Aging-US

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

In a world where we are living longer but not always healthier, scientists are searching for ways to add life to our years, not just years to our lives. A recent study published in Aging (Aging-US), Volume 17, Issue 4, led by researchers at the National University of Natural Medicine, suggests that certain common foods, already known for their health benefits, might also help slow or even reverse epigenetic or biological aging. These foods, rich in specific plant compounds, appear to influence our DNA in ways that may slow down the body's epigenetic clock. Full blog - https://aging-us.org/2025/05/study-identifies-foods-that-may-reverse-biological-age-and-promote-healthy-aging-in-men/ Paper DOI - https://doi.org/10.18632/aging.206240 Corresponding author - Ryan Bradley - rbradley@nunm.edu Video short - https://www.youtube.com/watch?v=T6I33AIAIFM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206240 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

BUFFALO, NY — May 20, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 17, 2025, titled “Dietary associations with reduced epigenetic age: a secondary data analysis of the methylation diet and lifestyle study.” In this study, researchers led by first author Jamie L. Villanueva from the University of Washington and the National University of Natural Medicine, along with corresponding author Ryan Bradley from the National University of Natural Medicine and University of California, investigated how diet influences epigenetic aging. They found that certain plant-based foods containing natural compounds called methyl adaptogens were associated with a decrease in epigenetic age. This effect was measured using DNA methylation, a marker that reflects how the body ages at the cellular level. The findings suggest that targeted food choices may help slow the aging process. Epigenetic age refers to how old a person's cells appear biologically, rather than their actual age in years. DNA methylation patterns, which are chemical tags on DNA, can indicate whether someone is aging faster or slower than expected. For this study, researchers used Horvath's epigenetic clock, a widely accepted tool, to measure changes in epigenetic age. The analysis included healthy men aged 50 to 72 who had previously completed an eight-week program featuring a plant-based, nutrient-rich diet, along with guidance on exercise, sleep, and stress management. Researchers focused on individual dietary differences to understand why some participants experienced greater improvements in epigenetic age than others. The study found that those who ate higher amounts of methyl adaptogen foods—including turmeric, rosemary, garlic, berries, green tea, and oolong tea—experienced greater reductions in epigenetic age. These benefits remained significant even after accounting for weight changes and participants' starting epigenetic age, suggesting that the foods themselves had a direct impact on aging markers. “In hierarchical linear regression, foods investigated as polyphenolic modulators of DNA methylation (green tea, oolong tea, turmeric, rosemary, garlic, berries) categorized in the original study as methyl adaptogens showed significant linear associations with epigenetic age change (B = -1.21, CI = [-2.80, -0.08]), after controlling for baseline epigenetic age acceleration and weight changes.” The natural compounds in methyl adaptogen foods are known to influence how genes behave by affecting DNA methylation. Previous studies have shown that these compounds may support healthy aging and help lower the risk of conditions such as heart disease and cognitive decline. While this study involved a relatively small group of middle-aged men, it adds knowledge to growing global research showing that diets rich in polyphenols—found in vegetables, fruits, and teas—are associated with slower aging. These findings support earlier results from studies on Mediterranean and traditional Japanese diets, both known for their health benefits. Future research should include larger and more diverse populations and use updated epigenetic aging tools to confirm these results. Based on current evidence, this study highlights a practical, food-based strategy that may help reduce epigenetic aging and support long-term health. DOI - https://doi.org/10.18632/aging.206240 Corresponding author - Ryan Bradley - rbradley@nunm.edu To learn more about the journal, 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

In this #episode of the Longevity & Aging Series, Dr. Shubhankar Suman from the Department of Oncology at Georgetown University Medical Center joins host Dr. Evgeniy Galimov to discuss a #research paper he co-authored in Volume 17, Issue 1 of Aging (Aging-US), titled: “Senolytic agent ABT-263 mitigates low- and high-LET radiation-induced gastrointestinal cancer development in Apc1638N/+ mice.” DOI - https://doi.org/10.18632/aging.206183 Corresponding author - Shubhankar Suman - ss2286@georgetown.edu Author interview - https://www.youtube.com/watch?v=ClLO0ERwC0M Video short - https://www.youtube.com/watch?v=M_WEht4vy4w Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206183 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence-associated secretory phenotype, senolytic agent, carcinogenesis, inflammation, β-catenin To learn more about Aging (Aging-US), 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 14, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 10, 2025, titled “Impact of Factor Xa inhibitors on cardiovascular events in older patients with nonvalvular atrial fibrillation.” In this study, first author Masahiko Takahashi and corresponding author Keisuke Okawa led a research team from Kagawa Prefectural Central Hospital and Hyogo Medical University that investigated whether Factor Xa inhibitors (Xa-Is)—a type of blood thinner—can reduce the risk of heart-related complications in patients over 80 with nonvalvular atrial fibrillation (NVAF). The study found that patients using Xa-Is experienced significantly fewer cardiovascular problems than those on other anticoagulants. This finding is especially relevant, as older adults face a high risk of both stroke and heart disease. Atrial fibrillation is a common heart rhythm disorder, particularly in the elderly, that increases the risk of blood clots, heart failure, and stroke. Anticoagulants are often prescribed to prevent clots, but not all types have the same effects on heart health. This study focused on comparing Xa-Is—specifically rivaroxaban, apixaban, and edoxaban—with commonly used drugs such as warfarin and dabigatran. Researchers followed more than 1,000 patients aged 80 and above for up to five years to assess the long-term impact of these medications on cardiovascular outcomes. Patients who used Xa-Is had significantly lower rates of heart failure, artery disease, and cardiovascular death. The risk of cardiovascular problems in the Xa-I group was less than half that of those on non-Xa-I medications. These benefits remained even after adjusting for factors like age, existing heart conditions, and kidney function. Additionally, stroke and all-cause death rates were notably lower in the Xa-I group. “Xa-Is may be useful for not only anticoagulation but also the prevention of cardiovascular events in very old patients with NVAF.” What makes Xa-Is different, according to the researchers, is their ability to inhibit a specific biological pathway—known as Factor Xa–PAR2—that contributes to inflammation, fibrosis, and damage in blood vessels and heart tissue. This effect extends beyond their traditional role in preventing blood clots. Although the study was conducted at a single medical center in Japan, its rigorous design and long follow-up period enhance the reliability of the findings for real-world clinical decision-making. While further studies, especially across multiple centers, are needed to confirm the full range of benefits, this study strongly suggests that Xa-Is may offer broader cardiovascular protection for very old patients. The findings could influence how clinicians choose blood thinners for elderly individuals with atrial fibrillation, potentially improving both survival and quality of life in this growing population. DOI - https://doi.org/10.18632/aging.206238 Corresponding author - Keisuke Okawa - k-ookawa@chp-kagawa.jp Video short - https://www.youtube.com/watch?v=YtbYpfVDVDI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206238 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Factor Xa inhibitor, atrial fibrillation, older patient, cardiovascular events 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

Werner syndrome is a rare condition marked by accelerated aging. A recent study, featured as the cover paper in Aging (Aging-US), Volume 17, Issue 4, led by researchers at the University of Oslo and international collaborators, suggests that nicotinamide adenine dinucleotide (NAD+), a vital molecule involved in cellular energy production, may be key to understanding this disease and developing future strategies to manage it. Understanding Werner Syndrome Werner syndrome (WS) is a rare genetic condition that causes people to age more quickly than normal. By their 20s or 30s, individuals with WS often show signs typically associated with older age, such as cataracts, hair loss, thinning skin, and heart disease. This premature aging is caused by mutations in the WRN gene, which normally helps repair DNA and protect cells from damage. While the WRN gene's role in maintaining genetic stability is well understood, the reasons behind the rapid decline of cells in WS patients are still not fully clear. The Study: Investigating NAD+ in Werner Syndrome Nicotinamide adenine dinucleotide levels naturally decline with age. In the study titled “Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation,” researchers investigated whether this decline is more severe in people with WS and whether restoring NAD+ levels could help slow the aging process in these patients. Full blog - https://aging-us.org/2025/05/fighting-premature-aging-how-nad-could-help-treat-werner-syndrome/ Paper DOI - https://doi.org/10.18632/aging.206236 Corresponding author - Evandro F. Fang - e.f.fang@medisin.uio.no Video short - https://www.youtube.com/watch?v=WpRpi8TYPfU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206236 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Werner syndrome, premature aging, NAD+, mitochondria, proliferation 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 13, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 7, 2025, titled “Pharmacological recapitulation of the lean phenotype induced by the lifespan-extending sulfur amino acid-restricted diet.” In this study, the research team, led by first author Naidu B. Ommi and corresponding author Sailendra N. Nichenametla from the Orentreich Foundation for the Advancement of Science Inc., investigated whether the drug buthionine sulfoximine (BSO) could replicate the effects of sulfur amino acid restriction (SAAR), a challenging diet known to reduce obesity. The study found that BSO produced similar reductions in fat mass and weight gain. This drug-based approach may offer a simpler and safer treatment for obesity, especially for those unable to follow strict dietary plans. Obesity and metabolic disorders raise the risk of chronic illnesses like heart disease, diabetes, and Alzheimer's disease. While SAAR, a diet low in the amino-acids methionine and cysteine, has shown powerful health benefits in animal studies, its translation to humans has been limited by adherence challenges. This new study explored whether BSO, a compound that lowers glutathione (GSH) levels in the body, could mimic SAAR's effects without dietary restriction. Researchers tested four groups of obese mice on high-fat diets. One group received the SAAR diet, another was given a regular diet plus BSO, while two control groups received either no treatment or a supplement that increased GSH levels. The BSO-treated mice showed lower fat mass, reduced liver fat, and prevented weight gain, results comparable to those on the SAAR diet. These benefits occurred without reducing food intake or muscle mass, making BSO a particularly promising treatment option. “BSO mice exhibited all SAAR-induced changes, with two notable differences, i.e., a smaller effect size than that of the SAAR diet and a higher predilection for molecular changes in kidneys than in the liver.” Additional findings revealed that both the SAAR diet and BSO influenced metabolic activity by activating pathways related to fat storage, but they did so in different organs. The SAAR diet had stronger effects in the liver, while BSO acted more in the kidneys. Both interventions increased levels of the amino acid serine, which is associated with lower fat production. Unlike many obesity treatments that suppress appetite or reduce muscle, BSO helped prevent fat accumulation while preserving lean mass and food consumption. No signs of liver or kidney toxicity were observed during the 13-week study, suggesting the drug's safety at the tested dose. Since BSO has previously been evaluated in human clinical trials for other conditions, repurposing it for metabolic diseases may be relatively straightforward. However, the researchers point out that there should be further studies in both animals and humans. If successful, this strategy could provide a practical alternative to difficult-to-maintain diets and help more people manage weight long-term. DOI: https://doi.org/10.18632/aging.206237 Corresponding author: Sailendra N. Nichenametla – snichenametla@orentreich.org Video short - https://www.youtube.com/watch?v=AcCzYTIElGY Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords: aging, buthionine sulfoximine, thiols, serine, anti-obesity drugs 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 — May 7, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 4, 2025, titled “Influence of rapamycin on safety and healthspan metrics after one year: PEARL trial results.” A research team led by first author Mauricio Moel and corresponding author Stefanie L. Morgan from AgelessRx conducted a clinical trial to determine whether low-dose, intermittent rapamycin could safely improve healthspan in older adults. The findings suggest rapamycin may offer measurable benefits for physical function and overall well-being, reinforcing its potential as a safe intervention to support healthy aging. Aging remains the leading cause of chronic conditions such as heart disease, diabetes, and dementia. While medical advances have extended lifespan, many people still experience declining health and reduced mobility in later years. This growing gap between lifespan and healthspan has driven interest in therapies that target aging itself. Rapamycin, an FDA-approved drug originally used in transplant medicine, has drawn attention for its ability to influence aging-related pathways in animal studies. Until recently, its safety and benefits in healthy human populations were largely unknown. The PEARL trial is the longest study so far to explore rapamycin's use for longevity in healthy aging adults. Researchers followed 114 participants aged 50 to 85 over 48 weeks in a randomized, double-blind, placebo-controlled design. Participants received either a placebo or 5 mg or 10 mg of compounded rapamycin once per week. The study's primary goal was to measure changes in visceral fat, while secondary outcomes included lean muscle mass, blood markers, and quality-of-life assessments. The trial found that low-dose rapamycin was safe and well-tolerated, with serious side effects reported at similar rates across all groups. The most frequent minor issue among rapamycin users was mild gastrointestinal discomfort. While no significant reductions in visceral fat were observed, women taking 10 mg of rapamycin showed significant gains in lean muscle and reported reduced pain. In addition, participants taking 5 mg weekly reported improvements in emotional well-being and general health, as measured by validated surveys. “Our findings provide evidence that these rapamycin regimens are well tolerated with minimal adverse effects when administered for at least one year within normative aging individuals.” Researchers noted some limitations, including the relatively small and health-conscious participant group, which may have limited the ability to detect larger effects. The compounded form of rapamycin used also had lower absorption than commercial versions, possibly reducing its impact. Overall, the PEARL trial provides early clinical evidence that low-dose rapamycin may help support physical and emotional well-being in older adults. Further studies with larger and more diverse populations will be essential to confirm the study results and refine dosing strategies for broader application. DOI: https://doi.org/10.18632/aging.206235 Corresponding author: Stefanie L. Morgan – stefanie@agelessrx.com Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords: rapamycin, aging, healthspan, longevity, geroscience 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 — May 6, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 4, on April 2, 2025, titled “Fisetin ameliorates vascular smooth muscle cell calcification via DUSP1-dependent p38 MAPK inhibition.” In this study, researchers at Johannes Kepler University Linz found that fisetin, a natural substance found in fruits and vegetables, helps protect blood vessels from hardening, which is a common problem in older adults and people with kidney disease. This discovery highlights fisetin's potential to prevent vascular calcification and reduce cardiovascular damage caused by aging and chronic kidney disease. The research, led by first author Mehdi Razazian and corresponding author Ioana Alesutan, focused on vascular calcification—a condition in which blood vessels stiffen due to calcium deposits. This process is common in aging and chronic kidney disease and increases the risk of heart attacks and strokes. Using human and mouse study models, the researchers tested fisetin's ability to prevent this calcification in vascular smooth muscle cells (VSMC), which play a key role in maintaining vessel health. Fisetin, known for its anti-inflammatory and antioxidant properties, significantly reduced calcium buildup and calcification markers under stress conditions that mimic disease. The team also discovered that fisetin suppresses activity in a signaling pathway called p38 MAPK, which is known to promote calcification. This effect depends on a protein called DUSP1. When DUSP1 was blocked, fisetin could no longer protect the cells, showing that this protein is essential for its anti-calcification activity. The researchers confirmed fisetin's protective effects in isolated mouse arteries and in living mice treated with high doses of vitamin D, which typically increases arterial calcification. “Mechanistically, fisetin requires the phosphatase DUSP1 to inhibit p38 MAPK in order to mediate its protective effect on VSMC calcification.” Importantly, the researchers tested fisetin under conditions similar to human disease. When VSMCs were exposed to blood serum from kidney dialysis patients—a condition known to trigger vascular calcification—fisetin again reduced calcium buildup and protected the cells. These findings suggest fisetin could be useful in countering the harmful vascular effects seen in chronic kidney disease. This study adds to growing evidence that fisetin may protect blood vessels from aging-related damage. While more research is needed before it can be used in clinical treatments, the study highlights fisetin as a promising candidate for slowing or preventing vascular calcification. The findings could have broad implications for aging populations and individuals with kidney disease, who are at greater risk for heart problems due to vascular stiffening. Read the full paper: DOI: https://doi.org/10.18632/aging.206233 Corresponding author: Ioana Alesutan – ioana.alesutan@jku.at Keywords: aging, vascular calcification, vascular smooth muscle cells, fisetin, dual-specificity phosphatase 1, p38 MAPK ______ 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 5, 2025 – Aging (Aging-US), #published by Impact Journals, is pleased to #announce its participation at the upcoming Society for Scholarly Publishing (SSP) 47th Annual Meeting. The #event will take place from May 28-30, 2025, in Baltimore, Maryland. Attendees are invited to visit Booth No. 209 to meet members of the Aging (Aging-US) team. The 2025 meeting theme, “Reimagining the Future of Scholarly Publishing at the Intersection of Value and Values,” underscores the urgency of adapting to rapid technological change, including AI, and addressing growing concerns around research integrity and trust. These priorities align closely with our mission to foster open, reliable, and impactful scientific communication in the field of aging and age-related diseases. In addition, the Longevity & Aging Series - hosted by Dr. Evgeniy Galimov and presented by Aging (Aging-US) - is a Finalist for a Society for Scholarly Publishing (SSP) 2025 EPIC Award in the Video/Film category. Winners will be announced at the EPIC Awards Celebration on May 29. We look forward to connecting with SSP 2025 attendees to share more about Aging (Aging-US) and our publishing initiatives. 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

Aging (Aging-US) invites #submissions for a Special Collection dedicated to the theme of cellular #senescence, spanning its basic mechanisms, physiological and pathological functions, and clinical applications. This collection is published in memory of Professor Judith Campisi, a pioneering force in the field of cellular senescence whose groundbreaking work shaped the understanding of senescence in aging, cancer, and tissue homeostasis. Her legacy continues to inspire generations of scientists working to decode the complex biology of senescent cells and their impact on health and disease. We welcome original research articles, reviews, and perspectives on topics including: -Fundamental mechanisms of senescence induction and maintenance -Regulation and context-specific roles of the senescence-associated secretory phenotype (SASP) -Beneficial and detrimental effects of senescent cells in vivo -Senescence in development, aging, regeneration, and age-related diseases -Biomarkers, imaging, and tools for senescence detection and quantification -Therapeutic targeting of senescent cells: senolytics, senomorphics, and clinical translation This Special Collection is guest edited by Han Li and Irina Conboy, both internationally recognized leaders in the study of senescence and aging. Submission Details: -Submission Deadline: January 15, 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

BUFFALO, NY — May 1, 2025 — A new #research paper was #published in Aging (Aging-US) on April 2, 2025, as the #cover of Volume 17, Issue 4, titled “Decreased mitochondrial NAD+ in WRN deficient cells links to dysfunctional proliferation.” In this study, the team led by first author Sofie Lautrup and corresponding author Evandro F. Fang, from the University of Oslo and Akershus University Hospital in Norway, discovered that cells from people with Werner syndrome (WS)—a rare genetic disorder that causes premature aging—have low levels of a molecule called NAD+ in their mitochondria. This molecule is essential for energy production, cellular metabolism, and maintaining cell health. The researchers also found a potential way to improve cell function in WS patients, pointing to new directions for treating age-related decline and other premature aging disorders. Werner syndrome leads to signs of aging much earlier than normal, including problems such as cataracts, hair loss, and atherosclerosis by age 20 to 30. The team found that when the WRN gene is missing or damaged, cells cannot maintain healthy NAD+ levels in their mitochondria. As a result, the cells age more quickly and stop growing properly. When the researchers boosted NAD+ levels using nicotinamide riboside (a vitamin B3 compound) the affected stem cells and skin cells from patients showed less aging and improved mitochondrial activity. “Interestingly, only 24 h treatment with 1 mM nicotinamide riboside (NR), an NAD+ precursor, rescued multiple pathways in the WRN−/− cells, including increased expression of genes driving mitochondrial and metabolism-related pathways, as well as proliferation-related pathways.” The study also found that the WRN gene helps regulate other important genes that control how NAD+ is made in the body. Without WRN, this system becomes unbalanced, which affects how cells function, grow, and respond to stress. Although adding more NAD+ helped some cells look healthier, it could not completely fix the growth problems in other types of lab-grown cells. This suggests that while NAD+ supplementation is beneficial, it cannot fully replace the essential functions of the WRN gene. These findings offer new insights into the biological mechanisms of aging and reinforce the therapeutic potential of targeting NAD+ metabolism in age-related and genetic diseases. Future studies will aim to better understand how subcellular NAD+ regulation interacts with mutations like those seen in WS. Finally, this research supports ongoing efforts to develop NAD+-based treatments that could slow cellular aging and improve quality of life for patients with premature aging conditions. DOI - https://doi.org/10.18632/aging.206236 Corresponding author - Evandro F. Fang - e.f.fang@medisin.uio.no Video short - https://www.youtube.com/watch?v=WpRpi8TYPfU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206236 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Werner syndrome, premature aging, NAD+, mitochondria, proliferation 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 — April 29, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 20, 2025, titled “Inhibition of the metalloprotease ADAM19 as a novel senomorphic strategy to ameliorate gut permeability and senescence markers by modulating senescence-associated secretory phenotype (SASP).” Researchers, led by first author Sudipta Bar and corresponding authors Amit Sharma and Pankaj Kapahi from the Buck Institute for Research on Aging, have found that the enzyme ADAM19 plays an important role in regulating aging in cells and inflammation in the gut. Their study shows that blocking ADAM19 reduced gut damage and inflammation in fruit flies, mice, and human cells. This discovery points to a new possible way to treat gut disorders related to aging by reducing the harmful signals from senescent (aging) cells. As individuals age, DNA damage can lead to the accumulation of senescent cells, contributing to tissue damage. These are cells that stop dividing and release harmful inflammatory substances called the senescence-associated secretory phenotype (SASP). In this study, researchers used fruit flies to search for genes involved in radiation-related gut damage. They identified a gene called meltrin, which is similar to human ADAM19. When meltrin was turned off, the flies had less gut leakage, less inflammation, and fewer signs of cellular aging. “Through an unbiased genome-wide association study (GWAS) utilizing 156 strains from the Drosophila Genetic Reference Panel (DGRP), we identified meltrin (the drosophila orthologue of mammalian ADAM19) as a potential modulator of the senescence-associated secretory phenotype (SASP).” To test if these results applied beyond flies, the team inhibited ADAM19 in mice using a drug called batimastat. Mice treated with the drug after chemotherapy exposure had stronger gut barriers and lower levels of inflammatory markers. The findings extended to human cell cultures, where ADAM19 inhibition reduced signs of cellular aging, including the expression of SASP proteins and β-galactosidase, a classic aging marker. Importantly, this approach does not kill aging cells like many 'senolytic' therapies but instead reduces the harmful substances they release, making it a potential "senomorphic" strategy. The study also showed that ADAM19 helps release certain SASP proteins by cutting them at the cell surface, suggesting a direct role in regulating inflammatory signals. Through proteomic analysis, the team identified 12 SASP proteins that were significantly reduced when ADAM19 was blocked. Many of these proteins are linked to inflammation, immune response, and tissue remodeling in diseases such as inflammatory bowel disease and Crohn's disease. This connection underlines the relevance of the findings for treating chronic gut disorders in aging populations. By targeting ADAM19, researchers may have found a new way to protect gut health and lower inflammation caused by aging cells. This study offers a promising path for creating treatments that maintain healthy tissues without having to destroy aging cells, which could benefit people with gut damage related to aging or medical treatments. DOI - https://doi.org/10.18632/aging.206224 Corresponding authors - Amit Sharma - amit.sharma@sens.org, and Pankaj Kapahi - pkapahi@buckinstitute.org Video short - https://www.youtube.com/watch?v=dRfxQ20O2fQ 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​​. MEDIA@IMPACTJOURNALS.COM

In this #episode of the Longevity & Aging Series, Dr. Stephen Vatner from the Department of Cell Biology and Molecular Medicine at Rutgers New Jersey Medical School, joins host Dr. Evgeniy Galimov to discuss a #research perspective he co-authored in Volume 16, Issue 22 of Aging (Aging-US), titled “Brown adipose tissue enhances exercise performance and healthful longevity.” DOI - https://doi.org/10.18632/aging.206179 Corresponding author - Stephen F. Vatner - vatnersf@njms.rutgers.edu Author interview - https://www.youtube.com/watch?v=-DE4H2DtSZg Video short - https://www.youtube.com/watch?v=n1DvuR7owJQ Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206179 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, brown adipose tissue, white adipose tissue, healthful longevity, exercise, regulator of G protein signaling 14 To learn more about Aging (Aging-US), 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/ Pinterest - https://www.pinterest.com/AgingUS/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Aging (Aging-US) was proud to sponsor the Muscle Aging Science & Translation (MAST) Symposium, organized by the Aging Initiative at Harvard University on Friday, April 18, 2025. This important event brought together 350 participants—chosen from more than 1,300 applicants—including students, researchers, company founders, investors, and industry leaders. Together, they explored the latest research and innovations in muscle health and aging. The symposium reflected the journal's strong commitment to supporting collaboration across fields and advancing research in aging. -Key Highlights from the MAST Symposium- Clinical Research Perspectives on Frailty The symposium opened with a strong clinical session led by experts from top institutions: Dr. Roger Fielding (Tufts University and Boston Claude D. Pepper Older Americans Independence Center) and Drs. Douglas Kiel, Shivani Sahni, and Yi-Hsiang Hsu (Harvard Medical School and Beth Israel Deaconess Medical Center). The panel discussed key topics such as the biology of frailty, how bone and muscle health are connected, and the influence of genetics, diet, and exercise on staying strong as we age. By blending real-life patient care with the latest research, the speakers shed light on the challenges of sarcopenia—the gradual loss of muscle strength and mass that occurs with age—and the new scientific approaches being developed to improve treatment. Full recap - https://aging-us.org/2025/04/agings-ongoing-support-for-scientific-innovation-sponsoring-the-muscle-aging-science-translation-symposium/ 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 23, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 18, 2025, titled “Epigenetic and accelerated age in captive olive baboons (Papio anubis), and relationships with walking speed and fine motor performance.” In this study, led by Sarah J. Neal from The University of Texas MD Anderson Cancer Center, researchers examined how the epigenetic age of baboons—a measure of biological aging based on DNA methylation—compared to their actual age (chronological age) and whether it related to signs of aging like slower walking or reduced hand coordination. While many baboons showed a mismatch between their epigenetic and chronological ages, these differences did not consistently align with physical performance measures. Researchers analyzed blood samples from 140 captive olive baboons (Papio anubis) to determine whether these primates, like humans, show signs of “age acceleration”—a condition where epigenetic age surpasses chronological age. The results revealed that about a quarter of the baboons exhibited accelerated aging, while another quarter showed signs of slower aging, known as “age deceleration.” “We found that epigenetic age was strongly correlated with chronological age, and that approximately 27% of the sample showed age acceleration and 28% showed age deceleration." The scientists then investigated whether these differences were reflected in physical indicators such as walking speed or fine motor skills. To do this, researchers measured walking speed by tracking how quickly baboons moved between points in their enclosures and assessed fine motor skills using a simple task that involved picking up small objects. Older baboons did tend to walk more slowly and perform worse on tasks requiring dexterity, patterns also seen in aging humans. However, these changes were more closely related to chronological age than epigenetic age. Two different methods were used to measure the gap between epigenetic and chronological age. Each method produced slightly different outcomes, highlighting the complexity of defining age acceleration. In one analysis, the oldest baboons appeared to age more slowly epigenetically, possibly reflecting selective survival, where only the healthiest individuals live into old age. This research is among the first to classify baboons based on their epigenetic aging rate and investigate how this links to real-world signs of aging. Although the findings did not provide clear evidence that epigenetic age acceleration leads to physical decline, they point to the importance of DNA methylation as a biomarker in aging research. Because baboons share many biological similarities with humans, these findings help refine how researchers measure aging and assess potential early warning signs of decline. Continued studies in baboons and other primates may improve our understanding of how epigenetic aging influences health and longevity—and could help develop better tools for predicting age-related decline in humans. DOI - https://doi.org/10.18632/aging.206223 Corresponding author - Sarah Neal - SJNeal@MDAnderson.org Video short - https://www.youtube.com/watch?v=EFfRMFbAMqk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206223 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 21, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 14, 2025, titled “Effects of a natural ingredients-based intervention targeting the hallmarks of aging on epigenetic clocks, physical function, and body composition: a single-arm clinical trial.” A team of researchers, led by first authors Natalia Carreras-Gallo and Rita Dargham, and corresponding author Varun B. Dwaraka from TruDiagnostic, studied how a natural anti-aging supplement called the Cel System might influence the aging process. They found that participants who took the supplement for one year showed a reduction in biological age, along with improved muscle strength and body composition. The study highlights the potential of lifestyle and nutritional supplements to support healthy aging. “The Cel System supplement range was formulated to target pathways associated with the Hallmarks of Aging when combining Cel1, Cel2, and Cel3 formulas.” Cel System is a natural supplement made from a mix of plant compounds, vitamins, and antioxidants designed to target the biological mechanisms associated with aging. Over the course of a year, 51 adults between the ages of 54 and 84 participated in the clinical trial. The group included 26 men and 25 women. Researchers tracked changes in biological age using DNA-based tests known as epigenetic clocks, along with physical performance and body composition metrics. Participants were also encouraged to walk for 10 minutes and practice mindfulness for five minutes daily. Results showed that participants experienced improvements in grip strength, lower body mobility, and reductions in body weight, waist circumference, and body mass index. These physical gains were supported by slower biological aging, as measured by multiple epigenetic clocks. In addition, the supplement appeared to reduce stem cell turnover, a key marker of aging at the cellular level. The study also reported changes in immune cell composition, suggesting that the supplement may help regulate immune function as people age. Biomarkers associated with liver function also shifted, pointing to potential improvements in organ health. However, levels of inflammation markers did not significantly change. Analysis of methylation chemical marks on DNA revealed that the supplement influenced gene activity related to stress response, brain function, and cell communication. These molecular-level changes may help explain the broader benefits seen in physical and biological aging measures. Although this was a pilot study without a control group, the findings suggest that the Cel System supplement shows potential for reducing signs of aging and improving overall health. The authors suggest future randomized controlled trials with larger sample sizes to confirm these results and explore the supplement's long-term effects on longevity. This study adds to growing evidence that targeted natural supplements may slow biological aging and extend healthspan. By combining epigenetic analysis with real-world health data, the findings offer new insight into how nutraceuticals, like Cel System, could promote long-term health and resilience. Paper: DOI: https://doi.org/10.18632/aging.206221 Corresponding author: Varun B. Dwaraka – varun.dwaraka@trudiagnostic.com Keywords: aging, epigenetic age change, physiological age change, epigenetic biomarker proxies, hallmarks of aging, nutraceutical longevity interventions To learn more about the journal, please visit our website at www.Aging-US.com​​ and connect with us on social media at: Facebook - www.facebook.com/AgingUS/ X - twitter.com/AgingJrnl Instagram - www.instagram.com/agingjrnl/ YouTube - www.youtube.com/@AgingJournal LinkedIn - www.linkedin.com/company/aging/ Pinterest - www.pinterest.com/AgingUS/ Spotify - open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 16, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 12, 2025, titled “DNA methylation entropy is a biomarker for aging.” Researchers Jonathan Chan, Liudmilla Rubbi, and Matteo Pellegrini from the University of California, Los Angeles, led a study that discovered a new way to measure changes in DNA that can help predict a person's age. This method focuses on how random certain chemical tags on DNA become over time. The team compared this new measurement, called methylation entropy, to existing methods and found it performed just as well—or even better. These findings support the idea that changes in our epigenetic information are closely linked to aging and could offer new tools for studying age-related diseases. The study focused on DNA methylation, a process where chemical marks are added to DNA and help control which genes are turned on or off. Scientists have traditionally measured average methylation levels to estimate biological age using “epigenetic clocks.” This study, however, takes a different approach. The researchers used buccal swabs (cells from inside the cheek) from 100 individuals between ages 7 and 84 and applied targeted bisulfite sequencing techniques to measure methylation entropy across 3,000 regions of the genome. Entropy in this context reflects how disordered or varied the methylation patterns are at certain sites on the DNA. The researchers discovered that as people age, the entropy of methylation at many locations changes in a reproducible way. Sometimes it increases, reflecting more random patterns, and sometimes it decreases, showing more uniformity. These shifts are not always tied to how much methylation is happening, which suggests entropy provides new information beyond what traditional methods can offer. To test how well this new metric could predict age, the team used both statistical and machine learning models. They found that methylation entropy predicted age as accurately as traditional methods, and the best results came from combining entropy with other measurements like average methylation and a method called CHALM. These combined models were able to estimate age with an average error of just five years. "[...] methylation entropy is measuring different properties of a locus compared to mean methylation and CHALM, and that loci can become both more or less disordered with age, independently of whether the methylation is increasing or decreasing with age." This research supports the growing theory that aging is partly caused by a gradual loss of epigenetic information—the biological “instructions” that help keep our cells working properly. This insight also connects with recent studies suggesting that restoring this lost information might reverse some signs of aging. While more research is needed to study methylation entropy in other tissues, this work points to a more precise and powerful way to measure biological aging, which could influence the future of aging-related treatments and therapies. Read the full paper: DOI: https://doi.org/10.18632/aging.206220 Corresponding author: Matteo Pellegrini - matteope@gmail.com Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206220 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords: entropy, DNA methylation, aging, epigenetics, epigenetic clocks 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Breast cancer survivors are living longer than ever, thanks to research and medical advances, but new studies suggest that some treatments may come with a hidden cost: accelerated aging. A recent study, titled “Accelerated aging associated with cancer characteristics and treatments among breast cancer survivors,” published in Aging (Aging-US), reveals that breast cancer and its treatments may speed up biological aging, with effects lasting up to a decade post-diagnosis. Breast Cancer and Aging Breast cancer is one of the most common cancers among women worldwide. Medical advancements have dramatically improved survival rates, making it one of the most treatable forms of cancer. Yet, many survivors report lasting symptoms like fatigue, memory issues, and reduced vitality that resemble accelerated aging. This pattern has led scientists to investigate whether treatments for breast cancer might be contributing to biological age acceleration. Full blog - https://aging-us.org/2025/04/breast-cancer-treatments-hidden-impact-accelerated-aging-among-survivors/ Paper DOI - https://doi.org/10.18632/aging.206218 Corresponding author - Xiao-Ou Shu - xiao-ou.shu@vumc.org Video short - https://www.youtube.com/watch?v=cfuyzVyDeHY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206218 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, accelerated aging, PhenoAge, breast cancer, survivors 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 14, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 4, 2025, titled “Deciphering age-related transcriptomic changes in the mouse retinal pigment epithelium.” The study, led by first authors Sushil K. Dubey and Rashmi Dubey with corresponding author Mark E. Kleinman from East Tennessee State University, reveals that aging causes inflammation, oxidative stress, and gene disruption in the retinal pigment epithelium (RPE), a vital layer of cells in the eye. These changes may explain why older adults are more vulnerable to age-related eye diseases. The researchers also developed a human cell model to study retinal aging and test future therapies. The RPE plays a key role in maintaining retinal health. It recycles light-sensitive molecules, supports the visual cycle, and protects the retina from damage. When this layer becomes damaged, vision problems such as age-related macular degeneration can develop. In this study, researchers compared gene activity in RPE cells from young and aged mice. They found that aging increased the activity of genes involved in immune system responses, inflammation, and oxidative stress, three known triggers of tissue damage. At the same time, genes related to vision and light detection became less active, weakening the RPE's ability to support healthy vision. To reinforce these findings, the research team also aged human RPE cells in the lab. Over time, these cells showed the same patterns: inflammation increased, while genes tied to visual function decreased. This human cell model offers a practical way to explore how RPE degeneration happens over time and how it might be slowed down or reversed. The research also identified “hub genes,” which are central players of the gene networks involved in RPE aging. These are connected to immune signaling, oxidative damage, and changes in the eye's structural support. Many of these genes are already known to be involved in age-related retinal degeneration, so they may become important targets for future treatments aimed at protecting vision in older adults. “GO annotation of downregulated genes included processes related to visual perception, sensory perception of light stimulus, detection of light stimulus, detection of visible light, detection of external stimulus, detection of abiotic stimulus, phototransduction, cellular response to interferon-beta, response to interferon-beta, and response to light stimulus.” By mapping how the RPE changes with age at the molecular level, this study provides a clearer understanding of why aging leads to eye disease. It also introduces a reliable laboratory model that researchers can use to test new therapies. Altogether, the work is a key step toward developing treatments to slow or prevent vision loss tied to retinal aging. Read the full paper: DOI: https://doi.org/10.18632/aging.206219 Corresponding author: Mark E. Kleinman- kleinman@etsu.edu Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords: aging, transcriptome, retinal pigment epithelium, oxidative stress, inflammation, chronological 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

Paula Cilleros-Holgado from Pablo de Olavide University discusses a #research paper she co-authored that was #published in Volume 17, Issue 2 of Aging (Aging-US), entitled “Mitochondrial dysfunction, iron accumulation, lipid peroxidation, and inflammasome activation in cellular models derived from patients with multiple sclerosis.” DOI - https://doi.org/10.18632/aging.206198 Corresponding author - José Antonio Sánchez-Alcázar - jasanalc@upo.es Video interview - https://www.youtube.com/watch?v=wIV0lAHPA_M Abstract Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Despite advancements in managing relapsing active illness, effective treatments for the irreversible progressive decline in MS remain limited. Research employing skin fibroblasts obtained from patients with neurological disorders revealed modifications in cellular stress pathways and bioenergetics. However, research using MS patient-derived cellular models is scarce. In this study, we collected fibroblasts from two MS patients to investigate cellular pathological alterations. We observed that MS fibroblasts showed a senescent morphology associated with iron/lipofuscin accumulation and altered expression of iron metabolism proteins. In addition, we found increased lipid peroxidation and downregulation of antioxidant enzymes expression levels in MS fibroblasts. When challenged against erastin, a ferroptosis inducer, MS fibroblasts showed decreased viability, suggesting increased sensitivity to ferroptosis. Furthermore, MS fibroblasts presented alterations in the expression levels of autophagy-related proteins. Interestingly, these alterations were associated with mitochondrial dysfunction and inflammasome activation. These findings were validated in 7 additional patient-derived cell lines. Our findings suggest that the underlying stress phenotype of MS fibroblasts may be disease-specific and recapitulate the main cellular pathological alterations found in the disease such as mitochondrial dysfunction, iron accumulation, lipid peroxidation, inflammasome activation, and pro-inflammatory cytokine production. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206198 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, multiple sclerosis, iron accumulation, lipid peroxidation, inflammasome, mitochondrial dysfunction To learn more about Aging (Aging-US), 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 9, 2025 — A new #research paper was #published in Aging (Aging-US) Volume 17, Issue 3, on March 5, 2025, titled “Reproductive aging, preimplantation genetic testing for aneuploidy, and the diameter of blastocysts: does size matter?” In this study, a team led by first author Jakub Wyroba from the Malopolski Institute of Fertility Diagnostics and Treatment and Andrzej Frycz Modrzewski Krakow University, and corresponding author Pawel Kordowitzki from Harvard Medical School, Nicolaus Copernicus University, and Charité, found that the size of an embryo and whether it has started hatching can help predict its genetic health. This insight could help fertility clinics select better embryos during in vitro fertilization (IVF), especially in countries or situations where advanced genetic testing is not available. As more women are choosing to have children later in life, fertility challenges related to age are becoming more common. Older maternal age is linked with a higher risk of chromosomal problems in embryos, which can reduce the success of IVF. To identify healthy embryos, many clinics use a test called preimplantation genetic testing for aneuploidy (PGT-A). However, PGT-A is expensive and not available in all countries. This study explored whether embryo quality could be predicted using physical features alone. During IVF, embryos develop in the lab for several days before being transferred into the uterus. Around day five or six, the embryo reaches a stage called the blastocyst. At this point, it begins to break out of its outer shell, called the zona pellucida. This process is called hatching, and it is an important step before the embryo can attach to the uterus and begin a pregnancy. The researchers examined 1150 embryos from women aged 26 to 45 who underwent IVF. They looked at whether the embryos were already starting to hatch and how big they were. They then compared these features with results from genetic tests. They found that smaller embryos that were already hatching were more likely to be chromosomally normal, also called “euploid.” “Of the 1150 blastocysts that underwent PGT-A analysis in this study, 49% were aneuploid.” For women over 35, 51% of small hatching embryos were euploid, compared to just 38% of larger ones that had not started to hatch. Among younger women under 35, the difference was even greater—73% of small hatching embryos were euploid, compared to 58% of large, unhatched ones. The research team also looked at what happened after the embryos were transferred. When embryos were already known to be euploid, both large and small embryos led to similar pregnancy rates. This means the size and hatching behavior mostly matter when genetic testing is not done. This study offers new guidance for IVF clinics. Choosing a small hatching embryo may improve the chances of success, especially for women of advanced age and in clinics that do not use PGT-A. This finding could help make fertility treatment more accessible and affordable. As fertility science continues to advance, insights like this provide practical tools to improve outcomes and bring new hope to individuals and families trying to conceive through IVF. DOI: https://doi.org/10.18632/aging.206215 Corresponding author: Pawel Kordowitzki- p.kordowitzki@umk.pl Video short - https://www.youtube.com/watch?v=0JJIOqWadE4 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 7, 2025 — A new #research paper was #published in Aging (Aging-US) on March 18, 2025, in Volume 17, Issue 3, titled “Mitochondrial oxidative stress or decreased autophagy in osteoblast lineage cells is not sufficient to mimic the deleterious effects of aging on bone mechanoresponsiveness.” Researchers from the University of Arkansas for Medical Sciences, led by first author Ana Resende-Coelho and corresponding authors Melda Onal and Maria Almeida, investigated why bones become less responsive to exercise as people age. They studied two well-known aging-related cellular changes: oxidative stress (a buildup of harmful molecules inside cells) and reduced autophagy (a slowdown in the cell's ability to clean out and recycle damaged parts) to determine whether these could explain the decline in bone strength. Their findings revealed that these changes alone are not enough to account for the reduced bone-building response seen with aging. Physical activity is known to strengthen bones by creating mechanical stress, which activates bone cells like osteocytes to promote new bone formation. However, this process becomes less effective with age, increasing the risk of bone loss and fractures in older adults. The study aimed to uncover why this response weakens over time by focusing on specific age-related changes inside bone-forming cells. “The bone response to loading is less effective with aging, but the cellular and molecular mechanisms responsible for the impaired mechanoresponsiveness remain unclear.” The research team used a well-established mouse model in which pressure was applied to the tibia, simulating the effects of exercise. As expected, bones from older mice showed a weaker response compared to those of younger mice. However, when the researchers examined younger mice genetically modified to have either high oxidative stress or impaired autophagy, as seen in aging, their bones still responded normally to mechanical loading. The researchers also found that damage to the bone's osteocyte network, a system of cells that helps sense and respond to mechanical forces, did not prevent a healthy bone-building response in mice with autophagy deficiencies. This challenges the long-standing idea that deterioration of this cell network is a main cause of age-related bone decline. These results are significant because they eliminate two widely suspected causes of the aging skeleton's reduced responsiveness to exercise. While oxidative stress and autophagy dysfunction are common in older bone, they are not solely responsible for its reduced ability to grow stronger under physical stress. The authors suggest that future studies should explore other possible factors, such as changes in energy metabolism or how bone cells communicate. Overall, this study shows that bone aging is more complex than previously thought. Protecting bone health in older adults may require new strategies that go beyond targeting oxidative stress or autophagy. DOI - https://doi.org/10.18632/aging.206213 Corresponding authors - Melda Onal - MOnal@uams.edu, and Maria Almeida - schullermaria@uams.edu Video short - https://www.youtube.com/watch?v=fHQhA6rOaDc Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206213 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Atg7, tibia compressive loading, Sod2, Osx1-Cre, osteocytes 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 3, 2025 — Aging (Aging-US) is pleased to announce a special Call for Papers for a commemorative collection honoring the legacy of Dr. Mikhail (Misha) Blagosklonny, the founding editor of the journal and a pioneer in aging biology. His groundbreaking work shaped fundamental concepts in the field, particularly regarding the role of mTOR in aging and cancer, the use of rapamycin, bypassing senescence during the process of transformation, personalized medicine, and theories on why we age. This special collection will explore key themes central to Dr. Blagosklonny's scientific contributions, with a focus on mechanistic insights, translational approaches, and theoretical perspectives. We invite original research, reviews, and perspective articles covering topics such as: The role of mTOR in aging and age-related diseases Rapamycin and other pharmacological strategies to extend lifespan Senescence bypass and its implications for cancer and regenerative medicine Personalized medicine approaches in aging and longevity research Theoretical models and evolutionary perspectives on aging The special issue will be guest-edited by leading scientist in the field, David Gems, who will oversee the selection of high-quality contributions that reflect the depth and impact of Dr. Blagosklonny's work. We encourage researchers working on these topics to submit their manuscripts and contribute to this tribute to one of the most influential figures in aging research. SUBMISSION DETAILS: Submission Deadline: December 1, 2025 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 We look forward to your contributions to this special issue and to honoring Dr. Blagosklonny's enduring impact on the field of aging research. To learn more about Aging (Aging-US), 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Could a class of drugs that clear aging cells also help treat Alzheimer's disease? A recent study, featured as the cover for Aging (Volume 17, Issue 3), titled “Differential senolytic inhibition of normal versus Aβ-associated cholinesterases: implications in aging and Alzheimer's disease,” suggests they might—and with remarkable precision. Understanding Alzheimer's Disease Alzheimer's disease is a progressive neurological disorder that gradually steals memory, independence, and a person's sense of identity. A defining feature of Alzheimer's is the buildup of amyloid-β (Aβ) plaques—sticky protein clumps that interfere with communication between brain cells. This disruption is closely linked to changes in a group of enzymes called cholinesterases, especially acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). These enzymes normally play a vital role in regulating neurotransmitters critical for memory, learning, and cognitive function. In Alzheimer's, however, their behavior changes significantly, particularly when they interact with Aβ plaques. The Study: Exploring Senolytics for Alzheimer's Enzyme Inhibition A research team from Dalhousie University in Canada looked into whether senolytic compounds—a class of drugs that eliminate damaged, aging cells often referred to as “zombie” cells—could also target the harmful forms of cholinesterase enzymes found in Alzheimer's disease. Their goal was to see if these compounds could selectively inhibit the disease-associated versions of AChE and BChE, without affecting the healthy forms that are essential for normal brain function. Full blog - https://aging-us.org/2025/04/senolytic-compounds-show-promise-in-targeted-alzheimers-treatments/ DOI - https://doi.org/10.18632/aging.206227 Corresponding author - Sultan Darvesh - sultan.darvesh@dal.ca Video short - https://www.youtube.com/watch?v=CJQFpG9Jn6Y Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206227 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, β-amyloid, acetylcholinesterase, butyrylcholinesterase, cholinesterase inhibitors About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — April 1, 2025 — A new #research paper was #published in Aging (Aging-US) on March 29, 2025, as the #cover of Volume 17, Issue 3, titled “Differential senolytic inhibition of normal versus Aβ-associated cholinesterases: implications in aging and Alzheimer's disease.” In this study, a research team from Dalhousie University, led by Sultan Darvesh, discovered that certain anti-aging compounds, known as senolytics, can block harmful brain enzymes linked to Alzheimer's disease (AD) without affecting healthy ones. Senolytics are compounds that help clear out damaged or “zombie” cells that build up with age and contribute to inflammation and tissue dysfunction. This work provides new insight into how AD-related damage can be precisely targeted, leading the way for safer treatments that protect memory and brain health in older adults. Alzheimer's disease is one of the most common causes of memory loss and dementia. A hallmark of the disease is the buildup of sticky protein clumps in the brain, known as amyloid-beta plaques. Two enzymes—acetylcholinesterase (AChE) and butyrylcholinesterase (BChE)—are found near these plaques. While these enzymes play important roles in brain function, they can also contribute to AD progression when they attach to plaques. Drugs that target these enzymes are already used to help with memory, but they often block both harmful and healthy forms, which can cause unwanted side effects. To investigate a better solution, researchers tested six compounds that are known for their anti-aging or brain-boosting properties. They wanted to know if these compounds could block only the harmful AChE and BChE enzymes forms linked to Alzheimer's disease. Using brain tissue samples from AD patients and enzyme activity assays, they discovered that compounds such as dasatinib and nintedanib, both senolytics, were able to block the forms of AChE and BChE associated with amyloid-beta plaques. These compounds did not affect normal brain enzymes, though. “We show that the selected senolytics and nootropic inhibit ChEs associated with plaques but not the enzymes associated with normal neural elements.” The study also used computer modeling to explore how these compounds interact with the enzymes. The models showed that the enzymes change shape when near plaques, making them easier for certain compounds to target. This change may explain how the drugs can selectively affect only the diseased areas of the brain. While not all compounds worked equally well, the findings offer a new strategy for treating AD. By focusing on the differences between healthy and diseased enzyme forms, researchers may be able to design more precise and effective therapies. This selective approach could improve memory, reduce inflammation, and avoid the side effects of AD's current treatments. In summary, this research opens new possibilities for treating Alzheimer's disease in a more targeted way. It also highlights how discoveries in aging and brain health can work together to create better therapies for neurodegenerative diseases. DOI - https://doi.org/10.18632/aging.206227 Corresponding author - Sultan Darvesh - sultan.darvesh@dal.ca Video short - https://www.youtube.com/watch?v=CJQFpG9Jn6Y Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206227 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 26, 2025 — A new #research paper was #published in Aging (Aging-US) on January 29, 2025, in Volume 17, Issue 2, titled “Diet, lifestyle and telomere length: using Copula Graphical Models on NHANES data.” Researchers Angelo M. Tedaldi, Pariya Behrouzi, and Pol Grootswagers from Wageningen University and Research used data from the National Health and Nutrition Examination Survey (NHANES) to explore how diet and lifestyle affect telomere length, a key marker of cellular aging. They found that inflammation—rather than diet, exercise, or smoking—had the strongest and most consistent association to telomere shortening. The findings suggest that reducing inflammation may be more effective than dietary changes in slowing down the aging process at the cellular level. Telomeres are protective caps at the ends of chromosomes that get shorter as we age. When they become too short, cells lose the ability to divide properly, which can contribute to aging and age-related diseases. Previous studies suggested that healthy habits might protect telomeres, but many focused on a small number of factors and did not account for important elements like inflammation or differences in blood cell composition. This study aimed to take a more complete, data-driven approach. The research team analyzed health data from over 7,000 U.S. adults collected between 1999 and 2002. Using a method called Copula Graphical Modeling, they examined more than 100 variables—such as diet, physical activity, smoking, and blood biomarkers—across three age groups: Young (20–39 years), Middle (40–59 years), and Old (60–84 years). They found that telomere length was most strongly associated to age, levels of C-reactive protein (CRP)—a common marker of inflammation—and gamma-tocopherol, a form of vitamin E found in the blood. Higher CRP levels were consistently associated with shorter telomeres, especially in younger and middle-aged adults. The results suggest that while lifestyle factors like diet and exercise still play a role, their impact on aging may be indirect—mainly through their influence on inflammation. This finding shifts the focus toward managing chronic inflammation as a potentially more effective way to preserve telomere length and promote healthy aging. “The central role played by CRP and the marginal role of antioxidants suggests that telomeres are particularly vulnerable not to oxidative stress, but to inflammation; and they should be protected against it.” The study challenges earlier research that looked at individual lifestyle factors isolated. By using a more advanced and inclusive method, this analysis offers a clearer picture of how health behaviors, biological markers, and aging are connected. Although this research cannot prove a cause-and-effect relationship, it strongly supports the idea that inflammation plays a key role in cellular aging. The authors recommend further long-term studies to better understand how inflammation affects telomere length over time. In the meantime, reducing chronic inflammation may be one of the most important steps to help support healthy aging and reduce the risk of age-related diseases. DOI - https://doi.org/10.18632/aging.206194 Corresponding author - Angelo M. Tedaldi - angelomt1999@gmail.com Video short - https://www.youtube.com/watch?v=C2yXfF7iY6c Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 25, 2025 — A new #research paper was #published in Aging (Aging-US) on January 31, 2025, in Volume 17, Issue 2, titled “Cysteinyl leukotriene receptor 1 modulates retinal immune cells, vascularity and proteolytic activity in aged mice.” The study, led by first author and corresponding author Andreas Koller from the University Hospital of the Paracelsus Medical University, found that blocking an inflammatory receptor called CysLTR1 in the retinas of aging mice improved retinal health. These findings suggest a new approach to slowing age-related vision loss and protecting eye health in older adults. Age-related vision problems are a growing concern worldwide, and inflammation plays a key role in damaging the retina over time. The retina is the part of the eye that captures light and sends visual signals to the brain, making it vital for clear eyesight. In this study, scientists focused on the CysLTR1 receptor, which is known to promote inflammation and is found in high amounts in the retina. They explored whether blocking this receptor could reduce the harmful effects of aging in the eye. To achieve this, researchers treated aged mice with montelukast (MTK), a drug commonly used for asthma, which specifically blocks CysLTR1. The oral treatment lasted eight weeks and results were compared with both untreated aged mice and healthy young mice. After treatment, the older mice showed major improvements in retinal health. One key finding was a reduction in immune cells called microglia, which tend to increase with age and contribute to chronic inflammation in the retina. With CysLTR1 blocked, the number of these immune cells dropped significantly, suggesting reduced retinal inflammation. Lower inflammation is linked to a lower risk of age-related eye diseases like macular degeneration. “The reduction in immune cells caused by Cysltr1 suppression may dampen neuroinflammation, a known promoter of tissue aging.” Another important result was the restoration of blood vessel function. The tiny blood vessels in the retina had narrowed in aging mice, reducing blood flow and oxygen supply to the eye. MTK treatment increased the diameter of these vessels, improving circulation and possibly helping the retina work more efficiently. The study also indicated that blocking CysLTR1 helped boost the retina's natural ability to clear out waste proteins. As we age, this cleaning process slows down, allowing harmful material to build up in the eye. After treatment, the aged mice had stronger proteasome activity—the system responsible for breaking down cellular waste—and fewer signs of waste accumulation. Importantly, the treatment did not harm retinal nerve cells, which are essential for vision. This evidence indicates that the therapy was not only effective but also safe. While more research is needed to confirm these results in humans, this study highlights the potential of repurposing MTK to protect against age-related vision decline. Because it is already an approved drug, testing it for age-related eye diseases like macular degeneration or diabetic retinopathy could move forward more quickly. Blocking inflammation and supporting the eye's natural cleaning systems may be a promising new way to preserve healthy vision in aging populations. DOI - https://doi.org/10.18632/aging.206193 Corresponding author - Andreas Koller - a.koller@salk.at Video short - https://www.youtube.com/watch?v=ngnrPJzHlpI 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

In this installment of the Longevity & Aging Series, Dr. Julia Sidorova from the Department of Laboratory Medicine and Pathology at the University of Washington (Seattle, WA) joined host Dr. Evgeniy Galimov to discuss her co-authored research paper from Volume 16, Issue 20 of Aging (Aging-US), titled “Werner syndrome RECQ helicase participates in and directs maintenance of the protein complexes of constitutive heterochromatin in proliferating human cells.” DOI - https://doi.org/10.18632/aging.206132 Corresponding Author - Julia M. Sidorova - julias@uw.edu Video interview - https://www.youtube.com/watch?v=3yn8O-JA6GE Abstract Werner syndrome of premature aging is caused by mutations in the WRN RECQ helicase/exonuclease, which functions in DNA replication, repair, transcription, and telomere maintenance. How the loss of WRN accelerates aging is not understood in full. Here we show that WRN is necessary for optimal constitutive heterochromatin levels in proliferating human fibroblasts. Locally, WRN deficiency derepresses SATII pericentromeric satellite repeats but does not reduce replication fork progression on SATII repeats. Globally, WRN loss reduces a subset of protein-protein interactions responsible for the organization of constitutive heterochromatin in the nucleus, namely, the interactions involving Lamin B1 and Lamin B receptor, LBR. Both the mRNA level and subcellular distribution of LBR are affected by WRN deficiency, and unlike the former, the latter phenotype does not require WRN catalytic activities. The phenotypes of heterochromatin disruption seen in WRN-deficient proliferating fibroblasts are also observed in WRN-proficient fibroblasts undergoing replicative or oncogene-induced senescence. WRN interacts with histone deacetylase 2, HDAC2; WRN/HDAC2 association is mediated by heterochromatin protein alpha, HP1α, and WRN complexes with HP1α and HDAC2 are downregulated in senescing cells. The data suggest that the effect of WRN loss on heterochromatin is separable from senescence program, but mimics at least some of the heterochromatin changes associated with it. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206132 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Werner progeria, heterochromatin, senescence, nuclear lamina, satellite repeats About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Could the air we breathe, the food we eat, or the chemicals in our everyday environment be accelerating our aging process? A recent study published in Aging suggests that exposure to certain environmental chemicals may be linked to faster biological aging through changes in DNA. These findings could have major implications for public health and longevity. Understanding How Scientists Measure Aging at the DNA Level Aging is not just about wrinkles and gray hair—it happens at the molecular level too. Scientists use epigenetic clocks to measure biological aging, which can differ from a person's actual chronological age. These clocks track DNA methylation, a type of chemical modification that can change over time due to environmental factors like diet, pollution, and chemical exposure. Until now, there has been little research into how widespread environmental chemicals impact these aging markers. The Study: Investigating the Impact of Environmental Pollutants on Aging A research team led by first author Dennis Khodasevich and corresponding author Andres Cardenas from Stanford University, conducted an exposome-wide association study to examine how different environmental pollutants affect epigenetic aging. Using data from the National Health and Nutrition Examination Survey (NHANES), they analyzed blood and urine samples from 2,346 adults aged 50 to 84. The study measured 64 environmental chemicals, including heavy metals, pesticides, plastics, and tobacco-related compounds, to identify potential links to accelerated aging. The study titled “Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey,” was published in Aging on February 11, 2025. Full blog - https://aging-us.org/2025/03/how-environmental-chemicals-may-accelerate-biological-aging/ Paper DOI - https://doi.org/10.18632/aging.206201 Corresponding author - Andres Cardenas - andresca@stanford.edu Video short - https://www.youtube.com/watch?v=WcL-K399a7M 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 About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 19, 2025 — A new #research paper was #published in Aging (Aging-US) on February 27, 2025, in Volume 17, Issue 2, titled “Age, sex, and mitochondrial-haplotype influence gut microbiome composition and metabolites in a genetically diverse rat model.” The research team, led by first author Hoang Van M. Nguyen and corresponding author Archana Unnikrishnan from the University of Oklahoma Health Sciences, studied how aging affects gut bacteria in a special group of rats generated to have genetic diversity similar to humans. Their research found that both biological sex and mitochondrial DNA—the small set of genes inherited only from mothers—play a key role in how gut bacteria change over time. The gut microbiome, a collection of bacteria in the intestines, affects digestion, metabolism, and even brain function. As people age, these bacteria shift, and some of these changes are linked to diseases like Alzheimer's, Parkinson's, and metabolic disorders. However, most studies have looked at either men or women without comparing differences between sexes, and few have explored how mitochondrial DNA might influence these changes. To better understand these factors, researchers analyzed fecal samples from the genetically diverse rats to assess gut bacteria composition and metabolic byproducts. The results showed that aging affects gut bacteria differently in males and females. More bacterial species changed with age in female rats than in males, and only a few changes were consistent across both sexes. These findings suggest that men and women may experience aging differently at the microbial level, which could impact nutrition and disease risk. “Five microbial species changed significantly with age in male rats compared to nine microbial species in female rats. Only three of these microbes changed with age in both male and female rats.” Another key discovery was that mitochondrial DNA influences how gut bacteria evolve with age. These effects were different in males and females, suggesting a deeper connection between mitochondrial function and gut health, with potential implications for personalized medicine and aging research. In addition to studying bacteria, the researchers analyzed metabolic compounds such as short-chain fatty acids and bile acids, which help with digestion. They found that aging altered these compounds based on both sex and mitochondrial DNA. For example, older female rats had higher levels of short-chain fatty acids in their feces, possibly due to differences in nutrient absorption. This study highlights new factors that shape the gut microbiome in aging populations. Understanding how biological sex and mitochondrial DNA influence these changes could lead to targeted approaches for maintaining gut health and preventing age-related diseases. These findings reinforce the importance of personalized health strategies that consider both genetic and biological differences. DOI - https://doi.org/10.18632/aging.206211 Corresponding author - Archana Unnikrishnan - archana-unnikrishnan@ouhsc.edu Video short - https://www.youtube.com/watch?v=RtsqRi2_uAI Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 18, 2025 — A new #research paper was #published by Aging (Aging-US) on March 7, 2025, titled “Accelerated aging associated with cancer characteristics and treatments among breast cancer survivors.” Led by first author Cong Wang and corresponding author Xiao-Ou Shu from Vanderbilt University, this study examines how breast cancer and its treatments contribute to accelerated aging in survivors. Their study revealed that breast cancer patients show signs of faster biological aging compared to cancer-free individuals, with long-term effects lasting up to ten years post-diagnosis. This finding raises concerns about the potential lasting impact of cancer therapies on aging and overall health. Breast cancer is one of the most common cancers in women worldwide, with improved treatments leading to longer survival rates. However, emerging evidence suggests that these treatments may also accelerate aging. The study used Phenotypic Age Acceleration (PAA), a biological marker that estimates a person's aging rate based on blood tests. Researchers compared data from 1,264 breast cancer patients and 429 cancer-free controls. The results indicated that breast cancer survivors had significantly higher PAA at diagnosis and continued to show signs of accelerated aging up to ten years later. “This is the first large study with 10 years of follow-up to evaluate PAA among BC survivors.” The study found that tumor severity played a role in aging acceleration. Women with advanced-stage (Stage III/IV) or high-grade tumors showed the highest levels of aging acceleration. Additionally, treatments such as chemotherapy and endocrine therapy were linked to increased biological aging. One year after diagnosis, chemotherapy was associated with the most significant rise in PAA, while endocrine therapy had long-term effects, increasing aging markers even ten years after treatment. Interestingly, not all cancer treatments had the same effect. Surgery and radiation therapy were associated with lower aging acceleration over time. These findings suggest that systemic therapies, which affect the whole body, may contribute more to aging-related changes than localized treatments. The findings highlight the need for ongoing monitoring of breast cancer survivors beyond their initial recovery. Understanding how cancer treatments influence aging can help improve post-treatment care and potentially lead to strategies that reduce these effects. Further research is needed to explore whether lifestyle changes, medications, or other interventions could slow down aging in cancer survivors. As the number of breast cancer survivors continues to grow, addressing the long-term health consequences of cancer treatment is crucial. This study provides valuable insights into how different factors contribute to accelerated aging, helping to shape future research and healthcare approaches for breast cancer survivors. DOI - https://doi.org/10.18632/aging.206218 Corresponding author - Xiao-Ou Shu - xiao-ou.shu@vumc.org Video short - https://www.youtube.com/watch?v=cfuyzVyDeHY Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 17, 2025 — Impact Journals (Aging's publisher) is pleased to announce its participation as an exhibitor at theAmerican Association for Cancer Research (AACR) Annual Meeting 2025. The meeting is scheduled for April 25-30, 2025, at the McCormick Place Convention Center in Chicago, Illinois. This 2025 AACR Annual Meeting theme, “Unifying Cancer Science and Medicine: A Continuum of Innovation for Impact,” highlights significant advancements and groundbreaking discoveries in cancer research. Aging closely aligns with this mission, dedicated to disseminating impactful scientific research at the intersection of oncology and gerontology. Visit Booth 2815 to meet directly with members of the Aging team, explore the latest research publications, and discuss opportunities for collaboration and manuscript submissions. Aging, supported by its publisher Impact Journals, remains dedicated to promoting innovation, collaboration, and advancing scientific knowledge in aging-related cancer research. About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 12, 2025 — A new #research paper was #published in Aging (Aging-US) on February 25, 2025, Volume 17, Issue 2, titled “Epidemiology and genetic determination of measures of peripheral vascular health in the Long Life Family Study.” Researchers from multiple institutions, led by first author and corresponding author Deidra R. Fricke from the University of Pittsburgh, studied the genetic and lifestyle factors that influence peripheral artery disease (PAD), a condition that restricts blood flow to the legs. Their findings suggest that people from families with exceptional longevity have a lower risk of PAD, possibly due to inherited genetic traits or healthier lifestyle habits. Peripheral artery disease is a common but often undiagnosed condition that affects millions worldwide. It increases the risk of heart disease, stroke, and mobility issues. This study conducted using data from the Long Life Family Study (LLFS), found that individuals from long-lived families have significantly better vascular health than the general population. “Peripheral artery disease (PAD) is a major contributor to morbidity in older adults.” The researchers analyzed over 3,000 participants, including 1,090 long-lived individuals, their 1,554 children, and 362 spouses. Among the oldest participants (average age 89), about 18% had PAD. However, among their children (average age 60), only 1% had PAD—far lower than the expected 12% found in other studies. This finding suggests that certain protective factors, whether genetic or lifestyle-related, help maintain healthier arteries in these families. In the study, key risk factors for PAD were identified, including aging, high blood pressure, smoking, and hypertension medication use. Interestingly, unlike in other studies, high cholesterol and diabetes were not major risk factors in this group. This data further supports the idea that long-lived families may have genetic protective factors that contribute to better vascular health. In addition to lifestyle factors, the study found four genomic regions linked to PAD risk. Three of these were new discoveries, while the fourth was similar but not identical to previously published findings. These genetic markers may help scientists better understand why some individuals are more likely to develop PAD and how to prevent it. “We identified four genomic sites that may harbor variants associated with protection from PAD.” This research highlights the value of studying long-lived families to unlock the secrets of healthy aging and vascular health. Understanding what helps them maintain better artery function could lead to new strategies for preventing PAD, heart disease, and other age-related conditions. Paper DOI: https://doi.org/10.18632/aging.206204 Corresponding author: Deidra R. Fricke — der94@pitt.edu Keywords: aging, ankle-brachial index, peripheral arterial disease, heritability, genomewide linkage analysis, genomewide association study Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 10, 2025 — A new #research paper was #published in Aging (Aging-US) on February 18, 2025, Volume 17, Issue 2, titled “Transcriptomic landscape of cumulus cells from patients

Radiation therapy or radiotherapy, is a common treatment for cancer, but its effectiveness differs across patients. A recent study published as the cover for Volume 17, Issue 2 of Aging explored why this happens. The findings provide valuable insights, particularly for brain cancers like glioblastoma (GBM) and low-grade gliomas (LGG). Understanding Glioblastoma and Low-Grade Gliomas Glioblastoma and LGG are both brain tumors, but they behave in very different ways. GBM is highly aggressive, with most patients surviving only 12 to 18 months, even with surgery, chemotherapy, and radiation therapy. LGG, on the other hand, grows more slowly, and many patients live for decades with proper care. Despite their differences, LGG and GBM are biologically linked. Some LGG tumors eventually transform into GBM, making early treatment decisions critical. Given radiation therapy's effectiveness in GBM, it has often been assumed that LGG patients would also benefit from it. However, a new study titled “Variability in radiotherapy outcomes across cancer types: a comparative study of glioblastoma multiforme and low-grade gliomas” challenges this assumption. Full blog - https://aging-us.org/2025/03/how-radiation-therapy-affects-tumors-glioblastoma-vs-low-grade-gliomas/ Paper DOI - https://doi.org/10.18632/aging.206212 Corresponding author - Morten Scheibye-Knudsen - mscheibye@sund.ku.dk Video short - https://www.youtube.com/watch?v=j91rzDJHXTE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206212 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cancer, biomarkers, radiotherapy, GBM, LGG, survival About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 3, 2025 — A new #research paper was #published in Aging (Aging-US) on February 27, 2025, as the #cover of Volume 17, Issue 2, titled “Variability in radiotherapy outcomes across cancer types: a comparative study of glioblastoma multiforme and low-grade gliomas.” An international research team, led by first author Alexander Veviorskiy from Insilico Medicine AI Limited, Abu Dhabi, UAE, and corresponding author Morten Scheibye-Knudsen from the Center for Healthy Aging, University of Copenhagen, investigated how radiotherapy affects survival in different types of cancer, with a special focus on glioblastoma multiforme (GBM) and low-grade gliomas (LGG). Their findings reveal that radiotherapy has opposite effects in GBM and LGG patients. The study highlights key biological differences between these brain cancer types, emphasizing the need for personalized treatment strategies. Radiotherapy is a standard treatment for many tumors, but its effectiveness varies widely depending on the type of cancer. The researchers began by analyzing data from 32 cancer types using information from The Cancer Genome Atlas (TCGA). They then focused on glioblastoma multiforme (GBM) and low-grade gliomas (LGG), two types of brain cancer with distinct biological behaviors. GBM is an aggressive cancer with poor survival rates, whereas LGG progresses more slowly and often has a better prognosis. “GBM and LGG are particularly interesting to study together because GBM often originates from a preexisting LGG, representing a progression from a lower-grade to a higher-grade malignancy.” The results revealed a striking contrast: patients with GBM who received radiotherapy lived longer, whereas those with LGG had shorter survival times after treatment. To understand the reasons behind this, the researchers analyzed gene expression and signaling pathways. They identify several biological processes that may influence radiotherapy outcomes. For example, GBM tumors have weaker DNA repair mechanisms, making them more vulnerable to radiation-induced damage, which allows radiotherapy to effectively kill cancer cells. In contrast, LGG tumors have stronger DNA repair systems, helping cells survive radiation better and potentially reducing the treatment's effectiveness. Additionally, differences in immune system activity and genetic mutations—such as EGFR alterations—were linked to worse survival in LGG patients who received radiotherapy. These findings highlight the need for a more personalized approach to treating brain cancer. The study proposes that a universal approach to radiotherapy is not appropriate, particularly for patients with LGG. Instead, personalized treatment strategies based on genetic and molecular characteristics could improve patient survival outcomes. The research also raises the possibility of combining radiotherapy with targeted therapies, such as immune-boosting therapies or DNA repair inhibitors, to enhance its effectiveness. In conclusion, this study highlights the complexity of brain cancer treatment and the need for further research to refine therapeutic strategies. By understanding the molecular and genetic differences between the different types of cancers, more effective and personalized approaches can be developed to improve survival and quality of life for brain cancer patients. DOI - https://doi.org/10.18632/aging.206212 Corresponding author - Morten Scheibye-Knudsen - mscheibye@sund.ku.dk Video short - https://www.youtube.com/watch?v=j91rzDJHXTE 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 5, 2025 — A new #research paper was #published in Aging (Aging-US) on February 11, 2025, Volume 17, Issue 2, titled “Exposome-wide association study of environmental chemical exposures and epigenetic aging in the national health and nutrition examination survey.” First author Dennis Khodasevich and corresponding author Andres Cardenas from Stanford University, and colleagues from other U.S. institutions, studied how exposure to harmful chemicals in the environment affects aging. Using data from the National Health and Nutrition Examination Survey (NHANES), they discovered that cadmium, lead, and cotinine are linked to faster biological aging, a process that can increase the risk of age-related diseases. The study analyzed data from 2,346 U.S. adults aged 50 to 84 who participated in a national health survey. Researchers tested their blood and urine for 64 different chemicals, including metals, pesticides, and industrial pollutants. They assessed how these exposures influenced eight different epigenetic aging markers—biological clocks that measure how fast a person's body is aging at the DNA level. "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." The strongest effects were linked to cadmium, a toxic metal found in cigarette smoke and some foods. People with higher levels of cadmium in their blood showed signs of accelerated aging. Higher levels of cotinine, a chemical related to tobacco exposure, were also linked to increased biological age, reinforcing the harmful effects of smoking. Additionally, lead exposure, a heavy metal found in old paint and contaminated water, was also associated with faster aging. The researchers also found that some pollutants, including a type of PCB (PCB118) and a type of dioxin (HpCDD), were linked to slower biological aging. However, it is unclear if this fact is beneficial, as past research shows that slower aging in some cases can still be linked to health risks. This study is one of the largest to investigate how pollution affects the aging process. Unlike previous research that focused on only a few chemicals, it examined a wide range of pollutants in a diverse group of people. The findings suggest that everyday exposure to toxic substances can speed up aging at the cellular level, increasing the risk of age-related diseases. In summary, these findings raise concerns about how widespread environmental contaminants may accelerate aging and contribute to chronic diseases such as heart disease, cancer, and cognitive decline. Reducing exposure to toxic substances like cadmium and lead—found in cigarettes, polluted air, and contaminated food—could help slow biological aging and improve long-term health. These insights highlight the need for stronger environmental health policies to protect individuals from premature aging and disease. DOI - https://doi.org/10.18632/aging.206201 Corresponding author - Andres Cardenas - andresca@stanford.edu Video short - https://www.youtube.com/watch?v=WcL-K399a7M Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — February 24, 2025 — A new #researchpaper was #published in Aging (Aging-US) on January 22, 2025, in Volume 17, Issue 1, titled “EpiAge: a next-generation sequencing-based ELOVL2 epigenetic clock for biological age assessment in saliva and blood across health and disease.” The research team, experts from both industry (EpiMedTech Global, HKG Epitherapeutics Ltd) and academic institutions (McGill University, Oxford University, University of Catania, and the Research Institute-IRCCS), led by first author David Cheishvili and corresponding author Moshe Szyf, have developed EpiAgePublic, a new method to estimate biological age using only three key DNA sites in the ELOVL2 gene, a well-known marker of aging. Unlike traditional methods that require analyzing thousands of DNA regions, this approach simplifies the process while maintaining accuracy. Their findings show that EpiAgePublic performs as well as, or even better than, more complex models in predicting biological age in diverse populations. Biological age measures how fast or slow a person's body is aging. It can be different from chronological age and is influenced by genetics, lifestyle, and health conditions. Understanding biological aging can help researchers and clinicians identify age-related diseases like Alzheimer's disease and develop anti-aging treatments. However, many existing biological age tests rely on expensive and complicated processes. The EpiAgePublic model overcomes these challenges with a simple yet powerful approach. The study analyzed data from over 4,600 individuals across different health conditions, including Alzheimer's disease and HIV. It confirmed that EpiAgePublic accurately tracks aging patterns and can identify factors such as chronic illness or stress that accelerate the aging process. Importantly, the researchers demonstrated that the test works well using saliva samples, offering a convenient and non-invasive alternative to blood-based tests. This makes it easier to conduct epigenetic age testing in both clinical and research settings. “The simplicity and precision of epiAgePublic, designed for compatibility with next-generation sequencing (NGS) technologies, mark a significant step forward in the field of epigenetic research.” The ability to measure epigenetic aging with a quick and cost-effective test has significant implications for healthcare, longevity research, and personalized medicine. This method could be used in hospitals, wellness clinics, and longevity studies to track aging and evaluate the effectiveness of anti-aging interventions. It may also help clinicians detect early signs of aging-related diseases, allowing for better preventive care. Finally, the study's findings highlight the advantages of next-generation sequencing in epigenetic research, leading the way for more precise and accessible aging diagnostics. Future research will explore how this model can be expanded to other health conditions and used in routine medical practice. DOI - https://doi.org/10.18632/aging.206188 Corresponding author - Moshe Szyf - moshe.szyf@epimedtech.com Author interview - https://www.youtube.com/watch?v=NA8Vctks0gY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206188 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — February 26, 2025 — A new #research paper was #published in Aging (Aging-US) on January 27, 2025, in Volume 17, Issue 1, titled “Age-invariant genes: multi-tissue identification and characterization of murine reference genes.” Aging is a process driven by changes in gene activity, but researchers from Yale University School of Medicine and Altos Labs, led by first author John T. González and corresponding author Albert T. Higgins-Chen, have identified a set of genes that remain unchanged throughout the aging process. This discovery could improve the accuracy of aging research and provide insights into why some genes stay unchanged while others decline. “Reference genes have mostly been identified and validated in young organisms, and no systematic investigation has been done across the lifespan.” The study looked at gene activity in 17 different tissues in mice, from 1 month old to over 21 months old. Scientists used advanced bioinformatic analysis methods to analyze RNA sequencing data. They found nine genes that stayed the same across all tissues, as well as other genes that remained stable in specific tissues. These genes are usually shorter and have special DNA regions called CpG islands, which may help cells stay healthy and resist aging. Their stability throughout aging was confirmed by analyzing different datasets and using RT-qPCR. One of the most significant findings is that these stable genes are linked to essential cellular functions, such as mitochondrial activity and protein maintenance. This challenges the common belief that all aspects of aging involve gene dysregulation. Instead, the findings suggest that some cellular processes may naturally resist aging, leading the way for new research on longevity and potential anti-aging therapies. “Biological processes that change with age and those that resist age-related dysregulation are two sides of the same coin, and both will need to be investigated to fully understand aging.” Another key finding is that commonly used reference genes, such as GAPDH and ACTB, fluctuate with age, making them unreliable for aging studies. No single classical reference gene was found to be stable across all tissues. Researchers often use these reference genes as a control to measure gene activity, but if their expression changes over time, it can lead to inaccurate results. By identifying new, stable reference genes, this study provides scientists with better tools for studying aging-related diseases, regenerative medicine, and longevity science. Understanding how certain genes remain unchanged throughout life suggests that they may play a protective role in aging and could potentially be used to develop treatments that slow down age-related decline. While further research is needed, this discovery sets a new standard for measuring gene activity in aging studies and could have a significant impact on aging research and medicine. DOI - https://doi.org/10.18632/aging.206192 Corresponding author - Albert T. Higgins-Chen - a.higginschen@yale.edu About Aging-US The mission of the journal is to understand the mechanisms surrounding aging and age-related diseases, including cancer as the main cause of death in the modern aged population. The journal aims to promote 1) treatment of age-related diseases by slowing down aging, 2) validation of anti-aging drugs by treating age-related diseases, and 3) prevention of cancer by inhibiting aging. (Cancer and COVID-19 are age-related diseases.) 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/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM