraging signs. For example, older adults treated with low-dose mTOR inhibitors showed stronger immune responses and fewer respiratory infections. Other studies suggested possible improvements in subjective well-being and physical performance, such as walking speed and strength. Still, none of the trials directly showed that rapamycin extends life or clearly slows the aging process. One small study using a biological aging model (PhenoAge) suggested that users might have reduced their biological age by nearly four years, but the estimate was based on average values, not individual patient data. There are also concerns about side effects. While short-term use seems safe, some studies reported increases in blood lipids and markers of inflammation. Research on muscle health produced contradictory findings—some studies suggest rapamycin might reduce the body's ability to build muscle. The impact on mental health is also unclear, with a few participants reporting increased anxiety during treatment. The researchers emphasize that rapamycin's role in human aging is still uncertain. Off-label use is growing among longevity clinics and individuals seeking anti-aging solutions, but there is no standard dose, and long-term safety is unknown. The authors advise that off-label use should be approached with caution, including careful monitoring and full disclosure about the limited evidence. Overall, while animal studies have demonstrated promising effects, human trials have not yet shown that rapamycin can safely or effectively slow aging or extend lifespan. More rigorous and well-controlled studies are necessary before the drug can be considered a reliable option for healthy adults interested in longevity interventions. DOI - https://doi.org/10.18632/aging.206300 Corresponding author - Jacob M. Hands - jacobhands@gwu.edu Abstract video - https://www.youtube.com/watch?v=cdWUenvB_mY Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 23, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 7, 2025, titled “Senescent cell heterogeneity and responses to senolytic treatment are related to cell cycle status during senescence induction.” This study, led by first authors Francesco Neri and Shuyuan Zheng, together with corresponding authors Denis Wirtz, Pei-Hsun Wu, and Birgit Schilling from the Buck Institute for Research on Aging, the USC Leonard Davis School of Gerontology, and Johns Hopkins University, reveals that not all aging cells behave the same. The researchers identified key differences between senescent cell subtypes that may influence how well they respond to senolytic drugs. These findings could help guide the development of more effective therapies for age-related diseases. Senescent cells are aged or damaged cells that stop dividing and accumulate in tissues over time. While they play a role in wound healing and protecting against cancer early in life, they can drive chronic inflammation and tissue decline with age. Researchers are exploring ways to selectively remove these cells using senolytic drugs. However, the large variety of senescent cell types has made it difficult to design treatments that work for all of them. This study aimed to better understand the functional differences among senescent cell subpopulations. Using high-resolution imaging, the team analyzed thousands of human endothelial and fibroblast cells growing in the lab. They observed that cells that exited the cell cycle (stopped dividing) in a later phase showed stronger signs of senescence and were more sensitive to senolytic treatment. These cells also produced more IL-6, a molecule associated with inflammation. The findings suggest that DNA content, which varies depending on the cell cycle phase, plays an important role in how aging cells function and how they respond to drugs. “We found that G2-arrested senescent cells feature higher senescence marker expression than G1-arrested senescent cells.” This is the first clear evidence that senescent cells do not all respond equally to treatment. The results suggest that future senolytic therapies could be more successful if they are designed to target specific subtypes of senescent cells, especially those with greater inflammatory potential. While this research was conducted in laboratory cell cultures, it provides a foundation for studying how these findings apply to living tissues. Future work will examine whether similar patterns occur in the body and how this knowledge could lead to more precise and effective treatments for age-related conditions. Understanding the diversity of aging cells is key to developing therapies that are both safer and more targeted. DOI - https://doi.org/10.18632/aging.206299 Corresponding authors - Denis Wirtz — wirtz@jhu.edu, Pei-Hsun Wu — pwu@jhu.edu, and Birgit Schilling — bschilling@buckinstitute.org Abstract video - https://www.youtube.com/watch?v=x8bhKEFLzqA Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206299 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, imaging, heterogeneity, senolytics, cell cycle To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 18, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 9, 2025, titled “The myokine FGF21 associates with enhanced survival in ALS and mitigates stress-induced cytotoxicity.” In this study, led by first author Abhishek Guha and corresponding author Peter H. King from the University of Alabama at Birmingham and the Birmingham Veterans Affairs Medical Center, researchers discovered that a hormone called FGF21, which is released by muscles, is elevated in people with amyotrophic lateral sclerosis (ALS) and may play a protective role. These findings are especially relevant because ALS is a fatal and currently incurable neurodegenerative disease. Amyotrophic lateral sclerosis is an age-related and progressive condition that affects the nerve cells responsible for muscle control. While some treatments can slow the disease, there is still a need to understand why ALS progresses at different rates in different individuals. “In a prior muscle miRNA sequencing investigation, we identified altered FGF pathways in ALS muscle, leading us to investigate FGF21.” The research team analyzed muscle biopsies, spinal cord tissue, and blood samples from ALS patients and found that FGF21 levels were significantly elevated. This increase was particularly evident in atrophied muscle fibers—those that had shrunk due to nerve loss—and in the surrounding tissue. Importantly, patients with higher plasma levels of FGF21 showed slower loss of function and longer survival, with some living more than six years after diagnosis. Using animal models and cultured cells, the researchers demonstrated that FGF21 levels rise even in the early, symptom-free stages of ALS. The hormone appeared to protect both muscle and motor neurons from stress-related damage. When added to stressed cells, FGF21 improved cell survival and reduced markers of cell death. In human muscle cells, FGF21 also supported the formation of new muscle fibers, a process known as myogenesis. Blood tests revealed that patients with higher levels of FGF21 not only experienced slower disease progression but also tended to have a higher body mass index (BMI), a factor previously associated with longer survival in ALS. This suggests that FGF21 may reflect a patient's ability to counteract ALS through natural protective mechanisms. It could also serve as a biomarker to monitor disease severity and potentially guide treatment decisions. The study also investigated how FGF21 communicates with cells. It found that the hormone's activity depends on a protein called β-Klotho, which was also altered in ALS-affected tissues. These changes were especially noticeable in motor neurons and muscle cells under stress, further highlighting FGF21's role in the body's response to damage. While the study does not show that FGF21 can be used as a treatment, it highlights the hormone as a promising target for future research, clinical trials, and strategies to slow ALS progression by leveraging the body's natural protective systems. DOI - https://doi.org/10.18632/aging.206298 Corresponding author - Peter H. King - phking@uabmc.edu Abstract video - https://www.youtube.com/watch?v=zEGMxQrxZxE Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, fibroblast growth factor, 21 β-Klotho, ALS biomarker, human skeletal muscle, motor neurons To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 16, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 6, 2025, titled “Age-related trends in amyloid positivity in Parkinson's disease without dementia.” In this study, led by first author Keiko Hatano and corresponding author Masashi Kameyama from the Tokyo Metropolitan Institute for Geriatrics and Gerontology in Japan, researchers found that patients with Parkinson's disease (PD) diagnosed in their 80s showed a significantly higher rate of amyloid positivity—an indicator associated with Alzheimer's disease—compared to those diagnosed at a younger age. Importantly, none of the participants had dementia. These findings suggest that older patients with PD may face a greater risk of future cognitive decline and could benefit from early screening for Alzheimer's-related brain changes. Amyloid-beta is considered a key marker of cognitive decline. While it is known that amyloid accumulation contributes to PD with dementia, its role in patients who have not developed cognitive problems remains less understood. This study aimed to explore how age influences amyloid buildup in people with PD who do not yet show signs of dementia. The researchers analyzed data from 89 individuals with PD and no signs of dementia. Participants were divided into two age-based groups: those diagnosed before age 73 (LOW group) and those diagnosed at age 73 or older (HIGH group). Using cerebrospinal fluid samples, they measured levels of amyloid-beta, a standard method for detecting early Alzheimer's-related changes. The findings revealed that 30.6% of the older group tested positive for amyloid, compared to just 10.0% in the younger group. “[…] we elucidated the prevalence of amyloid positivity in patients with PD without dementia, whose mean age at diagnosis was 80.2 years, using CSF Aβ42 levels.” Interestingly, both age groups of Parkinson's patients had a lower rate of amyloid positivity than cognitively normal individuals of the same age in the general population. This unexpected result suggests that PD may alter how amyloid accumulates in the brain, possibly shortening the phase in which amyloid builds up silently before symptoms appear. The authors suggest that amyloid buildup could accelerate the transition from healthy cognition to dementia in patients with PD. The study also observed age-related associations with other biological markers of Alzheimer's disease, such as tau protein levels. As the global population continues to age and the number of older adults diagnosed with PD grows, identifying early warning signs of cognitive decline becomes increasingly important. These findings may help inform future screening approaches and support the development of therapies aimed at delaying or preventing dementia in people with Parkinson's disease. DOI - https://doi.org/10.18632/aging.206297 Corresponding author - Masashi Kameyama - kame-tky@umin.ac.jp Abstract video - https://www.youtube.com/watch?v=AP8S9evzCJw Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206297 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, amyloid positivity, Parkinson's disease without dementia, cerebrospinal fluid Aβ42 To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Idiopathic Pulmonary Fibrosis (IPF) is a progressive lung disease that primarily affects people over the age of 60. It causes scarring in the lung tissue, which gradually reduces lung capacity and makes breathing difficult. Despite years of research, the exact causes of IPF remain largely unknown, and current treatments mainly aim to slow its progression rather than reverse or cure the disease. Because IPF tends to develop later in life, researchers have long suspected a connection with biological aging. This is the focus of a recent study by scientists from Insilico Medicine. Their research, titled “AI-driven toolset for IPF and aging research associates lung fibrosis with accelerated aging,” was published recently in Aging-US, Volume 17, Issue 8. Full blog - https://aging-us.org/2025/09/ai-tools-reveal-how-ipf-and-aging-are-connected/ Paper DOI - https://doi.org/10.18632/aging.206295 Corresponding author - Alex Zhavoronkov - alex@insilico.com Abstract video - https://www.youtube.com/watch?v=24lX2lHbt7o Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206295 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, IPF, generative AI, transformer, proteomics To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 11, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 8, 2025, titled “AI-driven toolset for IPF and aging research associates lung fibrosis with accelerated aging.” In this study, researchers Fedor Galkin, Shan Chen, Alex Aliper, Alex Zhavoronkov, and Feng Ren from Insilico Medicine used artificial intelligence (AI) to investigate the similarities between idiopathic pulmonary fibrosis (IPF), a severe lung disease, and the aging process. Their findings show that IPF is not simply accelerated aging, but a distinct biological condition shaped by age-related dysfunction. This insight may lead to a new approach in how scientists and clinicians treat this complex disease. IPF mainly affects individuals over the age of 60. It causes scarring of lung tissue, making it harder to breathe and often leading to respiratory failure. Current treatments can slow the disease but rarely stop or reverse its progression. The researchers used AI to identify shared biological features between aging and fibrosis, finding new potential targets for therapy. The team developed a “proteomic aging clock” based on protein data from more than 55,000 participants in the UK Biobank. This AI-driven tool accurately measured biological age and found that patients with severe COVID-19, who are at increased risk for lung fibrosis, also showed signs of accelerated aging. This suggests that fibrosis leaves a detectable biological trace, supporting the use of aging clocks in studying age-related diseases. “For aging clock training, we used the UK Biobank collection of 55319 proteomic Olink NPX profiles annotated with age and gender.” They also developed a custom AI model, ipf-P3GPT, to compare gene activity in aging lungs versus those with IPF. Although some genes were active in both, many showed opposite behavior. In fact, more than half of the shared genes had inverse effects. This means IPF does not just speed up aging but also disrupts the body's normal aging pathways. The study identified unique molecular signatures that distinguish IPF from normal aging. While both involve inflammation and tissue remodeling, IPF drives more damaging changes to lung structure and repair systems. This difference could guide the development of drugs that specifically target fibrosis without affecting normal aging. By combining AI with large-scale biological data, the study also introduces a powerful toolset for examining other age-related conditions such as liver and kidney fibrosis. These models may support personalized treatments and expand understanding of the relationships between aging and disease, opening new directions for therapy development. DOI - https://doi.org/10.18632/aging.206295 Corresponding author - Alex Zhavoronkov - alex@insilico.com Abstract video - https://www.youtube.com/watch?v=24lX2lHbt7o Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206295 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, IPF, generative AI, transformer, proteomics To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 9, 2025 — A new #research paper was #published in Volume 17, Issue 8 of Aging-US on August 1, 2025, titled “Causal relationships between gut microbiome and hundreds of age-related traits: evidence of a replicable effect on ApoM protein levels.” In this study, Federica Grosso, Daniela Zanetti, and Serena Sanna from the Institute for Genetic and Biomedical Research (IRGB) of the National Research Council (CNR), Italy, uncovered new associations between gut microbiome and the aging process. The researchers found that certain microbial characteristics may causally influence proteins in the blood linked to inflammation and heart health. These findings could help explain how age-related diseases like cardiovascular conditions and macular degeneration are influenced by changes in the gut ecosystem. The gut microbiome, the collection of microorganisms living in the digestive system, plays a major role in immune function and metabolic health. As people age, this microbial community shifts, often leading to imbalances associated with inflammation and chronic disease. To explore how these changes might affect the body, the researchers used Mendelian Randomization—a method that leverages genetic data—to test over 55,000 possible causal connections between gut microbial characteristics and age-related health indicators. The study identified 91 significant causal relationships. Among them, the researchers found that higher levels of certain gut bacteria were associated with increased risk of age-related macular degeneration. Another finding was the association between a metabolic pathway in the gut, called “purine nucleotides degradation II,” and lower levels of apolipoprotein M (ApoM), a protein that helps protect against heart disease. This result was validated using data from an independent study, strengthening the evidence. “Unlike previous studies, we performed replication analyses for the significant results using independent GWAS datasets, a fundamental step that has often been overlooked.” The study also revealed how some bacteria may affect protein levels differently depending on a person's blood type. Specifically, in individuals with blood type A, certain gut microbes that can break down a sugar called GalNAc may influence proteins related to inflammation and cardiovascular health. This suggests that personalized approaches to managing age-related diseases could consider both gut microbiota and genetic factors like blood type. The research team followed strict guidelines to reduce false findings and confirmed its key results in independent datasets. By carefully testing for reverse causality and other biases, the authors provided strong evidence that the gut microbiome can influence critical aspects of aging biology. Although more research is needed to fully understand the biological pathways involved, these findings suggest that targeting the gut microbiota might help delay or reduce age-related inflammation and disease. The study lays a foundation for future therapeutic strategies that could include diet, probiotics, or other microbiome-based interventions. DOI - https://doi.org/10.18632/aging.206293 Corresponding author - Serena Sanna - serena.sanna@cnr.it Abstract video - https://www.youtube.com/watch?v=CWky6jlHKUs Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

As the global population grows older, understanding what drives the aging process is becoming increasingly important. Diseases like Alzheimer's, cardiovascular conditions, and cancer are more common with age, yet many current treatments only manage symptoms rather than addressing the underlying biological causes. One contributor to aging is the buildup of “senescent” cells—cells that have stopped dividing but do not die. These cells can harm nearby tissues by releasing molecular signals, a process known as secondary senescence. Scientists have found that senescent cells release tiny particles called exosomes. A research team from The Buck Institute for Research on Aging recently discovered that these exosomes carry aging-related messages through the bloodstream. Their study, titled “Exosomes released from senescent cells and circulatory exosomes isolated from human plasma reveal aging-associated proteomic and lipid signatures,” was featured as the cover article in Aging (Aging-US), Volume 17, Issue 8. Full blog - https://aging-us.org/2025/09/how-exosomes-spread-aging-signals-and-could-support-anti-aging-research/ Paper DOI - https://doi.org/10.18632/aging.206292 Corresponding author - Birgit Schilling - bschilling@buckinstitute.org Video short - https://www.youtube.com/watch?v=tcyAZahw-g8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206292 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, proteomics, senescence, exosomes, data-independent acquisitions To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 4, 2025 — A new #research perspective was #published in Volume 17, Issue 8 of Aging (Aging-US) on August 16, 2025, titled “Age-related diseases as a testbed for anti-aging therapeutics: the case of idiopathic pulmonary fibrosis.” In this research perspective, Alex Zhavoronkov, Dominika Wilczok, Feng Ren, and Fedor Galkin, from Insilico Medicine, Buck Institute for Research on Aging, and Duke University, propose a new method to evaluate age-related diseases based on how closely they align with the biological processes of aging. Their analysis shows that idiopathic pulmonary fibrosis (IPF), a progressive lung condition, is one of the diseases most strongly associated with aging. This makes IPF a promising model for testing new anti-aging therapies with the potential to treat multiple age-related conditions. “This perspective explores how aging-related diseases (ARDs) can serve as experimental platforms for discovering new geroprotective interventions.” While many age-related diseases are used as models for aging research, not all accurately reflect the biology of aging. To address this, the authors developed a scoring system that measures how closely a disease is connected to the key hallmarks of aging, such as inflammation, genetic instability, and impaired cellular repair. Using this system, they evaluated 13 common age-related diseases and found that IPF had a particularly high overlap with aging biology. IPF is a chronic disease that causes scarring in the lungs and a rapid decline in lung function. In contrast to the gradual loss of function seen in normal aging, IPF progresses more than five times faster. The authors highlight that IPF shares nearly all of the biological features associated with aging. These similarities make IPF a strong candidate for studying aging and testing therapies that target its underlying causes. The authors also discuss different therapies currently being developed for IPF that are also designed to address aging itself. These include drugs that clear senescent cells, activate telomerase to maintain chromosome health, or repair damaged signaling between cells. Some of these treatments, such as senolytic combinations and AI-discovered compounds like rentosertib, are already showing early promise in preclinical or clinical trials. In addition, the authors point out that IPF's fast progression and clearly measurable outcomes offer an advantage for clinical testing. If a therapy proves effective in IPF, it may also be useful for other conditions that share similar aging-related mechanisms, including diabetes, arthritis, and heart disease. This approach could accelerate drug development and reduce costs by focusing on therapies that target shared biological pathways. Overall, this perspective supports a shift in pharmaceutical research toward treating aging as an underlying cause of many chronic diseases. By positioning IPF as a model for aging-related drug development, the authors propose a strategic pathway for testing and expanding anti-aging therapies across a wide range of health conditions. DOI - https://doi.org/10.18632/aging.206301 Corresponding author - Alex Zhavoronkov – alex@insilico.com Video short - https://www.youtube.com/watch?v=p5ur7itzvSI Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — September 2, 2025 — A new #research paper featured on the #cover of Volume 17, Issue 8 of Aging (Aging-US) was #published on July 30, 2025, titled “Exosomes released from senescent cells and circulatory exosomes isolated from human plasma reveal aging-associated proteomic and lipid signatures.” In this study, led by first authors Sandip Kumar Patel and Joanna Bons, along with corresponding author Birgit Schilling from The Buck Institute for Research on Aging, researchers found that exosomes—tiny particles released by cells—carry molecular signatures that indicate both biological aging and cellular senescence. These signatures include proteins, lipids, and microRNAs associated with inflammation, oxidative stress, and tissue remodeling. The findings could enhance our understanding of biological aging and help in developing future anti-aging therapies. Senescence is a state in which cells stop dividing but remain metabolically active. These cells often release harmful substances, known collectively as the senescence-associated secretory phenotype (SASP), that can affect nearby tissues. This study shows that exosomes are an important component of this secretory profile. The researchers analyzed exosomes from senescent human lung cells and from the blood plasma of both young and older adults. They identified over 1,300 proteins and 247 lipids within these particles. Many of these molecules were significantly altered with age. “In parallel, a small human plasma cohort from young (20–26 years) and old (65–74 years) individuals revealed 1,350 exosome proteins and 171 plasma exosome proteins were altered in old individuals.” Exosomes from older individuals contained more inflammation-related proteins and fewer antioxidants, while those from senescent cells showed lipid changes associated with membrane integrity and cellular stress. These changes suggest that exosomes may play a role in spreading senescence to nearby cells, a process known as secondary senescence. The study also identified distinct patterns in microRNAs—small molecules that regulate gene expression—found in the blood of older adults. Some of these, including miR-27a and miR-874, have previously been associated with cognitive decline and chronic illnesses, highlighting their potential as biomarkers for biological aging. Although the study involved a limited number of samples, it provides strong early evidence that exosomes reflect the molecular changes associated with aging. By showing how these particles carry and possibly spread aging-related signals throughout the body, the research opens new possibilities for diagnosing and treating age-related diseases. DOI - https://doi.org/10.18632/aging.206292 Corresponding author - Birgit Schilling – bschilling@buckinstitute.org Video short - https://www.youtube.com/watch?v=tcyAZahw-g8 Keywords - aging, proteomics, senescence, exosomes, data-independent acquisitions Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 27, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 24, 2025, titled “RNA-binding protein AUF1 suppresses cellular senescence and glycolysis by targeting PDP2 and PGAM1 mRNAs.” In this study, Hyejin Mun, Chang Hoon Shin, Mercy Kim, Jeong Ho Chang, and Je-Hyun Yoon from the University of Oklahoma and Kyungpook National University investigated how changes in cellular metabolism contribute to aging. Their findings offer potential targets for therapies aimed at slowing or reducing the effects of aging. As cells age, they often lose their ability to divide and begin releasing harmful signals that damage nearby tissues. This process, called cellular senescence, is linked to many age-related diseases. A key feature of senescent cells is their altered metabolism, where they use more glucose and oxygen, even when oxygen levels are low. This leads to the production of inflammatory substances and fatty acids, which can accelerate tissue damage. The study examined how these metabolic changes are controlled at the molecular level. Researchers found that AUF1, a protein that binds to RNA, normally helps prevent aging by breaking down two enzymes involved in glucose metabolism: PGAM1 and PDP2. When AUF1 is missing or inactive, these enzymes build up. This causes the cell to produce more energy and inflammatory molecules, which are common features of senescent cells. “Our high throughput profiling of mRNAs and proteins from Human Diploid Fibroblasts (HDFs) revealed that the expression of pyruvate metabolic enzymes is inhibited by the anti-senescent RNA-binding protein (RBP) AUF1 (AU-binding Factor 1).” The team also identified another protein, MST1, which becomes active during cellular stress and aging. MST1 modifies AUF1 in a way that stops it from doing its protective job. As a result, PGAM1 and PDP2 accumulate, leading to faster aging of the cell. Experiments using human fibroblast cells and mouse models confirmed that higher levels of these enzymes are linked to stronger signs of cellular aging. These findings improve our understanding of how metabolism affects the aging process. They highlight the MST1-AUF1-PDP2/PGAM1 pathway as a key factor in the metabolic shift seen in aging cells. Since these enzymes and proteins are already known to be involved in other diseases, existing or future therapies might be used to block this pathway and reduce the effects of aging. This study offers a new direction for senotherapy—a field focused on treating or removing aging cells. By adjusting glucose metabolism through AUF1 and its targets, scientists believe it may be possible to slow aging or limit its effects on tissue function. More research is needed, but these insights could lead to new strategies for managing age-related diseases and promoting healthier aging. DOI - https://doi.org/10.18632/aging.206286 Corresponding authors - Jeong Ho Chang - jhcbio@knu.ac.kr, and Je-Hyun Yoon - jehyun-yoon@ouhsc.edu Video short - https://www.youtube.com/watch?v=Gbu6USUSkgg Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206286 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, AUF1, MST1, senescence, glycolysis To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 26, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 21, 2025, titled “Association of DNA methylation age acceleration with digital clock drawing test performance: the Framingham Heart Study.” In this study, led by first author Zexu Li from the Department of Anatomy and Neurobiology at Boston University Chobanian and Avedisian School of Medicine, and corresponding author Chunyu Liu from Boston University Chobanian and Avedisian School of Medicine and Boston University School of Public Health, researchers found that individuals with signs of faster biological aging had lower scores on a digital cognitive test taken seven years later. The findings suggest that the rate at which a person ages at the molecular level may be associated with how well their brain functions as they grow older. Using data from the Framingham Heart Study, the researchers examined the relationship between biological aging and cognitive health. They used DNA methylation (DNAm) patterns—chemical changes that occur in the DNA with aging, known as epigenetic aging—to estimate biological age acceleration, and used the digital Clock Drawing Test (dCDT) to assess cognitive performance. The dCDT is a computerized version of a traditional pen-and-paper test that evaluates memory, thinking speed, and motor control. It provides an overall score and measures performance in specific areas such as spatial reasoning and movement. Among 1,789 participants, higher levels of epigenetic age acceleration were associated with significantly lower cognitive scores, particularly those over age 65. Of all the epigenetic aging markers examined, the DunedinPACE measure showed the strongest association with reduced brain function in both younger and older adults. Other measures, such as Horvath and PhenoAge, were associated with lower scores only in older adults. Key areas affected included motor skills and spatial reasoning. The researchers also studied blood-based protein markers used in an aging measure called GrimAge. Two proteins, PAI1 and ADM, were closely associated with lower cognitive scores, especially in older individuals. These results suggest that declines in brain and motor functions may reflect broader aging-related changes throughout the body. “Digital cognitive measures displayed stronger associations with most DNAm aging metrics among older compared to younger participants, likely to reflect the cumulative and nonlinear age influences on both brain health and DNAm.” This study supports the idea that epigenetic age may be a more accurate predictor of cognitive decline than chronological age. The dCDT, which is easy to use, automated, and more precise than traditional tools, may help detect early signs of brain aging. When combined with DNAm measures, it could become a valuable part of regular health screenings. Overall, the findings provide strong evidence that faster biological aging is associated with cognitive decline. This research may lead to better ways of identifying and monitoring brain health in aging populations. DOI - https://doi.org/10.18632/aging.206285 Corresponding author - Chunyu Liu - liuc@bu.edu Video short - https://www.youtube.com/watch?v=4hyjDqnPs8w Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 21, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 17, 2025, titled “The influence of cancer on a forensic age estimation tool.” In this study by Charlotte Sutter, Daniel Helbling, Cordula Haas and Jacqueline Neubauer from the Zurich Institute of Forensic Medicine, University of Zurich and Onkozentrum Zurich, the researchers investigated how cancer might affect the accuracy of forensic tools used to estimate a person's age from blood samples. DNA methylation is a natural chemical modification of DNA that changes with age. Forensic scientists can use these changes to predict someone's age from biological traces, such as blood found at a crime scene. However, medical conditions like cancer can alter these patterns and potentially reduce the accuracy of such predictions. This study investigated whether various cancer types influence the DNA markers used in age estimation. “Our study is among the first to show whether it might be necessary to account for the influence of cancer on forensic age estimation tools in order to enhance estimation accuracy as much as possible.” The researchers applied the VISAGE enhanced age estimation tool, a widely used DNA methylation-based method, to blood samples from 100 cancer patients and 102 healthy individuals. Age predictions in the control group were generally accurate, with small average errors. Patients with solid tumors, including breast and lung cancers, showed only slightly less accurate results. In contrast, individuals with blood cancers, particularly chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML), sometimes had large errors, with ages overestimated by as much as 50 years. Despite these few extreme cases, the study found that cancer does not typically have a strong impact on the accuracy of this forensic tool. Most cancer patients, even those undergoing treatment, had DNA methylation patterns similar to those of healthy individuals. The researchers found no consistent differences based on cancer type, stage, or treatment, except in isolated cases involving aggressive forms of cancer. The findings support the continued use of current forensic age estimation methods. While aggressive cancers may occasionally affect prediction accuracy, such cases are rare. The researchers suggest noting these conditions as a possible factor in unusually large errors, without requiring changes to standard practice. This study provides valuable information about how health conditions, such as cancer, may influence DNA-based age estimation. It strengthens confidence in the reliability of forensic age prediction tools, even when applied to individuals with a medical history of cancer. DOI - https://doi.org/10.18632/aging.206281 Corresponding author - Cordula Haas - cordula.haas@irm.uzh.ch Video short - https://www.youtube.com/watch?v=lcpwE50O4ss Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206281 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, forensic age, estimation age prediction, cancer, DNA methylation, age acceleration To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 19, 2025 — A new #research paper was #published in Volume 17, Issue 7 of Aging (Aging-US) on July 7, 2025, titled “Epigenetic age and accelerated aging phenotypes: a tumor biomarker for predicting colorectal cancer.” In this study led by Su Yon Jung from the University of California, Los Angeles, researchers found a strong association between accelerated epigenetic aging and an increased risk of colorectal cancer in postmenopausal women. The study also indicated that lifestyle factors influence this risk. Colorectal cancer is one of the leading causes of cancer-related deaths worldwide, particularly in people over the age of 50. However, individuals do not all age at the same biological rate. Two people of the same chronological age can differ in their biological aging, which reflects the condition of their cells and tissues. This study focused on a specific measure of biological aging known as epigenetic aging, which is based on chemical changes to DNA. The researchers used data from the Women's Health Initiative Database for Genotypes and Phenotypes (WHI-dbGaP), which includes genetic and health information from postmenopausal white women aged 50 to 79. They applied three established “epigenetic clocks” to estimate epigenetic age from blood samples collected up to 17 years before a colorectal cancer diagnosis. These clocks measure how quickly a person is aging at the molecular level by tracking DNA methylation. Women with a higher epigenetic age than expected were significantly more likely to develop colorectal cancer “[…]we examined biological aging status in PBLs via three well-established epigenetic clocks—Horvath's, Hannum's and Levine's […].” The study also explored the role of lifestyle in modifying this risk. Women who consumed more fruits and vegetables showed no increased risk, even if they were epigenetically older. In contrast, women with both lower fruit and vegetable intake and signs of accelerated aging were up to 20 times more likely to develop colorectal cancer. This suggests that a healthy diet may help reduce cancer risk associated with biological aging. Another key finding involved women who had both ovaries removed before natural menopause. These women had a higher epigenetic age and, when combined with accelerated aging, a greater likelihood of developing colorectal cancer. This highlights the potential influence of hormonal and reproductive factors on aging and disease risk. The researchers validated their findings across several independent datasets, supporting the potential of blood-based epigenetic aging markers as early indicators of colorectal cancer risk. These markers could help guide early detection and prevention strategies in aging populations. However, the authors emphasize the need for independent large-scale replication studies. Overall, this study contributes to a better understanding of the association between epigenetic aging and cancer. It also supports the idea that modifiable lifestyle factors may reduce disease risk, even among those aging more rapidly at the cellular level. DOI - https://doi.org/10.18632/aging.206276 Corresponding author - Su Yon Jung - sjung@sonnet.ucla.edu Video short - https://www.youtube.com/watch?v=cq1MphQKmSk Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

A new #study published as the #cover of Aging (Aging-US) Volume 17, Issue 7, explores how factors in young human blood may affect the biological age of human skin. Researchers from Beiersdorf AG, Research and Development Hamburg in Germany, used a microphysiological co-culture system—a lab-based model simulating human circulation—to test the effects of young versus old blood serum on skin cells. The findings suggest that bone marrow-derived cells play a key role in converting blood-borne signals into effects that support skin rejuvenation. Understanding Skin Aging and Systemic Influence As we age, the skin's ability to regenerate declines, while its biological age increases. This contributes to visible signs of aging and a weakened barrier function. While cosmetic treatments can improve appearance, they rarely target the cellular processes underlying skin aging. Animal studies have shown that exposure to young blood can promote tissue repair and rejuvenation, likely due to molecules circulating in the bloodstream. However, reproducing these effects in human skin has proven difficult. Applying young serum directly to skin tissue has not produced significant results, indicating that additional cellular interactions may be required. Full blog - https://aging-us.org/2025/08/skin-rejuvenation-how-young-blood-and-bone-marrow-influence-it/ Paper DOI - https://doi.org/10.18632/aging.206288 Corresponding author - Elke Grönniger - elke.groenniger@beiersdorf.com Video short - https://www.youtube.com/watch?v=_4spcgzPcEk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206288 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, skin rejuvenation, microphysiological systems, systemic factors, bone marrow model, human serum To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 14, 2025 — A new #research paper was #published in Volume 17, Issue 7, of Aging (Aging-US) on July 3, 2025, titled “Frailty associates with respiratory exacerbations and mortality in the COPDGene cohort.” In this study, led by first author Eleanor Kate Phillips from Brigham and Women's Hospital and corresponding author Dawn L. DeMeo from Brigham and Women's Hospital and Harvard Medical School, researchers investigated how frailty impacts lung health and survival in individuals with a history of cigarette smoking. They found that frailty raises the risk of lung attacks and death, even in smokers with preserved lung function. This result shows why all current and former smokers should be checked for frailty. Frailty is a condition that makes the body more vulnerable to illness, especially in older adults. This study focused on more than 2,600 adults with a history of heavy smoking, many of whom showed no signs of lung damage on standard tests. At the second follow-up visit, participants were categorized as robust, prefrail, or frail and followed for about three years. Researchers tracked how often they experienced respiratory attacks, such as episodes of severe coughing or breathlessness, and whether they survived during that period. “COPDGene is a cohort study of individuals aged 45–80 with a minimum 10 pack-year smoking history.” The results showed that people who were frail had a three- to five-fold higher chance of developing serious or frequent respiratory attacks compared to those who were robust. These risks were not limited to people with chronic lung disease. In fact, many frail participants with normal lung function still faced a significantly higher chance of lung attacks and death. Even those in the “prefrail” stage, a milder form of frailty, were more likely to experience health complications. The research team also found that frailty was associated with an accelerated pace of biological aging, measured using a DNA-based test called DunedinPACE. This supports the idea that frailty may reflect deeper biological changes in the body that go beyond what traditional lung function tests can detect. These findings challenge the idea that standard lung tests can rule out future respiratory complications in people with a history of smoking. Altogether, the study shows that simple frailty checks could help identify early health problems, allowing for timely interventions that may prevent hospitalizations and potentially save lives. The study suggests that frailty screening may be a valuable tool in public health efforts to reduce respiratory disease and improve outcomes for aging adults. DOI - https://doi.org/10.18632/aging.206275 Corresponding author - Dawn L. DeMeo - redld@channing.harvard.edu Video short - https://www.youtube.com/watch?v=G1XQhQN6PQ8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206275 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, frailty, cigarette smoking, respiratory exacerbations, COPD, epigenetic aging To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 12, 2025 — A new #research perspective was #published in Aging (Aging-US) on July 8, 2025, titled “Exercise as a geroprotector: focusing on epigenetic aging.” In this perspective, led by Takuji Kawamura from Tohoku University, researchers reviewed existing evidence from scientific studies showing that regular exercise, physical activity, and fitness may influence epigenetic aging and potentially reverse it, offering a promising way to extend healthspan and improve long-term health. Epigenetic aging refers to changes in the body's DNA that reflect how quickly a person is aging at the molecular level. It is measured using epigenetic clocks, which analyze patterns of DNA methylation, a chemical modification that can affect gene activity. Unlike chronological age, which simply counts the number of years lived, epigenetic aging presents a more accurate picture of how well the body's cells and tissues are functioning. This process is influenced by various factors, including lifestyle, and has become a powerful tool for studying aging. This perspective highlights that while general physical activity, such as walking or doing household tasks, offers health benefits, structured exercise routines that are planned, repetitive, and goal-directed appear to have stronger effects on slowing epigenetic aging. Physical fitness, especially high cardiorespiratory capacity, is also closely associated with slower epigenetic aging. The authors also discuss key findings from both human and animal studies. In mice, structured endurance and resistance training reduced age-related molecular changes in muscle tissue. In humans, multi-week exercise interventions demonstrated reductions in biological age markers in blood and skeletal muscle. One study found that sedentary middle-aged women reduced their epigenetic age by two years after just eight weeks of combined aerobic and strength training. Another study showed that older men with higher oxygen uptake levels, a key measure of cardiovascular fitness, had significantly slower epigenetic aging. “These findings suggest that maintaining physical fitness delays epigenetic aging in multiple organs and supports the notion that exercise as a geroprotector confers benefits to various organs.” The research also examines which organs benefit most from exercise. While skeletal muscle has been a central focus, new evidence shows that regular physical training may also slow aging in the heart, liver, fat tissue, and even the gut. In addition, Olympic athletes were found to have slower epigenetic aging than non-athletes, suggesting that long-term, intensive physical activity may have lasting anti-aging effects. The authors call for further research to understand why some individuals respond more strongly to exercise than others and how different types of training influence aging in various organs. They also point out the importance of developing personalized exercise programs to maximize anti-aging benefits. Overall, the findings support the growing recognition that maintaining physical fitness is not only essential for daily health but may also serve as one of the most effective tools for slowing the body's internal aging process. DOI - https://doi.org/10.18632/aging.206278 Corresponding author - Takuji Kawamura - takuji.kawamura.b8@tohoku.ac.jp Video short - https://www.youtube.com/watch?v=Wro3_wBovdE To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 11, 2025 — Aging (Aging-US) is proud to support a milestone event for the global senescence and aging research community. This coming September 16-19, 2025, Rome, Italy will host two back-to-back events that will define the next chapter of senescence science and translation: -10th Annual International Cell Senescence Association (ICSA) Conference -Senotherapeutics Summit – organized with the Phaedon Institute This combined program could not come at a more important time. The field is entering a transformative phase: -Multiple clinical trials on senolytics and senomorphics are now reporting results, offering the first real-world evidence of their therapeutic potential. -Exciting new discoveries in senescence mechanisms, biomarkers, and tissue-specific roles are reshaping our understanding of when and how to target these cells. For the first time, the leading fundamental science meeting on cellular senescence will be directly connected with a global summit dedicated to the clinical and commercial development of senotherapeutics. This unique integration will allow participants to seamlessly move from bench to bedside discussions, exploring both the latest research and its translation into therapies that could transform how we approach aging and age-related diseases. Highlights include: -Keynotes from pioneers driving both discovery science and translational innovation -Sessions on mechanisms, biomarkers, and emerging targets -Industry and regulatory panels on clinical trial design, safety, and approval pathways -Case studies from ongoing and completed human trials -Networking with leaders from academia, biotech and pharma Celebrate a decade of ICSA and help chart the path for the next generation of senescence science and therapeutics. Registration is still open: https://icsa2025rome.com/ To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — August 1, 2025 — A new #research paper featured on the #cover of Volume 17, Issue 7 of Aging (Aging-US) was #published on July 25, 2025, titled “Systemic factors in young human serum influence in vitro responses of human skin and bone marrow-derived blood cells in a microphysiological co-culture system.” The study, led by first author Johanna Ritter and corresponding author Elke Grönniger from Beiersdorf AG, Research and Development Hamburg, shows that components in young human blood serum can help restore youthful properties to skin, but only when bone marrow cells are also present. This discovery highlights the role of bone marrow in supporting skin health and may allow for novel approaches aimed at slowing or reversing visible signs of aging. The research explored how factors present in blood serum, already known to influence aging in animal studies, act on human cells. Using an advanced system that mimics human circulation, the researchers connected a 3D skin model with a 3D bone marrow model. They found that young human serum alone was not enough to rejuvenate skin. However, when bone marrow cells were present, these serum factors changed the activity of those cells, which then secreted proteins that rejuvenated skin tissue. “Interestingly, we detected a significant increase in Ki67 positive cells in the dynamic skin model co-cultured with BM model and young serum compared to the model co-cultured with BM and old serum, indicating an improved regenerative capacity of the tissue.” Detailed analysis indicated that young serum stimulated the bone marrow to produce a group of 55 proteins, with 7 of them demonstrating the ability to boost cell renewal, collagen production, and other features associated with youthful skin. These proteins included factors that improved energy production in cells and reduced signs of cellular aging. Without the interaction between skin and bone marrow cells, these rejuvenating effects did not occur. This finding explains why earlier experiments in mice, where young and old animals shared a blood supply, showed rejuvenation across organs. It suggests that bone marrow-derived cells are critical messengers that transform signals from blood into effects on other tissues, including the skin. While these results are preclinical and not from human trials, they offer a starting point for new strategies in regenerative medicine and skin care. By identifying specific proteins that may carry rejuvenating signals, the study points to a new way to address age-related changes. Researchers emphasize that further studies will be needed to confirm these effects in humans and to test how these proteins can be safely and effectively applied in future therapies. Overall, this research is an important step in understanding how young blood serum factors influence human tissue and could guide the development of novel methods to maintain healthier skin as people age. DOI - https://doi.org/10.18632/aging.206288 Corresponding author - Elke Grönniger - elke.groenniger@beiersdorf.com Video short - https://www.youtube.com/watch?v=_4spcgzPcEk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206288 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 30, 2025 — A new #research paper was #published in Aging (Aging-US) on July 23, 2025, titled “Second generation DNA methylation age predicts cognitive change in midlife: the moderating role of childhood socioeconomic status.” In this study, led by Sophie A. Bell and Eric Turkheimer from the University of Virginia, researchers investigated how biological aging, measured through DNA methylation, is connected to changes in thinking skills during midlife and whether childhood socioeconomic status influences this relationship. Biological age provides a picture of how the body is aging that goes beyond simply counting years. In this study, researchers used both first- and second-generation DNA methylation clocks—tools that track chemical changes in DNA as markers of aging. GrimAge and PhenoAge, the second-generation clocks designed to reflect broader health and aging processes, were more accurate at predicting long-term changes in Intelligence Quotient (IQ) than the first-generation models that only estimated chronological age. The study analyzed 287 participants from the Louisville Twin Study, which is a long-term project that has followed twins from childhood into midlife. “DNAmAge was estimated with five commonly used algorithms, or epigenetic clocks (Horvath, Horvath Skin and Blood, GrimAge, and PhenoAge).” The results showed that twins with more rapid epigenetic aging had a larger drop in IQ scores. This pattern remained even after considering genetic background and early family environment, made possible by the twin-based design. Importantly, the relationship was strongest in twins who had grown up in families with lower socioeconomic status. This finding suggests that early-life disadvantage may make individuals more vulnerable to the effects of biological aging on brain health. This research adds knowledge to earlier work showing that childhood poverty can influence long-term health. It also highlights the value of second-generation epigenetic clocks as early indicators of brain aging. Unlike the first generation of clocks, these newer tools capture broader biological changes such as inflammation, disease risk, and behaviors like smoking. Although smoking partly explained the results because it strongly influences DNA methylation, it did not fully account for the association between accelerated biological aging and cognitive decline. This suggests that both life experiences and lifestyle factors shape body and brain aging. By combining decades of developmental data with a genetically informed twin design, the study provides new evidence that biological aging, especially when shaped by childhood adversity, is a key factor in midlife cognitive decline. These findings may inform early health strategies that consider both social and biological risks and support the use of second-generation methylation clocks to predict age-related cognitive changes. DOI - https://doi.org/10.18632/aging.206284 Corresponding authors - Sophie A. Bell - bvf7pa@virginia.edu, and Eric Turkheimer - ent3c@virginia.edu Video short - https://www.youtube.com/watch?v=vopDdS1olXw Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206284 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 28, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 13, 2025, titled “Development of a novel transcriptomic measure of aging: Transcriptomic Mortality-risk Age (TraMA).” In this study, led by Eric T. Klopack from the University of Southern California, researchers created a new RNA-based aging measure that predicts health risks and mortality. This measure, called Transcriptomic Mortality-risk Age (TraMA), uses gene expression data to estimate a person's biological aging. This finding offers a new and potentially more accurate way to track aging and understand health risks, especially for older adults. Aging is a complex biological process that affects multiple systems in the body and increases the risk of disease and death. Scientists have long looked for reliable ways to measure biological aging. While DNA methylation and blood biomarkers are commonly used, this study focused on RNA—a molecule that reflects gene activity. By analyzing RNA sequencing data from nearly 4,000 U.S. adults aged 50 and older, the team developed TraMA to predict the probability of dying within four years. TraMA proved to be a strong and independent predictor of early death, multiple chronic diseases, poor cognitive function, and difficulties with daily activities. It was also tested in another large group of long-lived families and in several smaller datasets from patients with conditions like diabetes, sepsis, and cancer. The results confirmed the tool's usefulness across different populations and health conditions. “TraMA was also externally validated in the Long Life Family Study and several publicly available datasets.” Unlike earlier RNA-based aging measures, which were often built using small or non-representative samples, TraMA was developed using modern RNA sequencing technology results and a nationally representative dataset. This increases its reliability and potential for broad public health applications. The tool also demonstrated unique advantages over popular biological aging measures like GrimAge and PhenoAge, capturing distinct aspects of aging and health decline. Importantly, TraMA tracks biological processes related to inflammation, immune function, and kidney and brain health, systems that play key roles in aging. It was also sensitive to behavioral and socioeconomic factors. For instance, smoking, obesity, and low physical activity were associated with older TraMA scores. TraMA was also sensitive to changes in biological aging. In one study, researchers measured TraMA at two different time points and found that the more recent scores were better at predicting who would die. This suggests that TraMA can track changes in a person's aging as their health evolves. It also performed well in both large-scale surveys and small clinical samples, making it a useful tool in many types of research. By offering a new, accurate, and flexible method for measuring biological aging, TraMA may help researchers better understand how genes, lifestyle, and environment influence aging. This tool opens the door to more precise research on improving health and extending lifespan. DOI - https://doi.org/10.18632/aging.206272 Corresponding author - Eric T. Klopack - klopack@usc.edu Video short - https://www.youtube.com/watch?v=Tl0CApUz8cU Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 23, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 16, 2025, titled “rDNA copy number variation and methylation from birth to sexual maturity.” In this study, led by first authors Alina Michler and Sarah Kießling along with corresponding author Thomas Haaf from Julius Maximilians University in Germany, researchers explored how ribosomal DNA (rDNA) copy number and methylation change from infancy to adolescence. They discovered that the epigenetic changes often associated with aging in adults do not occur before sexual maturity. This finding offers new insights into when the biological aging process truly begins. Ribosomal DNA plays a critical role in producing proteins essential for cell survival. The researchers analyzed blood samples from 280 individuals, ranging from newborns to 18 years of age, including healthy individuals and those with developmental delays. They measured the number of rDNA copies and examined how genes are switched on or off through methylation, a chemical modification of DNA. The results showed that while adults experience a gradual loss of active rDNA copies and increased methylation—a hallmark of aging—these changes were absent in children and teenagers. In fact, during childhood and adolescence, the number of active, unmethylated rDNA copies slightly increased. These findings support the long-debated idea that biological aging begins only after the body reaches reproductive maturity. Until that point, cells appear to actively maintain rDNA in a youthful state, ensuring that protein production remains efficient. This may help explain why children and teenagers are better at resisting many age-related diseases and why their cells recover more easily from stress. The study also shows that changes in rDNA copy numbers are not associated with unexplained developmental delays. This suggests these epigenetic processes are probably not involved in early-life syndromes. The findings highlight how the body works to preserve genetic stability during childhood and raise important questions about what triggers the shift to aging-related changes after puberty. “Collectively our data suggest that the rDNA hypomethylation state is actively maintained in somatic tissues of young individuals.” The insights gained from this research expand the understanding of the molecular clock of aging. They suggest potential new ways to delay aging processes by exploring how youthful rDNA methylation patterns are maintained. As scientists continue to investigate these mechanisms, the study provides a clear foundation for future research aimed at extending cellular health beyond adolescence. DOI - https://doi.org/10.18632/aging.206271 Corresponding author - Thomas Haaf - thomas.haaf@uni-wuerzburg.de Video short - https://www.youtube.com/watch?v=Ww21u33uUhk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206271 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, absolute rDNA copy number, active rDNA copy number, deep bisulfite sequencing, developmental delay, droplet digital PCR To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

A new #study published recently in Volume 17, Issue 6, examines a novel treatment for women with ovarian failure. Researchers from IVI Clinics Alicante in Spain investigated a procedure called Stem Cell Regenera, which uses the body's own stem cells and platelet-rich plasma to activate dormant follicles in the ovaries. This innovative protocol could expand options for patients with ovarian failure who have not responded to conventional fertility therapies. Understanding Ovarian Failure Ovarian failure affects women's ability to conceive by reducing the quantity and quality of eggs in the ovaries. Conditions like Poor Ovarian Response, Diminished Ovarian Reserve, and Premature Ovarian Insufficiency are key reasons for infertility and make it hard to use assisted reproduction methods like in vitro fertilization (IVF). Standard fertility treatments often fail to improve outcomes for these patients, leaving donor eggs as the primary alternative. However, recent advances in regenerative medicine have raised the possibility of restoring ovarian function using cellular therapies. Emerging research suggests that the right biological conditions could reactivate dormant follicles within the ovaries, potentially helping patients to use their eggs. Full blog - https://aging-us.org/2025/07/stem-cell-regenera-a-regenerative-approach-to-activating-dormant-ovarian-follicles/ Paper DOI - https://doi.org/10.18632/aging.206274 Corresponding author -Amparo Santamaria - Amparo.santamaria@ivirma.com Author interview - https://www.youtube.com/watch?v=oRFJNwnXZWI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206274 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 21, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 27, 2025, titled “Enhancing oocyte activation in women with ovarian failure: clinical outcomes of the Stem Cell Regenera study using G-CSF mobilization of peripheral blood stem cells and intraovarian injection of stem cell factor-enriched platelet rich plasma in real-world-practice.” This study, led by Amparo Santamaria with co-authors Ana Ballester and Manuel Muñoz from IVI Clinics Alicante, evaluates the effectiveness and safety of a regenerative treatment that may enable women with ovarian failure to regain the ability to produce viable eggs. The approach combines stem cell mobilization and enriched plasma injections into the ovaries to stimulate follicle growth. It provides an alternative for patients experiencing infertility due to poor ovarian response, diminished ovarian reserve, or premature ovarian insufficiency. Researchers evaluated the Stem Cell Regenera treatment in 145 women, aged 26 to 44 years, who had not responded to conventional fertility therapies. The procedure involved mobilizing the body's own stem cells using granulocyte colony-stimulating factor (G-CSF), followed by an injection of platelet-rich plasma enriched with stem cell factors directly into the ovaries. This method was designed to activate dormant follicles and promote ovarian regeneration. Nearly 70% of participants demonstrated oocyte activation, defined as increased follicle growth or a rise in key hormone levels. Approximately 7% achieved spontaneous pregnancies, and 14% conceived through in vitro fertilization (IVF) after treatment. These results indicate that the therapy stimulates ovarian activity and may increase the chances of conception in selected patients. “The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates.” No severe adverse effects were reported. Most participants tolerated the treatment well, with only mild and transient symptoms such as headaches or fatigue. The use of the patient's own cells minimized the risk of immune reactions and helped ensure the treatment was safe. The findings provide evidence of effectiveness and safety for the Stem Cell Regenera protocol in a clinical setting. While the study was retrospective observational, the outcomes support further investigation through larger controlled trials to confirm long-term benefits and identify which patient populations may gain the greatest benefit from this approach. This research contributes to the growing field of regenerative medicine in reproductive health, offering clinicians additional tools to address infertility in women with complex ovarian conditions. DOI - https://doi.org/10.18632/aging.206274 Corresponding author -Amparo Santamaria - Amparo.santamaria@ivirma.com Author interview - https://www.youtube.com/watch?v=oRFJNwnXZWI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206274 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 17, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 9, 2025, titled “Developing a quantitative estimate of muscle age acceleration by a novel phenotypic clock: cross-sectional study in healthy, middle-aged and older adults.” In this study, led by first authors Lucia Ventura, Antonella Cano and Marco Morrone, along with corresponding author Franca Deriu from the University of Sassari, researchers introduce a new method to predict how muscles age, offering an early warning system for sarcopenia, the condition of age-related muscle loss. The study demonstrates how a simple, low-cost approach can identify middle-aged and older adults at higher risk for declining muscle health, allowing timely preventive strategies. The researchers developed a tool called Muscle Age Acceleration (MAA), which measures how quickly an individual's muscles are aging compared to their actual age. By analyzing physical performance tests and body composition in 215 healthy participants aged 50 to 90 years, the researchers found that about 25% of individuals experience accelerated muscle aging. These individuals had a higher probability of developing sarcopenia, despite appearing healthy and not yet having received a diagnosis of the condition. Sarcopenia reduces muscle strength and physical performance, being a growing concern for older adults. It contributes to frailty, falls, and an increased risk of disability. Despite greater awareness, this condition often goes undetected until significant muscle loss occurs. This new muscular clock offers an opportunity to detect subtle changes in muscle health before they progress to more severe stages. By using common tests such as handgrip strength, walking speed, and mobility assessments, the MAA tool can classify individuals as having accelerated, normal, or decelerated muscle aging. Those with accelerated muscle aging also showed small changes in blood markers, suggesting early and hidden inflammation linked to muscle decline. This finding indicates that MAA may act as both a predictor of muscle-related aging and an indicator of overall health risks. “According to MAA, three trajectories were identified: accelerated agers displayed higher risk for sarcopenia (19%), as compared to normal (9%; p < 0.0001) and decelerated (2%; p < 0.0001), paralleled by significant subclinical alterations of haemato-chemical markers in accelerated agers.” If validated in future studies, this innovative approach could transform how clinicians and caregivers screen for early signs of sarcopenia. Its simplicity makes it suitable for use in clinics and community settings, helping older adults maintain independence and quality of life as they age. In summary, these findings highlight the importance of monitoring muscle health and physical performance in older adults. By detecting early signs of muscle aging with tools like MAA, interventions such as exercise and dietary changes can be introduced earlier, potentially delaying or preventing sarcopenia and its complications. DOI - https://doi.org/10.18632/aging.206269 Corresponding author - Franca Deriu - deriuf@uniss.it Video short - https://www.youtube.com/watch?v=kc9i0aJNNp0 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Dr. Amparo Santamaria describes a #research paper she co-authored that was #published in Volume 17, Issue 6 of Aging (Aging-US), titled “Enhancing oocyte activation in women with ovarian failure: clinical outcomes of the Stem Cell Regenera study using G-CSF mobilization of peripheral blood stem cells and intraovarian injection of stem cell factor-enriched platelet rich plasma in real-world-practice.” DOI - https://doi.org/10.18632/aging.206274 Corresponding author -Amparo Santamaria - Amparo.santamaria@ivirma.com Video interview - https://www.youtube.com/watch?v=oRFJNwnXZWI Abstract The study assesses the effectiveness and safety of the Stem Cell Regenera Treatment for oocyte activation in women with ovarian failure, including conditions such as Poor Ovarian Response (POR), Diminished Ovarian Reserve (DOR), and Premature Ovarian Insufficiency (POI). This retrospective observational study was conducted from January 2023 to December 2024 at the IVIRMA Alicante Clinics in Spain. Women diagnosed with ovarian failure participated in the study, which involved mobilizing Hematopoietic Stem Cells from bone marrow into peripheral blood using granulocyte colony- stimulating factor (G-CSF). This was followed by an intraovarian injection of Stem Cell Factor- enriched Platelet Rich Plasma (SCFE-PRP). The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates. Oocyte activation was defined as an increase in total Antral Follicle Count of three or more follicles after treatment and/or at least a 20% rise in Anti-Müllerian Hormone levels. Safety was assessed based on adverse effects. Pregnancy rates were evaluated for both spontaneous gestation and following in vitro fertilization (IVF) treatment. A total of 145 women participated: the overall activation rate was 68.28%, with 7.07% achieving spontaneous gestation and 14.14% achieving pregnancy following IVF. Mobilization of CD34+ cells was successful in all participants, with an average collection of 32.96 CD34+ cells/μl. No severe adverse effects were observed. The study concluded that the Stem Cell Regenera Treatment is effective and safe for oocyte activation in women with ovarian failure in real-world practice. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206274 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 15, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 5, 2025, titled “Senescence caused by telomerase inactivation in myeloid, mesenchymal, and endothelial cells has distinct effects on cancer progression.” In this study, first author Joseph Rupert, along with corresponding author Mikhail G. Kolonin and colleagues from The Brown Foundation Institute of Molecular Medicine for the Prevention of Human Diseases, McGovern Medical School, at The University of Texas Health Sciences Center at Houston, investigated how aging-related changes in different cell types affect cancer progression. By turning off telomerase in specific cell populations in mice, the researchers discovered that cell aging, or senescence, can slow primary tumor growth but also trigger unexpected effects. This work sheds light on the complex relationship between aging cells and cancer and may help guide future anti-cancer strategies. The team used genetically modified mice to deactivate telomerase, the enzyme that maintains chromosome ends, specifically in immune, connective tissue, and blood vessel cells. This caused these cells to enter a state of senescence, where they stop dividing and release inflammatory signals. The researchers then implanted breast, prostate, and pancreatic cancer cells into the mice and tracked how tumors developed. They found that when telomerase was inactivated in immune cells or connective tissue cells, tumors grew more slowly. However, these tumors showed signs of increased tissue damage and potential aggressiveness. Interestingly, when telomerase was turned off in endothelial cells, which cover blood vessels, tumors shrank and became poorly supplied with blood, leading to oxygen deprivation. In the case of pancreatic cancer cells, this low-oxygen environment made them more likely to spread to the liver, highlighting a potential risk of targeting these cells. “[…] this study shows that senescence and metabolic dysfunction resulting from telomerase inactivation in distinct cells in the tumor microenvironment have different effects on tumor growth and metastasizing of carcinomas.” This research provides important insights into how aging cells within the tumor microenvironment (TME) influence cancer behavior. While senescence in certain cell types can help suppress tumor growth, it may also create conditions that favor cancer metastasis. These findings highlight the need to consider cell type-specific effects when developing therapies that target senescent cells. By mapping how different cell populations contribute to cancer progression in aging tissues, this study opens the door for more precise approaches to prevent both tumor growth and spread. DOI - https://doi.org/10.18632/aging.206268 Corresponding author - Mikhail G. Kolonin - mikhail.g.kolonin@uth.tmc.edu Video short - https://www.youtube.com/watch?v=py8wFKj7enE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206268 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, telomerase, myeloid, mesenchymal, endothelial To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 10, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on June 7, 2025, titled “Spermidine supplementation and protein restriction protect from organismal and brain aging independently.” In this study, led by YongTian Liang and Stephan J. Sigrist from Freie Universität Berlin, Charité Universitätmediz Berlin, and the Leibniz-German Center for Neurodegenerative Diseases (DZNE), researchers investigated how spermidine, a natural substance in the body, and protein intake levels influence aging in fruit flies. They found that spermidine supplementation and changes in protein intake influenced brain health and aging in distinct ways. These insights could guide the development of new strategies to slow age-related decline in humans. “In this study, we combined low- and high-protein diets (2% versus 12% yeast in food) with spermidine supplementation in aging Drosophila fruit flies.” Aging of the brain and body contributes to cognitive decline and diseases in older populations. Scientists have long explored dietary restriction and fasting as ways to slow these processes. This study reveals that spermidine supplementation supports brain health by enhancing mitochondrial function and memory, while protein restriction independently promotes longevity and protects against movement decline. The researchers discovered that spermidine improved memory and preserved physical activity in aging flies regardless of protein intake. In contrast, reducing protein alone boosted mitochondrial activity and extended lifespan without directly enhancing memory. Importantly, the combined approach of protein restriction and spermidine supplementation provided additive benefits, suggesting potential for synergistic effects. This work highlights that spermidine acts through a pathway involving hypusination, a vital process where cells modify proteins to support energy production and repair, while protein restriction works via nutrient-sensing pathways that promote longevity. These independent mechanisms may explain why combining the two interventions offers greater protection against aging effects. Although conducted in flies, the study underscores the possibility of designing dietary and supplement-based interventions to combat human age-related decline. As spermidine levels naturally decline with age, supplementation combined with moderated protein intake could offer a safe way to promote brain health and longevity in humans. The authors point out that it takes further studies in mammals and humans to validate these results. If confirmed, such strategies could lead the way for accessible approaches to promote healthy aging and reduce the burden of cognitive disorders in older populations. DOI - https://doi.org/10.18632/aging.206267 Corresponding authors - YongTian Liang - yongtian.tim.liang@gmail.com, and Stephan J. Sigrist - stephan.sigrist@fu-berlin.de Video short - https://www.youtube.com/watch?v=QfxpK9tka7U Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206267 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, brain aging, spermidine, protein restriction, mitochondria To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 8, 2025 — As populations worldwide continue to age, understanding the mechanisms and manifestations of cognitive aging is increasingly urgent for science, medicine, and society. Age-related cognitive decline ranges from mild memory lapses to the onset of dementia, and is shaped by a complex interplay of molecular, cellular, systemic, and social determinants. In this special collection, Aging (Aging-US) seeks to bring together cutting-edge research that spans the cellular and molecular underpinnings of cognitive aging with insights into the psychosocial, behavioral, and environmental factors that modulate its course. By integrating basic biology with translational and societal dimensions, this collection aims to foster a holistic understanding of how and why cognitive function changes with age—and what can be done to preserve it. We welcome original research articles, reviews, and perspectives across model systems and human studies, particularly those that promote interdisciplinary insights and translational potential. POTENTIAL TOPICS Molecular and Cellular Mechanisms -Senescence, inflammation, and neurodegeneration in cognitive decline -Mitochondrial dysfunction and oxidative stress in aging neurons -Neurovascular aging and blood-brain barrier integrity -Single-cell and spatial transcriptomics of the aging brain -mTOR, autophagy, and proteostasis in age-related cognitive impairment -The role of glial cells (microglia, astrocytes) in brain aging Genetics and Biomarkers -Genetic risk factors and epigenetic modifications associated with cognitive aging -Biomarkers of cognitive resilience and vulnerability -Neuroimaging and fluid-based biomarkers in aging populations Interventions and Lifestyle Factors -Cognitive benefits of caloric restriction, exercise, or senolytic therapies -Preclinical and clinical trials targeting aging pathways to prevent cognitive decline -Impact of sleep, nutrition, and metabolic health on cognition in older adults -Use of cognitive strategies and compensatory techniques to maintain or enhance function in aging Environmental and Social Contexts -Impact of social isolation, education, and socioeconomic status on cognitive trajectories -Lifelong cognitive reserve and its determinants -Cross-cultural and demographic studies on aging and cognition -Digital health tools for monitoring or enhancing cognitive function in the elderly SUBMISSION DETAILS: -Submission Deadline: March 31, 2026 -Manuscript Format: Please follow the journal's submission guidelines -Peer Review: All submissions will undergo a rigorous peer-review process -Submission Link: https://aging.msubmit.net/cgi-bin/main.plex To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 8, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 6, on May 30, 2025, titled “Impact of waist-to-hip and waist-to-height ratios on physical performance: insights from the Longevity Check-up 8+ project.” In this study, researchers led by first author Anna Maria Martone and corresponding author Elena Levati from the Fondazione Policlinico Universitario “Agostino Gemelli” IRCCS and Università Cattolica del Sacro Cuore found that adults with higher waist-to-hip and waist-to-height ratios tend to have poorer physical performance. These simple body shape measures emerged as important tools for assessing strength and mobility, which are essential for maintaining independence as people age. The analysis included data from more than 10,000 Italian adults aged 18 to 98 years who participated in the Longevity Check-up 8+ project, a nationwide health initiative aimed at promoting healthy lifestyles and raising awareness of cardiovascular risks. Researchers measured participants' waist-to-hip (WHR) and waist-to-height (WHtR) ratios and assessed their physical function using the five-repetition chair stand test, a standard evaluation of lower body strength and mobility. “Among 10690 participants (mean age 57.0 ± 14.8 y; 54% females), men exhibited higher WHR and WHtR and a higher prevalence of abnormal values (61% and 71%).” The results showed that individuals with higher waist-to-hip and waist-to-height ratios took longer to complete the test, reflecting reduced physical function. Even after adjusting for lifestyle factors such as diet, exercise habits, and cardiovascular health, these ratios remained strongly linked to poorer performance. The waist-to-height ratio, in particular, proved to be a more effective predictor of physical ability across different age and gender groups. These findings highlight how abdominal fat, already tied to serious health risks like heart disease and diabetes, may also impair mobility and independence as people age. Monitoring waist measurements could help identify individuals at risk of functional decline, offering a simple tool to support public health in aging populations. The waist-to-height ratio is especially valuable because of its simplicity and practicality. Requiring only waist and height measurements, it can be easily used in clinical settings and community health programs to screen for potential mobility issues. Encouraging healthy waist sizes through balanced diets and regular exercise could help preserve physical performance and delay age-related decline. These findings may guide future prevention strategies. By identifying individuals at higher risk, healthcare professionals can implement targeted interventions to support long-term health and independence. DOI - https://doi.org/10.18632/aging.206260 Corresponding author - Elena Levati - elena.levati01@icatt.it Video short - https://www.youtube.com/watch?v=WqGlZ1qGZPI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206260 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, physical performance, body composition, waist-to-hip ratio, waist-to-height ratio, chair-stand test To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

A new study published recently as the cover of Aging Volume 17, Issue 6, describes a new method to estimate how fast the brain is aging. By analyzing lipids, or fat molecules, in brain tissue, researchers from the National University of Singapore and Hanze University of Applied Sciences created a biological “clock” called DoliClock. This innovation highlights how conditions such as autism, schizophrenia, and Down syndrome are associated with accelerated brain aging. Understanding Brain Aging As people grow older, their brains naturally change. However, in many neurological disorders, these changes seem to appear earlier and progress more rapidly. Disorders like autism, schizophrenia, and Down syndrome reduce quality of life and contribute to premature death. Scientists have long searched for better ways to measure biological age in the brain to understand these processes and develop strategies to slow them down. Most existing methods for estimating biological age rely on genetic markers, such as DNA methylation, which are chemical modifications of DNA. While useful, these approaches may not fully capture the complexity of aging, especially in the brain. Lipids, which are essential components of brain cells and play important roles in energy storage and signaling, offer another perspective. Full blog - https://aging-us.org/2025/07/doliclock-a-lipid-based-clock-for-measuring-brain-aging/ Paper DOI - https://doi.org/10.18632/aging.206266 Corresponding author - Brian K. Kennedy - bkennedy@nus.edu.sg Video short - https://www.youtube.com/watch?v=-FEiyj9PjBE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206266 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, aging clock, down syndrome, autism, schizophrenia, dolichol To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Dr. Andres Cardenas, from the Department of Epidemiology and Population Health at Stanford University, joins host Dr. Evgeniy Galimov to discuss a research paper he co-authored in Volume 17, Issue 2 of Aging (Aging-US), titled “Exposome-wide association study of environmental chemical exposures and epigenetic aging in the National Health and Nutrition Examination Survey.” DOI - https://doi.org/10.18632/aging.206201 Corresponding author - Andres Cardenas - andresca@stanford.edu Video interview - https://www.youtube.com/watch?v=A1I6qoVwkfM Longevity & Aging Series - https://www.aging-us.com/longevity Abstract Epigenetic clocks can serve as pivotal biomarkers linking environmental exposures with biological aging. However, research on the influence of environmental exposures on epigenetic aging has largely been limited to a small number of chemicals and specific populations. We harnessed data from the National Health and Nutrition Examination Survey 1999-2000 and 2001-2002 cycles to examine exposome-wide associations between environmental exposures and epigenetic aging. A total of 8 epigenetic aging biomarkers were obtained from whole blood in 2,346 participants ranging from 50-84 years of age. A total of 64 environmental exposures including phthalates, metals, pesticides, dioxins, and polychlorinated biphenyls (PCBs) were measured in blood and urine. Associations between log2-transformed/standardized exposure measures and epigenetic age acceleration (EAA) were assessed using survey-weighted generalized linear regression. A 1 standard deviation (SD) increase in log2 serum cadmium levels was associated with higher GrimAge acceleration (beta = 1.23 years, p = 3.63e-06), higher GrimAge2 acceleration (beta = 1.27 years, p = 1.62e-05), and higher DunedinPoAm (beta = 0.02, p = 2.34e-05). A 1 SD increase in log2 serum cotinine levels was associated with higher GrimAge2 acceleration (beta = 1.40 years, p = 6.53e-04) and higher DunedinPoAm (beta = 0.03, p = 6.31e-04). Associations between cadmium and EAA across several clocks persisted in sensitivity models adjusted for serum cotinine levels, and other associations involving lead, dioxins, and PCBs were identified. Several environmental exposures are associated with epigenetic aging in a nationally representative US adult population, with particularly strong associations related to cadmium and cotinine across several epigenetic clocks. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206201 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenetic aging, environmental exposures, exposome, epigenetics Please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 2, 2025 — A new #research perspective was #published in Aging (Aging-US) Volume 17, Issue 6, on May 29, 2025, titled “Peto's paradox's relevance is off the scale.” In this perspective, Dr. Mirre J.P. Simons from the University of Sheffield argues that Peto's paradox—a well-known concept in cancer biology—remains a vital framework for understanding cancer resistance in large animals. Dr. Simons challenges recent claims that dismiss the paradox and emphasizes that the unexpectedly low cancer rates in large species still require explanation. This insight is especially relevant for aging and cancer research. Peto's paradox highlights a puzzling observation: larger animals like elephants and whales, despite having far more cells than smaller animals, do not have proportionally higher cancer rates. If each cell had an equal chance of turning cancerous, bigger animals should develop cancer much more frequently. But in reality, they do not. This suggests that evolution has equipped these animals with powerful biological defenses against cancer. “The field of comparative biology into ageing and cancer was given a strong impetus when Peto identified that humans have substantially more cells than mice, but do not have substantially larger incidence of cancer.” Dr. Simons explains that recent studies showing small increases in cancer with body size do not disprove the paradox. The expected increase, based on basic mathematical models, would be massive—many times greater than what is observed. Instead of rejecting Peto's paradox, the field should focus on understanding how large animals suppress cancer so effectively. The author points out that the key to resolving this paradox may lie in traits that evolved alongside body size, such as tissue environments or specialized cell-control mechanisms. These features might reduce the probability of cancer developing, even in animals with millions or billions more cells than humans. Importantly, this perspective underscores the clinical potential of studying species that resist cancer naturally. Studying these natural defenses may help researchers uncover new ways to understand, prevent, or manage cancer. Because cancer risk increases with age in most species, understanding how some animals limit both aging and cancer may also help explain how these two processes are connected. Dr. Simons cautions against oversimplifying cancer biology by focusing only on genetic mutations. Instead, understanding how cells interact with their environment, known as the tissue microenvironment, may offer deeper insight into how cancer develops or is prevented. By reaffirming the importance of Peto's paradox, this research perspective encourages the scientific community to explore the evolutionary tools nature uses to fight cancer. These insights could improve our understanding of cancer and inspire new strategies to support healthier aging. DOI - https://doi.org/10.18632/aging.206258 Corresponding author - Mirre J.P. Simons - m.simons@sheffield.ac.uk Video short - https://www.youtube.com/watch?v=sDaq07zX2TM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206258 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cancer, evolution To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — July 1, 2025 — A new #research paper, featured on the #cover of Aging (Aging-US) Volume 17, Issue 6, was #published on June 4, 2025, titled “DoliClock: a lipid-based aging clock reveals accelerated aging in neurological disorders.” This study, led by first author Djakim Latumalea from the National University of Singapore and Hanze University of Applied Sciences, with corresponding author Brian K. Kennedy from the National University of Singapore, introduces DoliClock, a biological aging clock based on lipid profiles in the human brain. The researchers found that individuals with autism, schizophrenia, and Down syndrome show signs of accelerated brain aging compared to individuals without these conditions. The discovery offers a new approach to measuring brain aging using lipid markers instead of traditional DNA-based methods. The team developed DoliClock using lipidomic data from post-mortem prefrontal cortex samples. Lipids are fat-like molecules that play a key role in brain health. Changes in lipid patterns can reflect the biological age of brain tissue. The study focused on a specific class of lipids called dolichols, which increase gradually with age. The DoliClock model was trained to predict biological age by analyzing levels of dolichols and other lipid molecules. It accurately estimated brain age and revealed higher aging rates in individuals with neurological disorders. One notable finding was a sharp increase in lipid profile variability—also known as entropy—around the age of 40. This suggests a disruption in lipid metabolism during midlife, possibly caused by changes in the mevalonate pathway, a critical biological process involved in producing lipids like cholesterol and dolichol. These disruptions may contribute to aging-related brain decline. The study also found that dolichol levels could serve as reliable biomarkers of aging. Their consistent increase with age and strong influence on DoliClock's predictions make them especially useful. In individuals with autism, schizophrenia, and Down syndrome, the clock indicated more advanced biological brain aging than expected, supporting the idea that these conditions are associated with premature aging. DoliClock offers a new perspective in aging research, complementing existing biological clocks based on DNA or protein markers. Because it relies on lipids, it may detect aspects of aging that other tools cannot. While the current model is based on brain tissue samples, future research may examine whether similar lipid patterns can be identified in more accessible fluids such as blood or cerebrospinal fluid. “These findings suggest that lipidomics can provide valuable insights into the molecular mechanisms of brain aging and neurological disorders.” This study highlights the growing potential of lipidomics in the study of aging and neurological disorders. It opens the door to new biomarkers that could help researchers and clinicians better monitor brain aging and develop more targeted interventions for age-related and neurodevelopmental diseases. DOI - https://doi.org/10.18632/aging.206266 Corresponding author - Brian K. Kennedy - bkennedy@nus.edu.sg Video short - https://www.youtube.com/watch?v=-FEiyj9PjBE Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Recent discoveries in #aging research reveal a powerful insight: the biological changes that lead to chronic #diseases begin far earlier than most people realize—often in midlife, well before symptoms appear. This early phase offers a valuable opportunity for prevention. As highlighted in a recent editorial by Marco Demaria, Editor-in-Chief of Aging and a researcher at the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen, and the University of Groningen (RUG), the aging process itself – not just the diseases it produces – can and should be a primary focus of healthcare. The Problem with Traditional Medicine While modern healthcare has extended lifespan and improved treatment for many diseases, it tends to be insufficient in addressing the complex needs of aging populations. Older individuals frequently experience multiple chronic conditions simultaneously, such as cardiovascular disease, diabetes, cancer, and neurodegenerative disorders. This state of multimorbidity complicates care, increases the use of multiple medications, and reduces quality of life. The dominant traditional healthcare system, which typically begins only after symptoms appear, is costly and insufficient for addressing the interconnected nature of these conditions. A New Model for Healthcare: Insights from the Editorial In his recent editorial, “Rethinking healthcare through aging biology,” published in Aging Volume 17, Issue 5, Dr. Demaria outlines a shift from disease-specific treatment to targeting the biological mechanisms of aging itself, a more integrated and forward-looking approach. He presents three evolving healthcare models. Full blog - https://aging-us.org/2025/06/a-new-vision-for-healthcare-addressing-aging-before-disease-begins/ Paper DOI - https://doi.org/10.18632/aging.206262 Corresponding author - Marco Demaria - m.demaria@umcg.nl Video short - https://www.youtube.com/watch?v=xR-16cjHnQY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206262 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, healthcare, senolytics, epigenetics, medical education To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 25, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 5, on May 28, 2025, titled “Investigating telomere length in progeroid syndromes: implications for aging disorders.” In this study, led by first author Luma Srour and corresponding authors Yosra Bejaoui and Nady El Hajj, from Hamad Bin Khalifa University, Qatar Foundation, researchers investigated whether shortened telomeres, a marker of cellular aging, are present across various rare genetic disorders that mimic early aging, known as progeroid syndromes. The study found that telomere shortening, also called telomere attrition, is not a shared characteristic of all these disorders. This finding is important because it challenges the belief that telomere loss is a common thread in premature aging and could help refine how these syndromes are studied and treated. Progeroid syndromes are rare conditions that cause individuals to display symptoms of aging far earlier than expected. While some of these syndromes share signs of typical aging, others arise from very different genetic alterations. Researchers focused on comparing telomere length in individuals with several of these syndromes to better understand how aging develops at the cellular level. Telomeres are protective ends of chromosomes that shorten as cells divide, acting as a biological clock linked to aging and disease. Using DNA methylation data from blood samples, the team analyzed telomere length in patients with six progeroid syndromes: Werner Syndrome, Hutchinson-Gilford Progeria Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, Dyskeratosis Congenita, Cerebroretinal Microangiopathy with Calcifications and Cysts, and Wiedemann-Rautenstrauch Syndrome. They found significant telomere shortening only in classical Werner Syndrome, Berardinelli-Seip Congenital Lipodystrophy type 2, and Dyskeratosis Congenita. Other syndromes, including the widely studied Hutchinson-Gilford Progeria Syndrome, did not show this pattern. “To investigate whether progeroid syndromes have telomere attrition, we calculated telomere length using the DNAmAge web-based calculator.” The findings suggest that telomere shortening cannot be used as a universal marker for all forms of premature aging. In fact, some syndromes linked to DNA repair problems showed telomere damage, while others with different genetic mutations did not. These results indicate that the underlying biology of each syndrome is crucial in determining whether telomere shortening plays a role. Researchers also compared telomere lengths in people with genetic variants known to protect against age-related diseases. Those with protective genes had longer telomeres than people with progeroid syndromes. This study challenges assumptions about aging in rare disorders and highlights the need for more personalized approaches in aging research. By identifying which syndromes involve telomere attrition, it opens new avenues for treating or delaying aging-related symptoms. Future research may explore other biological factors behind premature aging and how genetic differences influence the aging process. DOI - https://doi.org/10.18632/aging.206255 Corresponding authors - Yosra Bejaoui - yob4003@qatar-med.cornell.edu, and Nady El Hajj - nelhajj@hbku.edu.qa Video short - https://www.youtube.com/watch?v=T8vjIuYHaFg To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 24, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 5, on May 20, 2025, titled “Short-term moderate caloric restriction in the rhesus macaque attenuates markers of ovarian aging in select populations.” In this study, led by first author Emma S. Gargus and corresponding author Francesca E. Duncan from Feinberg School of Medicine at Northwestern University, researchers explored how dietary changes impact ovarian aging in female rhesus macaques. They found that a three-year moderate reduction in caloric intake preserved a youthful distribution of ovarian follicles and reduced age-related tissue stiffness. These findings are relevant to women's health as they suggest that caloric restriction (CR) may help delay the decline in reproductive function associated with aging. Ovarian aging, which leads to reduced fertility and hormone production, is one of the earliest signs of aging in women. This study investigated whether a 30% reduction in caloric intake could protect the ovaries from age-related damage in nonhuman primates (NHP), whose reproductive biology closely mirrors that of humans. Ovaries were collected from young (10–13 years) and old (19–26 years) rhesus macaques who were either on a diet of moderate caloric restriction or a control diet for three years. “To test the effect of CR on follicle number, follicles were analyzed in histological sections from animals across experimental cohorts: Young Control, Young CR, Old Control, Old CR (n = 4–8/group).” Although total follicle numbers still declined with age, caloric restriction helped maintain the types of follicles most associated with reproductive potential. In older monkeys who were still cycling, even if irregularly, caloric restriction preserved more primordial follicles, the key indicators of ovarian reserve, than in those on a normal diet. The benefits of caloric restriction were also seen in the structure of ovarian tissue. Normally, aging leads to fibrosis, a stiffening of the ovarian environment caused by increased collagen and decreased hyaluronic acid. This study showed that caloric restriction reduced this fibrotic process, suggesting a more supportive environment for maintaining reproductive health. While the diet did not stop the overall loss of follicles with age, it improved the proportion of younger, more viable follicles in aging ovaries. The timing of the dietary intervention also appeared to matter. Positive effects were more noticeable in older animals with irregular cycles than in those who had completely stopped cycling. This indicates that starting caloric restriction at a certain point in the reproductive lifespan may yield the best results. This research is an important step to identifying lifestyle-based strategies that can extend reproductive longevity. Although further studies are needed to test these findings in humans, the work supports the potential of moderate dietary changes to delay ovarian aging and help preserve fertility later in life. DOI - https://doi.org/10.18632/aging.206253 Corresponding author - Francesca E. Duncan - f-duncan@northwestern.edu Video short - https://www.youtube.com/watch?v=AvgZR3X3nyU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206253 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Dr. Josh Mitteldorf summarizes his #research perspective #published in Volume 17, Issue 5 of Aging (Aging-US), titled “Methylation clocks for evaluation of anti-aging interventions.” DOI - https://doi.org/10.18632/aging.206245 Corresponding author - Josh Mitteldorf - aging.advice@gmail.com Author interview - https://www.youtube.com/watch?v=efgNvr5ezTk Video short - https://www.youtube.com/watch?v=YjUvpqMzCGc Abstract Methylation clocks have found their way into the community of aging research as a way to test anti-aging interventions without having to wait for mortality statistics. But methylation is a primary means of epigenetic control, and presumably has evolved under strong selection. Hence, if methylation patterns change consistently at late ages it must mean one of two things. Either (1) the body is evolved to destroy itself (with inflammation, autoimmunity, etc.), and the observed methylation changes are a means to this end; or (2) the body detects accumulated damage, and is ramping up repair mechanisms in a campaign to rescue itself. My thesis herein is that both Type 1 and Type 2 changes are occurring, but that only Type 1 changes are useful in constructing methylation clocks to evaluate anti-aging interventions. This is because a therapy that sets back Type 1 changes to an earlier age state has stopped the body from destroying itself; but a therapy that sets back Type 2 changes has stopped the body from repairing itself. Thus, a major challenge before the community of epigenetic clock developers is to distinguish Type 2 from Type 1. The existence of Type 1 epigenetic changes is in conflict with conventional Darwinian thinking, and this has prompted some researchers to explore the possibility that Type 1 changes might be a form of stochastic epigenetic drift. I argue herein that what seems like directed epigenetic change really is directed epigenetic change. Of five recent articles on “stochastic methylation clocks,” only one (from the Conboy lab) is based on truly stochastic changes. Using the Conboy methodology and a methylation database, I construct a measure of true methylation drift, and show that its correlation with age is too low to be useful. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206245 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, methylation, stochastic, entropy, programmed aging, aging clock, epigenetic clock To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 18, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 5, on May 12, 2025, titled “Frailty transitions in electronic health records: who first? what first?” The study, led by Fabienne Hershkowitz Sikron from Meuhedet HMO, analyzed how frailty develops over time in older adults using electronic health record data from nearly 120,000 individuals aged 65 and above. Researchers found that frailty worsened in over 13% of participants within a year, particularly among women, adults aged 85 or older, and people with chronic illnesses, while nearly 3% showed signs of improvement. The findings highlight early indicators of decline that could help guide preventive care and improve outcomes for aging populations. Frailty is a condition marked by increased vulnerability to health complications and tends to change gradually. The study used the Meuhedet Electronic Frailty Index (MEFI) to track yearly transitions in frailty among older adults in Israel. While many people remained in the same frailty category, a significant proportion experienced deterioration in just one year, and a smaller group improved. “Worsening frailty is defined as a higher frailty level one year later in 2024 compared to 2023. A new frailty deficit is defined as a deficit appearing in 2024 that was not present in 2023.” Those most at risk of worsening included adults over 85, women, individuals from lower socio-economic backgrounds, and members of the Arab sector. Additional predictors of decline included recent hospitalizations, multiple chronic diseases, and signs of cognitive or mobility issues. Importantly, the first signs of worsening were often not new chronic conditions but more manageable health deficits such as sleep disturbances, muscle weakness, hearing loss, and memory decline. Those who improved were more likely to be younger, male, from higher socio-economic backgrounds, and have fewer chronic conditions and hospitalizations. The study also found that common chronic illnesses like diabetes and hypertension were often already present and did not usually signal the beginning of frailty progression. Instead, declines in overall function and quality of life were more frequently the first new issues to appear. This suggests that early intervention on modifiable health deficits could delay or prevent further decline. This work is one of the first large-scale, real-world studies to identify both who is most likely to worsen first and what health problems typically appear first. The authors emphasize the importance of using routinely collected electronic medical data to monitor frailty and tailor care. By doing so, health providers can implement timely strategies to reduce disease burden and support aging individuals in maintaining independence. These findings support the creation of proactive health programs focused on maintaining physical strength, cognitive function, and sensory abilities. Preventing frailty progression can reduce hospitalizations, ease disease burden, and help older adults maintain independence and a higher quality of life. DOI - https://doi.org/10.18632/aging.206247 Corresponding author - Fabienne Hershkowitz Sikron - fabian_hershkowitz@meuhedet.co.il Video short - https://www.youtube.com/watch?v=4xa11ApI4ho Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 17, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 5, on May 1, 2025, titled “Oxytocin modulates insulin and GLP-1 secretion in pancreatic islets.” In this study, scientists from Fukushima Medical University School of Medicine investigated how the hormone oxytocin (Oxt) influences insulin levels by acting on specific cells in the pancreas. The team led by first author Kasumi Hattori and corresponding authors Kenju Shimomura and Yuko Maejima discovered that oxytocin may indirectly increase insulin secretion by triggering another hormone, GLP-1, from within the pancreas. This finding could lead to new strategies for improving blood sugar control in people with diabetes. Oxytocin is commonly known for its roles in childbirth and social bonding, but scientists have also been exploring its effects on metabolism. While previous studies offered mixed results about whether oxytocin raises or lowers blood sugar, this research brings new clarity. The study focused on oxytocin's impact on insulin and a hormone called GLP-1, which helps regulate insulin production. Researchers tested this by using mice with and without oxytocin receptors and found that oxytocin's ability to raise insulin levels depended on the presence of these receptors and high blood sugar conditions. Researchers found that oxytocin stimulates the release of “intra-islet GLP-1,” a form of GLP-1 produced inside the pancreas rather than the intestine. In the pancreas, insulin is produced by beta cells, while alpha cells produce glucagon, a hormone that raises blood sugar. But recent research, including this study, has shown that alpha cells can also release GLP-1, which in turn helps beta cells secrete insulin. Oxytocin appears to increase this internal GLP-1 release, especially when blood sugar levels are high, thereby leading to insulin release in a natural and targeted way. In this study researchers were also able to detect the difference between oxytocin's effect on blood sugar and its effect on insulin. They observed that right after oxytocin was given, blood sugar levels rose in all mice—even in those that lacked oxytocin receptors. However, only the mice with working oxytocin receptors showed a later increase in insulin. This suggests that oxytocin may trigger insulin production through a separate, receptor-dependent pathway involving the hormone GLP-1. "WT mice showed a significant increase in insulin levels at 15-min, while OxtR KO mice did not." This indirect action—oxytocin triggering alpha cells to release GLP-1, which then acts on beta cells—may represent a novel mechanism for controlling insulin release. It also explains why oxytocin does not increase insulin in low-glucose conditions, making it a potentially safer option for regulating blood sugar. As treatments for type 2 diabetes increasingly focus on GLP-1–based drugs, this study opens the door to using oxytocin or similar compounds to naturally enhance the body's own insulin-producing system. With further research, this mechanism could help develop new therapies that better mimic the body's natural glucose control, particularly beneficial for older adults with diabetes. DOI - https://doi.org/10.18632/aging.206244 Corresponding authors - Kenju Shimomura - shimomur@fmu.ac.jp, and Yuko Maejima - maejimay@fmu.ac.jp Video short - https://www.youtube.com/watch?v=C0K6uDX4z8U To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 12, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 5, on May 3, 2025, titled “APOE genotype and biological age impact inter-omic associations related to bioenergetics.” In this study, led by first author Dylan Ellis and corresponding author Noa Rappaport from the Institute for Systems Biology, researchers discovered that different versions of the APOE gene—particularly ε2 and ε4—are linked to metabolic patterns associated with aging and Alzheimer's disease risk. Both variants were linked to increased levels of diacylglycerols, a type of fat molecule connected to insulin resistance and inflammation, suggesting shared disruptions in how the body regulates energy. The research team analyzed data from over 2,200 adults without an Alzheimer's diagnosis, exploring how APOE genotypes influence biological age, a measure of health that reflects how quickly or slowly someone is aging at a cellular level. They found that the same metabolic disturbances seen in ε2 carriers were also present in people considered biologically older, revealing unexpected overlap between genetic risk and aging-related metabolic changes. To examine these connections in more detail, the researchers used a multi-omics approach, combining blood-based metabolism and protein data, gut bacteria analysis from stool samples, and clinical chemistry data. This method allowed them to map how genetic differences and biological aging affect the body's energy systems. They observed altered connections between glucose metabolism, inflammatory markers, and key molecules that play roles in energy production, indicating early disruptions that could contribute to age-related diseases. One of the study's surprising findings was that the ε2 variant, usually associated with longer life and reduced Alzheimer's risk, showed metabolic traits similar to those found in insulin-resistant individuals. This suggests that ε2 may carry metabolic disadvantages earlier in life, with its protective effects becoming more pronounced later. Conversely, ε4—linked to greater Alzheimer's risk—may exert its influence based on interactions with lifestyle factors like diet, sex, and overall health status. “‘Omics association patterns of ε2-carriers and increased biological age were also counter-intuitively similar, displaying significantly increased associations between insulin resistance markers and energy-generating pathway metabolites.” By identifying these shared biological signatures, this study offers a new framework for understanding how genes and metabolism work together to influence aging. These findings could support more personalized health strategies aimed at delaying biological aging and reducing the risk of chronic diseases. As aging populations grow worldwide, understanding these pathways is essential to improving healthspan. DOI - https://doi.org/10.18632/aging.206243 Corresponding author - Noa Rappaport - noa.rappaport@isbscience.org Video short - https://www.youtube.com/watch?v=75hZQoO5U0U Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206243 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, apolipoprotein E (APOE), biological age, metabolism, Alzheimer's disease (AD), insulin resistance To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

As we age, our brains become more sensitive to stress and disease. A recent study sheds light on a lesser-known risk: reduced oxygen levels. The study, titled “Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age” and recently published as the cover for Volume 17, Issue 5 of Aging (Aging-US), found that low oxygen—also called hypoxia—can harm the aging brain by disrupting the blood-brain barrier (BBB). This damage may contribute to cognitive decline, memory problems, and an increased risk of dementia. Understanding Hypoxia in the Brain The brain relies on a steady supply of oxygen to stay healthy. When oxygen levels fall—a condition known as hypoxia—the brain undergoes changes to adapt. These changes include the remodeling of blood vessels and, importantly, a weakening of the blood-brain barrier. The BBB acts as a filter, protecting brain tissue from harmful substances. When it breaks down, it can lead to inflammation, brain cell damage, and cognitive issues. Hypoxia is common in older adults, especially those with conditions like sleep apnea, chronic obstructive pulmonary disease (COPD), heart failure, and asthma. That is why understanding the connection between low oxygen and the aging brain is crucial for preventing long-term neurological damage. Full blog - https://aging-us.org/2025/06/oxygen-deprivation-and-the-aging-brain-a-hidden-trigger-for-cognitive-decline/ Paper DOI - https://doi.org/10.18632/aging.206241 Corresponding author - Richard Milner - rmilner@sdbri.org Video short - https://www.youtube.com/watch?v=Nr6rTm7aJRo Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206241 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, blood-brain barrier integrity, endothelial, proliferation, microglia, chronic mild hypoxia, hypoxic threshold To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 10, 2025 — The Ride for Roswell, one of the USA's largest cycling events supporting cancer research, returns to Buffalo on Saturday, June 28, 2025. Hosted annually by Roswell Park Comprehensive Cancer Center, this community-wide event brings together riders, volunteers, and supporters to raise funds for cancer research, celebrate survivors, and honor those lost to the disease. Among the returning participants is the Open Access Team, led by team captain Sergei Kurenov. This year, the team is once again proudly sponsored by Impact Journals, the publisher of open access journals Aging, Oncotarget, Genes & Cancer, and Oncoscience. “For the last 10 years, I have continuously participated in the Ride for Roswell in honor of those who have bravely fought cancer,” said Kurenov. “This journey is deeply personal for me. My father battled cancer, and some of my closest friends have fought through prostate and lung cancer with incredible strength.” This year, the Open Access Team rides in honor of Dr. Mikhail (Misha) Blagosklonny, a visionary scientist who dedicated his career to advancing cancer and aging research. As the founding Editor-in-Chief of Aging, Oncotarget and Oncoscience, Dr. Blagosklonny was a pioneer of open-access publishing. His groundbreaking work on mTOR signaling and rapamycin transformed our understanding of cancer biology and healthy lifespan extension. The 2025 Ride for Roswell features nine route options, ranging from 4 to 100 miles, all beginning at the University at Buffalo North Campus. Riders from across the USA and beyond are invited to participate and make a meaningful impact in the fight against cancer. This ride is more than just a journey on two wheels—it's a commitment to building a future where no one has to fear a cancer diagnosis. There is still time to support the Open Access Team in the 2025 Ride for Roswell. Whether by donating, joining the team, or sharing their story, every action brings us closer to better treatments, deeper understanding, and, ultimately, a cure. Visit the Open Access Team page - https://give.roswellpark.org/site/TR/SpecialEvents/General?team_id=23320&pg=team&fr_id=2020 To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 10, 2025 — A new #research perspective was #published in Aging (Aging-US) Volume 17, Issue 5, on May 5, 2025, titled “Methylation clocks for evaluation of anti-aging interventions.” In this perspective article, Dr. Josh Mitteldorf explores how current epigenetic clocks—used to estimate biological age—might mislead scientists trying to evaluate anti-aging therapies. The paper challenges a widespread assumption: that all changes in DNA methylation with age are equally valid for measuring biological decline. Dr. Mitteldorf proposes that failing to distinguish between different types of epigenetic changes could lead to inaccurate conclusions, potentially even favoring treatments that reduce repair processes rather than extend healthy lifespan. Methylation clocks have become a popular tool in aging research. These clocks use patterns of DNA methylation, a form of gene regulation that changes over time, to predict a person's biological age. Because human aging trials are long and expensive, these clocks offer a faster way to evaluate whether a therapy slows or reverses aging. However, this article warns that not all methylation changes are equal in meaning or effect. The perspective identifies two main categories of methylation changes that occur with age. One type, called 'Type 1,' seems to support the idea that aging may be programmed, with gene activity changing in ways that could cause damage, such as more inflammation or increased cell loss. The second type, “Type 2,” involves increased gene activity aimed at repairing age-related damage. If a therapy reduces the activity of Type 2 genes, it may appear to slow aging while actually interfering with the body's repair response. “Paradoxically, an intervention that “sets back” the body's methylation clock to a younger state is shutting off vital repair mechanisms, so it is likely inimical to health and longevity.” This distinction is important because most methylation clocks, including popular models like GrimAge, do not separate these two types. As a result, they may incorrectly suggest that a treatment is reversing aging when it is only suppressing beneficial repair mechanisms. According to Dr. Mitteldorf, this could lead researchers to draw the wrong conclusions and unintentionally slow down progress in anti-aging research. The author also addresses a growing trend in the scientific community that aims to explain age-related methylation as random drift rather than directed change. In a pilot analysis using publicly available data, Dr. Mitteldorf attempted to construct a clock based purely on stochastic, or random, changes. The results showed a weak correlation with age, suggesting that random drift is an unreliable basis for assessing biological aging. Dr. Mitteldorf argues that most age-related methylation changes are likely intentional and regulated, rather than random. If so, epigenetic clocks must be refined to reflect the biological purpose behind methylation shifts. Without distinguishing between changes that indicate damage and those that indicate repair, current clocks may not only mismeasure age but also misguide intervention strategies. This article highlights the urgent need to improve how methylation data are interpreted before such clocks can reliably assess anti-aging therapies. A clearer understanding of these molecular patterns could help reshape the future of aging research and therapy evaluation. DOI - https://doi.org/10.18632/aging.206245 Corresponding author - Josh Mitteldorf - aging.advice@gmail.com To learn more about the journal, please visit our website at https://www.Aging-US.com. MEDIA@IMPACTJOURNALS.COM

Dr. Stefanie Morgan joins Dr. Robert Dudley from AgelessRx to discuss a #research paper she co-authored that was #published in Volume 17, Issue 4 of Aging, entitled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.” DOI - https://doi.org/10.18632/aging.206235 Corresponding author - Stefanie L. Morgan - stefanie@agelessrx.com Author interview - https://www.youtube.com/watch?v=2qlIiVh2OJs Video short - https://www.youtube.com/watch?v=z5j2nyK2HZ8 Abstract Design: This 48-week decentralized, double-blinded, randomized, placebo-controlled trial (NCT04488601) evaluated the long-term safety of intermittent low-dose rapamycin in a healthy, normative-aging human cohort. Participants received placebo, 5 mg or 10 mg compounded rapamycin weekly. The primary outcome measure was visceral adiposity (by DXA scan), secondary outcomes were blood biomarkers, and lean tissue and bone mineral content (by DXA scan). Established surveys were utilized to evaluate health and well-being. Safety was assessed through adverse events and blood biomarker monitoring. Results: Adverse and serious adverse events were similar across all groups. Visceral adiposity did not change significantly (ηp2 = 0.001, p = 0.942), and changes in blood biomarkers remained within normal ranges. Lean tissue mass (ηp2 = 0.202, p = 0.013) and self-reported pain (ηp2 = 0.168, p = 0.015) improved significantly for women using 10 mg rapamycin. Self-reported emotional well-being (ηp2 = 0.108, p = 0.023) and general health (ηp2 = 0.166, p = 0.004) also improved for those using 5 mg rapamycin. No other significant effects were observed. Conclusions: Low-dose, intermittent rapamycin administration over 48 weeks is relatively safe in healthy, normative-aging adults, and was associated with significant improvements in lean tissue mass and pain in women. Future work will evaluate benefits of a broader range of rapamycin doses on healthspan metrics for longevity, and will aim to more comprehensively establish efficacy. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206235 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, rapamycin, geroscience, longevity, healthspan To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Buffalo, NY — June 4, 2025 — The Longevity & Aging Series has been honored with the Silver Award for “Excellence in Video/Film” at the inaugural EPIC Awards celebration on May 29, 2025, during the Society for Scholarly Publishing (SSP) 47th Annual Meeting in Baltimore, Maryland. The EPIC Awards recognize the achievements of those who are advancing scholarly publishing through creativity, collaboration, and cutting-edge innovation. The Longevity & Aging Series, hosted by Aging (Aging-US) Editorial Board member Dr. Evgeniy Galimov, stood out for its impactful storytelling, production quality, and commitment to advancing understanding in the field of aging research. The Longevity & Aging Series brings together leading experts to discuss the latest developments in the biology of aging, healthy longevity, and interventions to improve healthspan. Now in its third season, the series is a trusted resource for scientists, clinicians, and the broader public interested in the future of aging research. For more information about the Aging (Aging-US) Longevity & Aging Series and to view the award-winning videos, please visit our show page or YouTube channel. If you are interested in becoming a guest or would like to know more about the series, please email us at media@impactjournals.com. Longevity & Aging Series Show Page - https://www.aging-us.com/longevity Aging-US YouTube Channel - https://www.youtube.com/@AgingJournal To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

BUFFALO, NY — June 4, 2025 — A new #editorial was #published in Aging (Aging-US) Volume 17, Issue 5, on May 29, 2025, titled “Rethinking healthcare through aging biology.” In this scientific editorial, Aging (Aging-US) Editor-in-Chief Marco Demaria from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG) and the University of Groningen (RUG), advocates for healthcare reform that addresses the biological drivers of aging rather than individual chronic conditions. The article proposes that targeting the root causes of age-related diseases through aging biology could revolutionize preventive care, extend healthspan, and reduce long-term healthcare costs. This proactive approach aligns with a growing body of aging research focused on improving healthy longevity. Dr. Demaria explains that today's disease-focused model is inadequate for aging populations, who often suffer from multimorbidity—the presence of multiple chronic illnesses like cancer, heart disease, and type 2 diabetes. These overlapping conditions, rooted in common aging mechanisms, overwhelm healthcare systems and lead to complex treatments with limited success. The editorial suggests that identifying and intervening in the biological aging process could prevent such diseases before they emerge. In the editorial, Dr. Demaria outlines three healthcare paradigms. The first is the existing system, which reacts to disease after symptoms appear. The second involves intervening once age-related damage begins, using new tools such as senolytics, which eliminate harmful senescent cells, and rapalogs, which regulate cellular metabolism. The third and most forward-looking model focuses on preventing aging-related damage before it starts. This strategy supports lifelong biological balance and seeks to avoid early molecular decline through continuous health maintenance. Prevention is key in this model. Lifestyle choices—such as exercise, a healthy diet, quality sleep, and stress reduction—play a vital role in slowing the aging process. Dr. Demaria also points to the promise of biological age diagnostics—tools or tests that estimate a person's biological age—which allow people to track their physiological aging and adopt personalized interventions. Additionally, optimizing maternal nutrition and early-life health can contribute to lifelong disease prevention. To support this shift, the editorial calls for major changes in medical education. Physicians must be trained in geroscience, healthspan optimization, and personalized preventive care. This knowledge will prepare future clinicians not just to treat disease, but to delay or prevent it altogether. Collaboration among healthcare providers, researchers, and policymakers will be essential for building this new system. ​​“The third paradigm—preventing aging-related damage—demands a systemic shift toward predictive and preventative research, with an emphasis on multi-omic data, lifestyle interventions, and early-life interventions.” By redefining medicine around the science of aging, Dr. Demaria's editorial highlights the path toward healthier aging, longer life expectancy, and a more sustainable healthcare future. DOI - https://doi.org/10.18632/aging.206262 Corresponding author - Marco Demaria - m.demaria@umcg.nl Video short - https://www.youtube.com/watch?v=xR-16cjHnQY To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — June 3, 2025 — A new #research paper was #published in Aging (Aging-US) on May 1, 2025, as the #cover of Volume 17, Issue 5, titled “Defining the hypoxic thresholds that trigger blood-brain barrier disruption: the effect of age.” In this study, researchers Arjun Sapkota, Sebok K. Halder, and Richard Milner from San Diego Biomedical Research Institute investigated how aging affects the brain's vulnerability to low oxygen, or hypoxia. Using C57BL/6J mice ranging from 2 to 23 months of age, they identified specific oxygen levels that disrupt the blood-brain barrier (BBB)—a critical structure that protects brain tissue from harmful substances. The findings are important for understanding age-related cognitive decline and the potential risks faced by individuals with chronic oxygen-limiting conditions such as asthma, sleep apnea, emphysema, and heart disease. The BBB is essential for maintaining brain health. In this study, mild and prolonged hypoxia—called chronic mild hypoxia—was found to compromise the BBB in mice. Older mice showed significantly more BBB disruption than younger ones. Notably, barrier weakening and blood vessel changes occurred at oxygen levels of just 15% in aged mice, compared to 13% in young mice. These data suggest that the aging brain is more sensitive to oxygen deprivation, even at levels that may be considered only mildly hypoxic. The researchers also determined when this vulnerability emerged. The BBB showed increased sensitivity to low oxygen not only in aged mice but also in mice as young as 2 to 6 months, with a second spike occurring between 12 and 15 months—equivalent to middle age in mice. These findings may reflect age-dependent changes in brain vascular function and remodeling capacity. “Hypoxia-induced endothelial proliferation was relatively constant across the age range, but advanced age strongly enhanced the degree of BBB disruption (4-6-fold greater in 23 months vs. 2 months old).” Another key focus was microglial activation, a sign of brain inflammation. Aged mice exhibited higher microglial activation across all oxygen levels, including normal conditions. Chronic microglial activation is closely linked to neuroinflammation and has been implicated in diseases such as Alzheimer's. While the rate of blood vessel formation was constant across ages, the degree of BBB disruption increased sharply with age, suggesting that repair mechanisms may weaken over time. These results may help explain why older adults with chronic hypoxia-related diseases are at higher risk for neurodegeneration and cognitive decline. The study also draws attention to the risks of high-altitude exposure for aging populations, where oxygen levels naturally drop. Altogether, these findings underscore the importance of protecting brain health in older individuals by managing oxygen exposure and reducing hypoxia-related risks. The researchers emphasize the need to develop new therapies that support blood-brain barrier integrity, particularly in aging populations exposed to chronic or intermittent low-oxygen conditions. DOI - https://doi.org/10.18632/aging.206241 Corresponding author - Richard Milner - rmilner@sdbri.org Video short - https://www.youtube.com/watch?v=Nr6rTm7aJRo Keywords - aging, blood-brain barrier integrity, endothelial, proliferation, microglia, chronic mild hypoxia, hypoxic threshold To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — May 23, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 1, 2025, titled “Examining frailty phenotypes of community-dwelling older adults in Taiwan using the falls risk for older people in the community – Taiwan version (Tw-FROP-Com).” A research team led by first author Ya-Mei Tzeng and corresponding authors Yu-Tien Chang and Yaw-Wen Chang from the National Defense Medical Center studied older adults in Taiwan and found that unintentional weight loss is the most significant individual predictor of fall risk among the common signs of frailty. This finding highlights the importance of early detection and tailored interventions to reduce fall-related injuries among aging populations. Falls are a major cause of injury-related death in seniors, especially in low- and middle-income countries. In Taiwan, they rank as the second leading cause of accidental death among those aged 65 and older. The researchers evaluated five signs of frailty—weakness, slowness, exhaustion, low physical activity, and unintentional weight loss—using a locally adapted fall risk screening tool, Tw-FROP-Com. Frailty is a condition marked by reduced strength, stamina, and resilience, making older adults more vulnerable to accidents and illness. The study analyzed data from 375 older adults participating in a fall prevention program in Keelung City. Of these, 18.7% were classified as frail, and nearly one-third had experienced a fall in the past year. All five frailty signs were associated with increased fall risk, but statistical analysis showed that unintentional weight loss had the strongest association, even after adjusting for factors like age and previous falls. Rather than relying on a broad frailty label, this study found that analyzing each frailty feature individually provided more accurate predictions of fall risk. Weight loss, in particular, was also associated with conditions such as malnutrition, muscle decline, or chronic illness. “Treating frailty as five distinct components provided a more precise prediction of fall risk than using a dichotomous frailty measure (Yes/No).” The findings support the use of accessible screening tools like Tw-FROP-Com in everyday healthcare settings. Because it does not require complex equipment or physical testing, it can be widely applied to identify older adults at risk. Interventions such as nutritional support, physical activity, and weight monitoring can then be offered before a fall occurs. The researchers recommend that public health programs and healthcare providers focus on each specific frailty sign, especially unintentional weight loss, rather than relying only on overall frailty status. As the global population ages, targeted fall prevention strategies like these may help older adults live healthier, more independent lives. Paper DOI: https://doi.org/10.18632/aging.206231 Corresponding authors: Yu-Tien Chang – greengarden720925@gmail.com; Yaw-Wen Chang- yawwenc@office365.ndmctsgh.edu.tw Keywords: aging, frailty, fall risk, fried frailty criteria, older adults, Tw-FROP-Com Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenetics, DNA methylation, diet, biological clock To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM