Aging-US

BUFFALO, NY — March 13, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 2, 2026, titled “D, L-Buthionine-(S, R)-sulfoximine recapitulates the anti-obesity effects of sulfur amino acid restriction without the associated deleterious effects on bone in male mice.” Led by Naidu B. Ommi from the Orentreich Foundation for the Advancement of Science — with corresponding author Sailendra N. Nichenametla from the same institution — the study tests whether the glutathione (GSH)-lowering compound D, L-buthionine-(S, R)-sulfoximine (BSO) reproduces the anti-obesity effects of sulfur amino acid restriction (SAAR) without causing the bone loss seen with SAAR diets. Using diet-induced obese male C57BL6/NTac mice fed high-fat diets, the authors compared: a control methionine-replete diet, a SAAR diet (low methionine, no cysteine), SAAR plus the GSH precursor N-acetylcysteine (NAC), and control diet plus BSO in drinking water. Using body-composition, micro-CT, histomorphometry, and biomechanical testing, the team confirmed prior work that SAAR reduces body fat but also lowers trabecular and cortical bone mineral density, increases marrow adiposity, reduces osteoblast numbers, and weakens bone biomechanical strength. Crucially, while NAC supplementation reversed the bone defects of SAAR (implicating cysteine/glutathione restriction in bone loss), BSO reproduced the lean, anti-obesity phenotype without producing the deleterious bone effects observed in SAAR mice. In short, BSO recapitulated the anti-obesity benefits of SAAR without causing the same bone loss — a finding with potential relevance to developing anti-obesity strategies that avoid skeletal harm. “Despite its anti-obesity effects, BSO did not exert any detrimental effects on bones.” The authors emphasize next steps and caveats. They call for mechanistic studies to define how GSH lowering drives fat loss yet spares bone under BSO treatment, investigations of age-at-onset, tissue-specific, and sex-specific effects, and long-term safety studies to assess off-target or delayed adverse effects of BSO before any clinical development. The paper frames BSO as a promising tool compound to dissect the beneficial versus deleterious axes of sulfur amino acid biology, but not yet as a human therapy without further preclinical evaluation. DOI - https://doi.org/10.18632/aging.206358 Corresponding author - Sailendra N. Nichenametla - snichenametla@orentreich.org Abstract video - https://www.youtube.com/watch?v=0adFA_b-q1Q Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206358 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - bone, aging, methionine, glutathione, redox To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 10, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 3, 2026, titled “P38 MAPK is involved in epigenetic regulation of fibrotic genes in replication induced senescence in lung fibroblasts.” Led by Shan Zhu — with corresponding author Yan Y Sanders from the Department of Biomedical and Translational Sciences, Eastern Virginia Medical School (Macon & Joan Brock Virginia Health Sciences at Old Dominion University) — the study examines how the stress-activated kinase p38 MAPK contributes to persistent profibrotic gene expression in replicative (passage-driven) senescence of human lung fibroblasts and in primary fibroblasts from patients with idiopathic pulmonary fibrosis (IPF). Using IMR90 lung fibroblasts at low and high population-doubling levels and primary IPF fibroblasts, the authors show that TGF-β1 upregulates profibrotic genes (α-SMA and Col3A1) in both young and near-senescent cells, but that high-PDL (near-senescent/senescent) fibroblasts exhibit a delayed but sustained p38 MAPK response to TGF-β1. Pharmacological inhibition of p38 MAPK (SB202190) blunted profibrotic transcription and reduced H4K16 acetylation (H4K16ac) enrichment at α-SMA and Col3A1 promoters, indicating an epigenetic mechanism linking p38 signaling to fibrotic gene activation. “These findings suggest that a p38 MAPK–dependent epigenetic mechanism is involved in fibroblast activation, supporting the therapeutic potential of p38 MAPK inhibition for treating age-related fibrotic diseases such as IPF.” The authors place these molecular results in a clinical context: persistent fibroblast activation and senescence are features of IPF and other age-associated fibrotic disorders, and the data here support targeting p38 MAPK to interrupt an epigenetically reinforced profibrotic program. The study used multiple readouts (western blot, RT-qPCR, ChIP for H4K16ac) and included primary IPF cells to strengthen translational relevance, while also noting that further work is required to test safety and efficacy in vivo. The paper outlines clear next steps: determine the upstream triggers that sustain p38 signaling in near-senescent fibroblasts, map the chromatin-level events downstream of p38 that maintain H4K16ac at profibrotic promoters, and evaluate p38 inhibition in animal models of age-related pulmonary fibrosis. The authors also recommend exploring whether epigenetic modulators that reverse H4K16ac enrichment can synergize with kinase inhibition to restore repair capacity without impairing normal tissue healing. DOI - https://doi.org/10.18632/aging.206357 Corresponding author - Yan Y Sanders - sandery@odu.edu Abstract video - https://www.youtube.com/watch?v=yP0CwWMUhnY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206357 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, senescence, fibroblast activation, p38 MAPK, lung fibrosis, H4K16Ac To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Biomarkers of aging help researchers understand how diseases influence the body over time. However, most current biomarkers rely on measurements from mixed cell populations, making it difficult to distinguish between changes caused by shifts in cell types and aging processes occurring within individual cells. In this study, titled “Single-cell transcriptomics reveal intrinsic and systemic T cell aging in COVID-19 and HIV” and published in Volume 18 of Aging-US, researchers used single-cell RNA sequencing to analyze aging-related changes in human T cells. They developed Tictock, a single-cell transcriptomic clock that predicts both cellular age and T cell type across six human T cell subsets. Applying this tool, the researchers found that acute COVID-19 was associated with increased proportions of CD8⁺ cytotoxic T cells, while T cell composition remained relatively stable in individuals with HIV receiving antiretroviral therapy (HIV+ART). Despite these differences, both conditions showed signs of accelerated transcriptomic aging, particularly in naïve CD8⁺ T cells. Further analysis identified shared aging-related genes and biological pathways linked to ribosomal components and TNF receptor binding. These findings demonstrate how single-cell transcriptomic biomarkers can help separate systemic immune changes from cell-intrinsic aging processes, providing new tools to measure immune aging in disease. DOI - https://doi.org/10.18632/aging.206353 Corresponding author - Eric Verdin - EVerdin@buckinstitute.org Abstract video - https://www.youtube.com/watch?v=_r3AF7OrgKY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206353 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, transcriptomic clock, aging biomarkers, systemic aging, intrinsic aging To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Aging reshapes the immune system in two fundamental ways: it alters the proportions of different immune cell types circulating in the blood, and it induces molecular changes within each individual cell. For years, researchers have struggled to disentangle these two intertwined processes using standard “bulk” measurements, which average signals across millions of cells and obscure what is happening at the single-cell level. A new research paper, titled “Single-cell transcriptomics reveal intrinsic and systemic T cell aging in COVID-19 and HIV” published in Volume 18 of Aging-US by researchers at the Buck Institute for Research on Aging in California, the University of Southern California, and the University of Copenhagen, introduces an innovative solution. The team of Alan Tomusiak, Sierra Lore, Morten Scheibye-Knudsen, and corresponding author Eric Verdin, developed a novel tool called Tictock (T immune cell transcriptomic clock) that uses single-cell RNA sequencing to separately measure systemic and cell-intrinsic components of immune aging, and then applied it to understand how COVID-19 and HIV affect T cells. Full blog - https://aging-us.org/2026/03/tictock-a-single-cell-clock-measures-immune-aging-in-viral-infections/ Paper DOI - https://doi.org/10.18632/aging.206353 Corresponding author - Eric Verdin - EVerdin@buckinstitute.org Abstract video - https://www.youtube.com/watch?v=_r3AF7OrgKY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206353 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, transcriptomic clock, aging biomarkers, systemic aging, intrinsic aging To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — March 3, 2026 — A new #research perspective was #published in Volume 18 of Aging-US on February 24, 2026, titled “A decline in glycolytic ATP production is the fundamental mechanism limiting lifespan; species with an optimal rate of decline over time survived.” Led by Akihiko Taguchi — who is also the corresponding author and is affiliated with the Department of Regenerative Medicine Research, Foundation for Biomedical Research and Innovation at Kobe — the perspective advances a unifying conceptual framework in which a programmed or selected decline in glycolytic ATP production over the lifespan underlies aging phenotypes across species. The authors argue that glycolysis supplies the rapid ATP required for cell division and DNA/mitochondrial repair, and that a progressive reduction in glycolytic ATP with age can explain reduced cell proliferation, impaired repair, and other hallmark features of aging. “The simple explanation is that only species that happened to have an optimal rate of reduction in glycolytic ATP production over time were selected and survived through generational changes.” The perspective synthesizes evidence from comparative biology, cellular metabolism, and translational studies to link glycolytic decline with lifespan variation among species — for example, contrasting short-lived rodents with long-lived species such as the naked mole rat, which maintain high glycolytic flux in low-oxygen niches. The authors also highlight mechanisms connecting glycolysis to mitophagy, telomere dynamics, and proteostasis, arguing that maintaining glycolytic ATP supports repair processes while a shift toward oxidative metabolism improves energy efficiency under resource limitation but reduces rapid-repair capacity. The authors propose several concrete next steps to test the hypothesis. These include in vivo and in vitro interventions that modulate glycolysis (for example, gene transfer of glycolysis-related enzymes or pharmacologic activators such as terazosin), longitudinal measurements of glycolytic ATP production across aging cohorts, and comparative studies across species with differing lifespans to define the “optimal rate” of decline. They also suggest mechanistic studies of gap-junction–mediated metabolic coupling (for example, between hematopoietic stem cells and endothelium) and experiments to determine whether restoring glycolytic flux can rescue age-related deficits in DNA repair and tissue regeneration. While the perspective offers a coherent conceptual model, the authors are explicit about limitations and caution: the idea is currently a hypothesis that requires experimental validation, and the evolutionary rationale (selection for an optimal rate of glycolytic decline) must be tested by comparative and mechanistic work. Translation to human rejuvenation therapies — whether via stem-cell approaches, metabolic activators, or gene transfer — will require careful preclinical studies to evaluate efficacy, safety, and long-term consequences. DOI - https://doi.org/10.18632/aging.206356 Corresponding author - Akihiko Taguchi - taguchi@fbri.org Abstract video - https://www.youtube.com/watch?v=rA23radaoqI Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — February 27, 2026 — A new #research paper was #published in Volume 18 of Aging-US on February 6, 2026, titled “Causal effects of inflammation on long-term mortality: a Mendelian randomization study.” Led by Eliano P. Navarese from Department of Life and Health Sciences, Link Campus University and SIRIO MEDICINE Research Network, Nicolaus Copernicus University, who is also the corresponding author — the study used large-scale Mendelian randomization (MR) to test whether genetically proxied levels of inflammatory biomarkers causally influence long-term all-cause mortality. The analysis combined genome-wide association instruments from more than 750,000 individuals and used FinnGen mortality data (median follow-up 11.7 years) to assess effects on overall survival and major cardiovascular endpoints. Using robust MR methods and multiple sensitivity analyses, the authors report that genetically higher IL6R (soluble IL-6 receptor) levels were associated with reduced all-cause mortality (odds ratio per 1-SD increase: 0.95; 95% CI: 0.91–0.98), and with lower risk of atrial fibrillation, coronary artery disease, stroke, and lung cancer. By contrast, genetically higher IL6 levels were associated with increased mortality (OR 1.05; 95% CI: 1.02–1.08). No significant causal effects were observed for CRP or GDF15, suggesting those markers more likely reflect disease burden than drive it. “These results support IL6R antagonism as a potential strategy for cardiovascular disease prevention.” The authors emphasize that the opposing directions for IL6 and IL6R point to distinct biological mechanisms: IL6 likely promotes chronic pro-inflammatory states that increase cardiovascular risk, while higher circulating IL6R (reflecting altered receptor shedding and signaling) appears to dampen harmful IL6 activity at the vessel wall and myocardium, yielding cardiovascular protection. Sensitivity and cis-MR analyses reinforced the IL6R protective signal and showed minimal evidence of directional pleiotropy. Together, the genetic evidence aligns with clinical trial data for IL6R antagonists in other settings and supports further evaluation of IL6R-targeted strategies for cardiovascular prevention. The paper also notes important limitations and next steps. Analyses were restricted to individuals of European ancestry, so results require replication in other ancestries. Translating genetic evidence into preventive therapies will need careful clinical evaluation, long-term safety assessment, and trials designed for primary prevention in high-risk populations. The authors also call for additional mechanistic work to map how IL6/IL6R modulation alters vascular inflammation and downstream disease processes. DOI - https://doi.org/10.18632/aging.206352 Corresponding author - Eliano P. Navarese - elianonavarese@gmail.com Abstract video - https://www.youtube.com/watch?v=Br1A0jgU-4M Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206352 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, mendelian randomization, inflammatory biomarkers, mortality, cardiovascular disease To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Aging-US sincerely thanks all reviewers who contributed their expertise and time during 2025. Rigorous and constructive peer review is essential to scientific progress. Through their careful evaluations, our reviewers played a central role in maintaining the scientific quality, integrity, and credibility of the journal. Their efforts also directly support one of the core missions of Aging-US, which is to increase the visibility and impact of high-quality research in the biology of aging and age-related disease. We are deeply grateful for this commitment to excellence and to the aging research community, and we look forward to continued collaboration in the coming year. –Marco Demaria Editor-in-Chief, Aging-US ____________ To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — February 24, 2026 — A new #research paper was #published in Volume 18 of Aging-US on February 10, 2026, titled “Aging-associated mitochondrial circular RNAs.” Led by first author Hyejin Mun from the University of Oklahoma — with corresponding authors Je-Hyun Yoon from the University of Oklahoma and Young-Kook Kim from Chonnam National University Medical School — the study profiles mitochondrial circular RNAs in Peripheral Blood Mononuclear Cells (PBMCs) from young and old human cohorts and probes how mitochondrial circRNAs and the mitochondrial RNA-binding protein GRSF1 relate to mitochondrial metabolism and cellular senescence. Using total RNA sequencing of PBMCs from young and old donors and complementary cell-based experiments, the authors report that a large fraction of circular RNA junctions originates from the mitochondrial genome, with MT-RNR2 producing the most abundant circular junctions. They show that circMT-RNR2 levels are depleted in older cohorts and in replicative senescence of human fibroblasts, and that the mitochondria-localized RNA-binding protein GRSF1 interacts with both linear and circular MT-RNR2. Loss of GRSF1 reduced circMT-RNR2 levels, decreased mitochondrial TCA intermediates (fumarate and succinate), and accelerated cellular senescence and mitochondrial dysfunction — findings that link mitochondrial circRNAs to mitochondrial energetics and proliferative status in younger cells. “Taken together, our findings demonstrate the existence and possible function of circular MT-RNR2 during human aging and senescence, implicating its role in promoting the TCA cycle.” The authors note key limitations and outline next steps: clarifying the biogenesis mechanism of mitochondrial circular RNAs (including whether trans-splicing contributes), mapping direct interactions between mitochondrial transcripts and metabolic enzymes, and performing mechanistic studies (in vivo and in additional human cohorts) to test how circMT-RNR2 and GRSF1 influence mitochondrial energetics and organismal aging. These follow-ups will determine whether mitochondrial circular RNAs are actionable targets for modulating mitochondrial metabolism or delaying aspects of cellular aging. DOI - https://doi.org/10.18632/aging.206354 Corresponding authors - Je-Hyun Yoon - jehyun-yoon@ou.edu, and Young-Kook Kim - ykk@jnu.ac.kr Abstract video - https://www.youtube.com/watch?v=f8uZ6_tcOHw Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206354 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, circular RNA, MT-RNR2, GRSF1, TCA cycle To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — February 19, 2026 — A new #research paper was #published in Volume 18 of Aging-US on February 8, 2026, titled “Single-cell transcriptomics reveal intrinsic and systemic T cell aging in COVID-19 and HIV.” In this study, co-first authors Alan Tomusiak from the Buck Institute for Research on Aging and the University of Southern California, and Sierra Lore from the Buck Institute for Research on Aging and the University of Copenhagen, together with corresponding author Eric Verdin from the Buck Institute for Research on Aging, developed a new single-cell transcriptomic clock called T immune cell transcriptomic clock (Tictock) to measure aging in specific immune cells. Immune aging increases susceptibility to infection, cancer, and chronic inflammatory disease. Most aging clocks, used to measure it, rely on bulk measurements from mixed cell populations. As a result, they cannot determine whether age-related signals reflect shifts in cell proportions or true molecular aging within defined immune cells. To address this limitation, the research team used single-cell RNA sequencing, a method that measures gene expression in individual cells. They analyzed nearly two million immune cells from the blood of healthy adults to develop Tictock. This tool integrates automated classification of six canonical T cell subsets with cell-type specific age prediction models. This design enables the separation of systemic aging, reflected by changes in cell proportions, from intrinsic aging, which occurs within individual cells. When the team applied Tictock to patients with acute COVID-19, they found two clear effects. First, COVID-19 altered T cell composition, including significant reductions in naïve CD8 and naïve CD4 T cells. Second, the infection increased the biological age of naïve CD8 T cells. In people living with HIV who were receiving long-term antiretroviral therapy, T cell proportions remained largely stable. However, naïve CD8 T cells still showed signs of accelerated aging. The study also uncovered shared biological pathways linked to immune aging. Many of the genes that predicted age were involved in ribosomes, the structures that help cells produce proteins. The researchers also observed that older immune cells often had shorter average transcript lengths, a feature previously linked to aging. These findings suggest that changes in protein production and gene regulation play an important role in immune decline. “Gene Ontology enrichment of 209 genes shared across six clock models identified common pathways including the cytosolic small ribosomal subunit, TNF receptor binding, and cytosolic ribosome components.” Overall, Tictock was designed to measure relative aging within defined T cell populations rather than overall biological aging. By distinguishing systemic from cell-intrinsic immune aging, it provides a clearer understanding of how viral infections such as COVID-19 and HIV reshape immune function. This approach enables the study of immune aging at single-cell resolution and may support improved immune risk assessment in clinical and research settings. DOI - https://doi.org/10.18632/aging.206353 Corresponding author - Eric Verdin - EVerdin@buckinstitute.org Abstract video - https://www.youtube.com/watch?v=_r3AF7OrgKY Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​. MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — February 18, 2026 — A new #editorial was #published in Volume 18 of Aging-US on February 8, 2026, titled “Polyploidy-induced senescence: Linking development, differentiation, repair, and (possibly) cancer?” In this editorial, Iman M. Al-Naggar of the University of Connecticut School of Medicine, UConn Health, and the University of Connecticut Center on Aging, with George A. Kuchel of the University of Connecticut Center on Aging, examines the biological and clinical significance of polyploidy-induced senescence. The authors discuss how this process may contribute to normal tissue development and long-term repair, while also influencing cancer risk. Their perspective centers on the bladder and outlines how aging-related cellular changes may shape tumor initiation. Aging remains the strongest risk factor for bladder cancer, which is predominantly of urothelial origin. Cellular senescence is defined as a stable growth arrest in which cells remain metabolically active but no longer divide. Polyploidy refers to cells that contain extra copies of their genome. Although polyploidy is frequently associated with cancer, it also occurs in several healthy tissues as part of normal development and adaptation to stress. The editorial highlights increasing evidence that polyploidy and senescence can function together as a coordinated biological program. The authors focus on bladder umbrella cells, which form the barrier between urine and the bloodstream. In mice, these cells naturally become polyploid early in life and display markers of senescence across the lifespan. Rather than representing dysfunction, this state may help maintain tissue architecture, reinforce barrier integrity, and support resistance to environmental stress. In this context, polyploidy-induced senescence may act as a differentiation program that preserves organ structure. “Polyploidization and senescence may be interrelated stress responses, yet they have been studied mostly in isolation.” However, this protective mechanism may become unstable. Polyploidy-induced senescence depends on intact tumor suppressor pathways, including regulators such as p16. If these safeguards are lost through mutation, deletion, or epigenetic silencing, polyploid senescent cells may escape growth arrest. Re-entry into the cell cycle under these conditions may promote chromosomal instability and aneuploidy, increasing the likelihood of malignant transformation. The authors propose that a subset of bladder cancers may arise from polyploid umbrella cells that have bypassed this senescent barrier. The editorial also discusses implications for cancer therapy. Many anticancer treatments induce senescence and polyploidization in tumor cells. Although this approach can initially suppress proliferation, some polyploid cancer cells may later adapt, reduce their ploidy, and resume division, contributing to relapse and treatment resistance. Understanding how polyploidy and senescence interact may therefore inform therapeutic strategies. Overall, the authors emphasize the need to study polyploidy and senescence together rather than in isolation. Integrating ploidy assessment into large-scale mapping efforts of senescent cells may improve insight into aging biology, tumor initiation, and resistance to therapy. DOI: https://doi.org/10.18632/aging.206355 Corresponding author: Iman M. Al-Naggar - alnaggar@uchc.edu Introduction video - https://www.youtube.com/watch?v=3Cl-JoV-j0o https://www.Aging-US.com​​ MEDIA@IMPACTJOURNALS.COM

Aging has long been explained in different ways. One traditional view is that it results from the gradual accumulation of molecular damage over time. Another perspective, based on evolutionary theory, suggests that natural selection strongly protects health during youth and reproductive years but becomes less effective later in life. As a result, biological effects that appear in older age may persist because they have little impact on reproduction. Over the past two decades, researchers have also explored the idea that biological programs beneficial early in life may continue operating later in ways that become harmful. Processes that once supported growth, repair, and reproduction may, with time, contribute to chronic disease. A recent review article, titled “Aging as a multifactorial disorder with two stages,” published in Aging-US by researchers at University College London and Queen Mary University of London, brings these different perspectives together into a unified model, to propose a broader explanation of how aging-related diseases develop. The review appears in a special issue honoring the late scientist Misha Blagosklonny, whose theoretical work on programmatic aging significantly influenced the field. Full blog - https://aging-us.org/2026/02/how-aging-leads-to-chronic-disease-a-two-stage-model/ Paper DOI - https://doi.org/10.18632/aging.206339 Corresponding author - David Gems - david.gems@ucl.ac.uk Abstract video - https://www.youtube.com/watch?v=d4TSI4Ot3yM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206339 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, C. elegans, disease, hyperfunction, multifactorial model To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

While maternal health has traditionally been central to research on pregnancy and child development, there is growing recognition that paternal factors also play a role, particularly the father's age. Several studies have found a modest increase in risk of neurodevelopmental conditions, including autism spectrum disorder, among children born to older fathers. However, the biological mechanisms underlying this association are still not fully understood. One emerging explanation involves epigenetics, chemical modifications that influence how genes are expressed without altering the underlying DNA sequence. Among these is DNA methylation. Earlier studies have suggested that sperm from older men may carry age-related changes in DNA methylation, but few have explored these patterns on a genome-wide scale or focused specifically on regions that are most likely to influence offspring development. The Study: Exploring Age-Dependent Methylation at Imprint Control Regions in Human Sperm In a study, titled “Age-specific DNA methylation alterations in sperm at imprint control regions may contribute to the risk of autism spectrum disorder in offspring,” published in Aging-US and selected as the Editors' Choice for January, 2026, researchers investigated how DNA methylation patterns in sperm change with age. The study was led by first authors Eugenia Casella and Jana Depovere, with corresponding author Adelheid Soubry from the University of Leuven. Full blog - https://aging-us.org/2026/02/epigenetic-changes-in-sperm-may-explain-association-between-paternal-age-and-autism-risk/ Paper DOI - https://doi.org/10.18632/aging.206348 Corresponding author - Adelheid Soubry - adelheid.soubry@kuleuven.be Video abstract - https://www.youtube.com/watch?v=XC3p49Uw49w Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206348 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenome, sperm, 450K, imprinting, autism To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Senior Scientist Fedor Galkin from Insilico Medicine in Abu Dhabi, UAE, joins Dr. Evgeniy Galimov to discuss a research paper he co-authored in Volume 17, Issue 8 of Aging-US, titled “AI-driven toolset for IPF and aging research associates lung fibrosis with accelerated aging.” DOI - https://doi.org/10.18632/aging.206295 Corresponding author - Alex Zhavoronkov - alex@insilico.com Video interview - https://www.youtube.com/watch?v=PV6DyIV7X7U Abstract video - https://www.youtube.com/watch?v=24lX2lHbt7o Longevity & Aging Series - https://www.aging-us.com/longevity Abstract Idiopathic pulmonary fibrosis (IPF) is a condition predominantly affecting the elderly and leading to a decline in lung function. Our study investigates the aging-related mechanisms in IPF using artificial intelligence (AI) approaches. We developed a pathway-aware proteomic aging clock using UK Biobank data and applied it alongside a specialized version of Precious3GPT (ipf-P3GPT) to demonstrate an AI-driven mode of IPF research. The aging clock shows great performance in cross-validation (R2=0.84) and its utility is validated in an independent dataset to show that severe cases of COVID-19 are associated with an increased aging rate. Computational analysis using ipf-P3GPT revealed distinct but overlapping molecular signatures between aging and IPF, suggesting that IPF represents a dysregulation rather than mere acceleration of normal aging processes. Our findings establish novel connections between aging biology and IPF pathogenesis while demonstrating the potential of AI-guided approaches in therapeutic development for age-related diseases. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206295 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, IPF, generative AI, transformer, proteomics To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ YouTube - https://www.youtube.com/@Aging-US Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

When we think of aging, we often picture wrinkles or gray hair. But aging also occurs deep within our cells. One key area of research focuses on “epigenetic aging,” the gradual changes in how DNA is regulated over time. These changes are tracked using tools called epigenetic clocks, which estimate a person's biological age based on specific molecular markers in the blood. Unlike chronological age, biological age reflects the body's functional state and can be influenced by health, lifestyle, and environmental factors. While chocolate and coffee have been associated with better health outcomes, pinpointing the responsible specific compounds has been difficult. These foods contain multiple bioactive substances that are often consumed together, and few studies have explored their individual effects on the human epigenome, the system of chemical modifications that control gene activity and change with age. A recent study provides new insight, suggesting that theobromine, a compound naturally found in cocoa, may be associated with slower biological aging in humans. The Study: Investigating Theobromine and Epigenetic Aging in TwinsUK and KORA Cohorts The research titled “Theobromine is associated with slower epigenetic ageing,” was led by Ramy Saad from King's College London and Great Ormond Street Hospital for Children NHS Foundation Trust, alongside Jordana T. Bell from King's College London. The study was recently published in Aging-US. Full blog - https://aging-us.org/2026/01/chocolate-compound-linked-to-slower-biological-aging/ Paper DOI - https://doi.org/10.18632/aging.206344 Corresponding authors - Ramy Saad - ramy.saad@kcl.ac.uk, and Jordana T. Bell - jordana.bell@kcl.ac.uk Abstract video - https://www.youtube.com/watch?v=S0P1USM8L6E Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206344 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, theobromine, epigenetic aging, DNA methylation, metabolomics, nutrition To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — January 20, 2026 — A new #review was #published in Volume 17, Issue 12 of Aging-US on December 30, 2025, titled “Aging as a multifactorial disorder with two stages.” “This article is a contribution to the special issue of Aging celebrating the life and work of Misha Blagosklonny (more formally, Mikhail Vladimirovich Blagosklonny), who died in October 2024.” In this review, David Gems and Alexander Carver from University College London, together with Yuan Zhao from Queen Mary University of London, present a new theoretical model to explain how aging leads to the development of chronic diseases. Drawing on evolutionary theory and biological research, the authors propose that aging is driven by a combination of early-life damage and harmful genetic activity in later life. This framework helps explain why diseases such as cancer, arthritis, and infections often appear in old age and offers insight into how they might be prevented. Aging is the biggest risk factor for most chronic diseases, but the biological reasons for this association are still debated. The authors address this by introducing a two-stage model. In the first stage, individuals experience disruptions early in life, such as infections, injuries, or genetic mutations. Although the body can often contain or repair this damage, it does not fully eliminate it. In the second stage, which begins in later life, normal genetic processes begin to act in ways that are no longer beneficial. These late-life changes weaken the body's ability to contain earlier damage, allowing it to develop into disease. The review emphasizes that aging is a multifactorial process, shaped by many interacting causes rather than a single underlying mechanism. The model suggests that early-life disruptions and later-life genetic activity work together to drive age-related diseases. For example, dormant viruses can re-emerge as infections like shingles due to weakened immunity in older adults. Similarly, injuries to joints in youth can lead to osteoarthritis as tissues change with age. Inherited mutations may also remain silent for decades before contributing to conditions such as cancer or fibrosis later in life. This two-stage model builds on long-standing ideas from evolutionary biology, particularly the theory that aging occurs because natural selection has less influence in later life. The authors also draw on studies in the roundworm Caenorhabditis elegans, where early mechanical damage can lead to fatal infections in old age, suggesting similar patterns may occur in humans. Overall, this review presents a new framework for understanding how different causes of aging interact over time. By identifying two key stages, early-life damage and late-life genetic activity, it highlights potential strategies for promoting healthier aging through prevention and targeted intervention. DOI - https://doi.org/10.18632/aging.206339 Corresponding author - David Gems - david.gems@ucl.ac.uk Abstract video - https://www.youtube.com/watch?v=d4TSI4Ot3yM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206339 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, C. elegans, disease, hyperfunction, multifactorial model To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — January 16, 2026 — A new #research paper was #published in Volume 17, Issue 12 of Aging-US on December 29, 2025, titled “Age-specific DNA methylation alterations in sperm at imprint control regions may contribute to the risk of autism spectrum disorder in offspring.” The study – selected as our Editors' Choice for January, 2026 – was led by first authors Eugenia Casella and Jana Depovere, with corresponding author Adelheid Soubry from the University of Leuven. The research shows that a man's age is linked to specific changes in sperm DNA that may influence early development in children. These findings are relevant as autism diagnoses have increased while many men are becoming fathers later in life. Autism spectrum disorder is a growing public health concern affecting millions of families worldwide. The study focused on DNA methylation, a natural process that helps regulate how genes function without changing the DNA sequence itself. DNA methylation plays a key role during early development and can be sensitive to age-related biological changes. Researchers analyzed sperm samples from 63 healthy, non-smoking men between the ages of 18 and 35. DNA methylation was measured at hundreds of thousands of locations across the genome. The analysis identified more than 14,000 DNA sites where methylation levels changed with age, with most showing a gradual decrease as men got older. “To identify sperm-specific marks, we conducted an epigenome-wide association study in sperm from 63 men, using the Illumina 450K array.” While individual changes were small, their location within the genome was important. Many age-related changes occurred near imprint control regions, which help ensure that certain genes are active only from one parent. These regions are established during sperm development and are usually maintained after fertilization. Disruptions in these regions may affect how genes are regulated in offspring. Researchers found that several genes affected by age-related DNA changes have previously been linked to autism. These genes are involved in brain development, nerve communication, and early growth. Changes in their regulation may increase vulnerability to neurodevelopmental differences. Overall, the findings provide new biological insight into earlier evidence linking paternal age to child health. However, the authors note that autism is a complex condition shaped by many genetic and non-genetic factors, and no single cause has been identified. The study results suggest that age-related changes in sperm DNA may be one contributing factor. By clarifying how paternal age influences sperm biology, this research supports future studies in reproductive health as family planning increasingly shifts toward later parenthood. DOI - https://doi.org/10.18632/aging.206348 Corresponding author - Adelheid Soubry - adelheid.soubry@kuleuven.be Abstract video - https://www.youtube.com/watch?v=XC3p49Uw49w Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206348 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenome, sperm, 450K, imprinting, autism To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — January 15, 2026 — A new #research paper was #published in Volume 17, Issue 12 of Aging-US on December 1, 2025, titled “CD47 antisense oligonucleotide treatment improves glucose homeostasis and alleviates dyslipidemia in aged male mice.” Led by Taesik Gwag and Shuxia Wang from the University of Kentucky and the Lexington Veterans Affairs Medical Center, the research shows that reducing CD47 levels improves blood sugar regulation and lipid balance in older mice. These findings are significant because metabolic disorders linked to aging increase the risk of diabetes, cardiovascular disease, and other chronic conditions. The results suggest that CD47 may be a promising target for improving metabolic health during aging. As people age, metabolic problems such as insulin resistance, high cholesterol, and increased abdominal fat become more common, even without significant weight gain. CD47 is known to play roles in immune signaling and aging-related inflammation, and earlier studies have linked it to metabolic dysfunction. This study examined whether lowering CD47 activity could reverse age-related metabolic decline. Researchers treated aged male mice with an antisense oligonucleotide (ASO) designed to reduce CD47 for ten weeks. The treatment led to lower fasting blood glucose, improved glucose tolerance, and enhanced insulin sensitivity. Circulating lipid levels, including cholesterol and free fatty acids, were also reduced. Importantly, these benefits occurred without changes in overall body weight, indicating improved metabolic efficiency rather than weight loss. “Twenty-month-old male mice were treated with control ASO or CD47 ASO (25 μg/g) for 10 weeks.” One of the most notable findings was a selective reduction in visceral fat, the deep abdominal fat closely associated with metabolic disease. Fat cells in this tissue were smaller, reflecting reduced fat production within the cells rather than increased fat breakdown. This change helps explain why metabolic health improved without weight loss. Treatment also improved brown fat tissue function. Brown fat plays a key role in energy use and metabolism. Treated mice showed increased activity of genes involved in energy burning and hormone-like signaling, supporting improved whole-body glucose and lipid balance. Moreover, the liver showed improved glucose metabolism. While liver fat content was unchanged, genes involved in glucose uptake and processing were more active, further contributing to better blood sugar control. Together, these findings identify CD47 as a key regulator of age-related metabolic dysfunction. By improving glucose control, lipid balance, and fat tissue function in aged male mice, CD47 antisense therapy offers a promising path for future strategies aimed at reducing metabolic disease risk in aging populations. DOI: https://doi.org/10.18632/aging.206343 Corresponding authors: Taesik Gwag - Taesik.gwag@uky.edu and Shuxia Wang - swang7@uky.edu Abstract video: https://www.youtube.com/watch?v=U6CiiOIaIWI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206343 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

The results of studies revealed in the paper #published in Volume 17, Issue 12, titled “Age-specific DNA methylation alterations in sperm at imprint control regions may contribute to the risk of autism spectrum disorder in offspring,” indicate that advanced paternal age increases the risk of autism spectrum disorder (ASD) in children, potentially due to sperm epigenetic changes. To explore this, the authors performed an epigenome-wide association study on sperm from 63 men using the Illumina 450K array, identifying 14,622 age-related differentially methylated CpGs (DMCs), with many linked to imprinted genes and imprint control regions (ICRs). These alterations may disrupt gene expression and contribute to neurodevelopmental disorders like ASD. Several imprinted genes identified—including OTX1, PRDM16, and others—are associated with ASD, warranting further research into their role in paternal age effects on autism. Further genetic research may clarify how paternal age affects autism. Changes in DNA methylation within ICRs before conception could add to ASD's complexity. Though measured effects were small, even minor sperm epigenetic changes could influence populations as fatherhood is delayed. Preventive and educational programs could benefit public health. DOI - https://doi.org/10.18632/aging.206348 Corresponding author - Adelheid Soubry Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206348 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenome, sperm, 450K, imprinting, autism To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

As we age, every tissue in the body undergoes gradual molecular changes. A long-standing question in aging research is whether these changes follow common patterns across tissues or whether each tissue ages on its own. While DNA-based “epigenetic clocks” can estimate age accurately across different tissues, identifying consistent patterns in gene expression has been much more challenging. One reason for this difficulty is methodology. Most studies focus on whether genes increase or decrease their expression levels with age. However, genes do not function in isolation. They operate within complex networks, coordinating their activity with many others. Changes in these relationships may be important aspects of the aging process. To understand this, researchers from the University of São Paulo performed a study titled “A combination of differential expression and network connectivity analyses identifies a common set of RNA splicing and processing genes altered with age across human tissues.” Full blog - https://aging-us.org/2026/01/a-common-aging-pattern-changes-in-rna-splicing-and-processing-across-human-tissues/ Paper DOI - https://doi.org/10.18632/aging.206347 Corresponding author - Nadja C. de Souza-Pinto - nadja@iq.usp.br Abstract video - https://www.youtube.com/watch?v=A1slKwaSd6g Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206347 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, gene expression, co-expression network analysis, RNA processing To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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 — January 7, 2026 — A new #meetingreport was #published in Volume 17, Issue 12 of Aging-US on December 23, 2025, titled “Cellular senescence meets infection: highlights from the 10th annual International Cell Senescence Association (ICSA) conference, Rome 2025.” Led by Stefanie Deinhardt-Emmer from Jena University Hospital and Marco De Andrea from the University of Piemonte Orientale and the University of Turin, the report summarizes key discussions from the 10th International Cell Senescence Association conference held in Rome in September 2025. It focuses on how infections can trigger cellular senescence, a state in which cells stop dividing and release inflammatory signals. This link is important since it connects infectious diseases with aging, chronic inflammation, and lasting tissue damage. Although cellular senescence is best known for its role in aging and cancer, the meeting highlighted its emerging importance in infection biology. Researchers described how viruses and bacteria can induce senescence in infected cells and spread its effects to nearby tissues. This process, known as infection-driven senescence (IDS), can help limit pathogen replication but may also prolong inflammation and slow recovery, particularly in older adults and during chronic infections. Several sessions focused on respiratory viruses like influenza and SARS-CoV-2. Researchers showed that these viruses can promote senescence in lung cells, contributing to persistent inflammation and reduced healing. Experimental models suggested that decreasing the amount of senescent cells improved lung repair, even after the virus was cleared, offering insight into why some patients experience long-lasting respiratory symptoms. Chronic viral infections were another major theme. Human cytomegalovirus and HIV were shown to drive senescence in immune and vascular cells. In people with HIV, viral proteins were associated with biological changes resembling accelerated aging, despite effective antiviral therapy. These findings help explain why age-related conditions occur earlier and more frequently in this population. In the meeting, it was also demonstrated that senescence is not limited to viral infections. Researchers reported that the bacterium Mycobacterium abscessus induces senescence in immune cells during chronic infection. These senescent cells increased inflammation and susceptibility to further infection. Removing them reduced bacterial levels in experimental models, suggesting new directions for treating persistent bacterial disease. “Mechanistically, IDS integrates DNA damage responses, inflammatory signaling, and metabolic stress, with consistent activation of p16INK4a, p21, and NF-κB pathways.” Across the conference, speakers discussed therapies that either remove senescent cells or reduce their harmful inflammatory signals. These approaches, known as senolytic and senomorphic strategies, showed promise in preclinical studies as potential tools to limit infection-related tissue damage and chronic inflammation. Overall, the meeting report presents infection-driven senescence as a unifying concept linking infection, immunity, and aging. The discussions at ICSA 2025 highlight a growing field with important implications for understanding chronic disease and the long-term health effects of infections. DOI: https://doi.org/10.18632/aging.206349 Abstract video: https://www.youtube.com/watch?v=gOHEBJs7DIc Connect with us on social media: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc

BUFFALO, NY — January 5, 2026 — A new #research paper featured as the #cover of Volume 17, Issue 12 of Aging-US was #published on December 22, 2025, titled “A combination of differential expression and network connectivity analyses identifies a common set of RNA splicing and processing genes altered with age across human tissues.” In this study by Caio M.P.F. Batalha from the University of São Paulo, André Fujita from the University of São Paulo and Kyushu University, and Nadja C. de Souza-Pinto also from the University of São Paulo, researchers investigated how gene activity changes with age across multiple human tissues. They found that many tissues share common aging-related alterations in genes involved in RNA splicing and RNA processing. These findings are important because RNA processing is essential for accurate protein production, and disruptions in this process are linked to aging and disease. Aging affects all tissues, yet identifying molecular changes that are shared across the body has remained challenging. To address this, researchers moved beyond traditional approaches that focus exclusively on changes in gene expression levels. They also analyzed how genes alter their patterns of interaction within regulatory networks, capturing age-related changes that are not evident from expression data alone. “Gene expression data (in TPM – transcripts per million) were obtained from the Genotype-Tissue Expression (GTEx) project.” Using RNA sequencing data from nearly one thousand human donors aged 20 to 70, the research team analyzed eight tissues, including blood, brain, heart, skin, and muscle. The results showed that many aging-related changes become evident only when gene network behavior is considered. When gene expression and network connectivity were analyzed together, a consistent group of genes emerged across tissues, most of which were linked to RNA splicing and RNA processing, key steps in the production of functional proteins. The study also revealed that these RNA-related genes are highly interconnected at the protein level. Many of them form known protein complexes, including components of the spliceosome, which plays a central role in RNA maturation. With age, the interactions among these genes tend to reorganize in similar ways across tissues, pointing to a shared biological response rather than independent, tissue-specific effects. In addition to RNA processing, the researchers observed age-related changes in pathways involved in managing damaged RNAs and proteins, including protein degradation, autophagy, and DNA damage response mechanisms. These pathways support cellular quality control and help limit the accumulation of molecular errors that increase with age. Overall, this study identifies RNA splicing and RNA processing as central, conserved features of human aging across tissues. It also demonstrates that network-based approaches provide a more complete view of the aging transcriptome, offering new insights into age-related biological changes and potential directions for aging research. DOI - https://doi.org/10.18632/aging.206347 Corresponding author - Nadja C. de Souza-Pinto - nadja@iq.usp.br Abstract video - https://www.youtube.com/watch?v=A1slKwaSd6g Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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 — December 30, 2025 — A new #research paper was #published in Volume 17, Issue 11 of Aging-US on November 26, 2025, titled “Epigenetic aging signatures and age prediction in human skeletal muscle.” In this study, first author Soo-Bin Yang and corresponding author Hwan Young Lee from Seoul National University College of Medicine investigated how DNA methylation patterns in skeletal muscle change with age. Their findings offer a new and highly accurate method for estimating a person's age, with potential applications in forensic science and aging research. Skeletal muscle is essential for movement, energy balance, and physical strength, functions that become more important to monitor as people age. This study improves our understanding of how muscle tissue changes over time at the molecular level. Unlike previous research, which mainly analyzed living individuals of European descent, this study used postmortem samples from an Asian population. “We analyzed DNA methylation profiles from 103 pectoralis major muscle samples from autopsies of South Korean individuals (18–85 years) using the Infinium EPIC array.” The researchers analyzed DNA from over 100 pectoralis major muscle samples taken from individuals aged 18 to 85. They identified 20 DNA methylation sites, called CpGs, that were strongly associated with age. These CpGs were found in genes involved in muscle function, stress response, metabolism, and age-related diseases. Using these markers, the team built two machine learning models to predict age: one using Next-Generation Sequencing (NGS) and another using Single Base Extension (SBE). Both models were highly accurate, with average prediction errors between 3.8 and 5.5 years. The new “epigenetic clocks” outperformed existing age-prediction models designed for other tissue types. However, when applied to cardiac and uterine muscle, these models showed much lower accuracy, reinforcing the need for tissue-specific approaches in molecular age estimation. Beyond predicting age, the study also provides insight into how DNA methylation may affect muscle aging. Several of the identified CpGs were located in regions that regulate gene expression, being associated with a reduction of it in older muscle samples. Some of the affected genes are associated with sarcopenia, an age-related loss of muscle mass and strength. Overall, this study introduces two reliable and cost-effective methods to estimate age from skeletal muscle, even when the DNA is partially degraded, making it especially useful in forensic settings. It also offers a path forward for developing future therapies that may slow age-related muscle decline and highlights how skeletal muscle aging can differ depending on population, tissue type, and anatomical location. DOI - https://doi.org/10.18632/aging.206341 Corresponding author - Hwan Young Lee - hylee192@snu.ac.kr Abstract video - https://www.youtube.com/watch?v=1i6Ua0cceMU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206341 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, skeletal muscle, age, DNA methylation, next generation sequencing, single base extension To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — December 23, 2025 — A new #research paper was #published in Volume 17, Issue 11 of Aging-US on November 25, 2025, titled “A natural language processing–driven map of the aging research landscape.” In this study, Jose Perez-Maletzki from Universidad Europea de Valencia and Universitat de València, together with Jorge Sanz-Ros from Stanford University School of Medicine, used artificial intelligence (AI) to analyze a century of global aging research, revealing shifts in focus and highlighting underexplored areas. The team analyzed over 460,000 scientific abstracts published between 1925 and 2023 to identify key themes, trends, and research gaps in the study of aging. Their goal was to provide a comprehensive, unbiased view of how the field has evolved and where future research could have the greatest impact. The study found that aging research has moved from basic cellular studies and animal models to a growing focus on clinical topics, particularly age-related diseases such as Alzheimer's and dementia. Using natural language processing and machine learning, the researchers grouped publications into thematic clusters and tracked how interest in each topic changed over time. “By integrating Latent Dirichlet Allocation (LDA), term frequency-inverse document frequency (TF-IDF) analysis, dimensionality reduction and clustering, we delineate a comprehensive thematic landscape of aging research.” One key finding was the growing separation between basic biological studies and clinical research. While both areas have grown significantly, they often progress independently with limited overlap. Clinical studies tend to focus on geriatrics, healthcare, and neurodegenerative diseases, while basic science emphasizes cellular mechanisms such as oxidative stress, telomere shortening, mitochondrial dysfunction, and senescence. The authors note that this lack of integration limits the translation of laboratory discoveries into medical applications. The study also showed that some emerging topics, such as autophagy, RNA biology, and nutrient sensing, are expanding rapidly but remain separated from clinical applications. In contrast, long-established links, such as those between cancer and aging, remain strong. The analysis also highlighted that potentially important associations, such as those between mitochondrial dysfunction and senescence or epigenetics and autophagy, are rarely studied and may be new research opportunities. This AI-driven analysis offers a new way to guide future research by identifying how different areas of aging science are interconnected or isolated. It also highlights how research priorities may be shaped by policy or funding trends, as seen in the heavy focus on Alzheimer's disease. As the global population continues to age, understanding how biological processes relate to clinical outcomes is critical. This study not only offers a historical map of aging science but also serves as a tool to support more connected, interdisciplinary, and effective future research. DOI - https://doi.org/10.18632/aging.206340 Corresponding author - Jorge Sanz-Ros - jsanzros@stanford.edu Abstract video - https://www.youtube.com/watch?v=O4dJUGQ2ZcU Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — December 19, 2025 — A new #research paper was #published in Volume 17, Issue 11 of Aging-US on November 18, 2025, titled “Epigenetic age predicts depressive symptoms during the COVID-19 pandemic in the Canadian Longitudinal Study on Aging: importance of biological sex.” This study, led by Cindy K. Barha of the University of Calgary and the University of British Columbia, along with Teresa Liu-Ambrose of the University of British Columbia, found that older women with a younger biological age measured years before the COVID-19 pandemic experienced a greater increase in depressive symptoms during the early lockdown period. These findings could help shape future mental health strategies, particularly for women with high emotional or caregiving demands. Epigenetic age is a biological marker that reflects how the body is aging and may differ from a person's actual age. Using long-term data from the Canadian Longitudinal Study on Aging (CLSA), the researchers investigated whether epigenetic age could predict changes in mental health during a major public health crisis. The study included over 600 adults, with an average baseline age of 63, and used two widely accepted epigenetic clocks, the DNAmAge and the Hannum Age, to estimate biological age. Depressive symptoms were tracked at four time points between 2012 and 2020, including during the height of the pandemic. “The mean participant chronological age at study entry was 63±10 years (46% female).” The analysis showed that in women, a younger biological age predicted a greater rise in depression during the early phase of the COVID-19 pandemic. This was not observed in men or in individuals with older biological ages. The study challenges the common belief that a younger biological age always signals better mental or physical resilience. The researchers suggest that women with younger biological profiles may have been more socially or professionally active before the pandemic. When lockdowns disrupted daily routines and social connections, these individuals may have experienced more emotional distress. Additional factors, such as reduced physical activity, loss of routine, and decreased social interaction, known to affect both mental health and biological aging, may have had a stronger emotional effect on this group. The findings highlight the importance of considering biological sex when studying how aging affects mental well-being during stressful events. Although the study has some limitations, including the time gap between biological age measurement and the pandemic, it gives valuable insights into how biological and social factors interact during periods of crisis. Future research could use epigenetic clocks to better identify individuals at greater risk of mental health challenges during large-scale public health emergencies. Overall, this study adds to the growing field of social epigenetics and suggests that biological age may support more targeted public health planning, especially for older adults. DOI - https://doi.org/10.18632/aging.206337 Corresponding author - Teresa Liu-Ambrose - teresa.ambrose@ubc.ca Abstract video - https://www.youtube.com/watch?v=DVm78jKsdkY Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY— December 17, 2025 — We are pleased to announce that we have officially joined ResearchGate, the professional network for scientists and researchers. This collaboration enhances the visibility, accessibility, and impact of research published in Aging-US among the global scientific community. By integrating ResearchGate, Aging-US offers authors and readers an additional channel to discover, share, and discuss cutting-edge findings in aging research. The journal's presence on the platform includes a dedicated profile, article listings, author profiles, and metrics that help track readership and engagement. As the field of aging research continues to grow rapidly, it is essential that high-quality studies are easy to find, access, and share. Joining ResearchGate allows Aging-US authors to connect their work with a wider network of peers, fostering collaboration, advancing understanding of the biology of aging, and helping translate discoveries into better health outcomes. ResearchGate hosts millions of researchers worldwide and provides tools for sharing publications, asking and answering research questions, and discovering new collaborators across institutions and disciplines. Aging-US's participation on the platform reinforces its commitment to open scientific dialogue and timely dissemination of rigorously reviewed aging research. Authors publishing in Aging-US can now: -Link their publications directly to their ResearchGate profiles. -Track reads, recommendations, and citations through the platform's analytics. -Engage with other scientists interested in aging, geroscience, and translational research. Readers and researchers can follow Aging-US on ResearchGate to stay updated on newly published articles, special issues, and calls for papers. To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — December 16, 2025 — A new #research paper was #published in Aging-US on December 10, 2025, titled “Theobromine is associated with slower epigenetic ageing.” In this study, led by Ramy Saad from King's College London and Great Ormond Street Hospital for Children NHS Foundation Trust, alongside Jordana T. Bell from King's College London, researchers found that higher levels of theobromine, a natural compound found in cocoa, are associated with slower biological aging in humans. The findings suggest that theobromine may support healthy aging. Epigenetic aging refers to biological changes that affect how genes function over time. It is measured using blood-based markers such as DNA methylation and telomere length, which together provide a more accurate picture of aging than chronological age. In this work, researchers analyzed data from two large European studies. In 509 women from the TwinsUK cohort, they found that higher blood levels of theobromine were associated with slower aging, especially based on GrimAge, an epigenetic clock that predicts the risk of age-related disease and early death. The results were confirmed in 1,160 men and women from the German KORA study. “We initially tested for the association between six metabolites found in coffee and cocoa, and epigenetic measures of ageing in blood samples from 509 healthy females from the TwinsUK cohort (median age = 59.8, IQR = 12.81, BMI = 25.35).“ Importantly, theobromine's effects were independent of related compounds such as caffeine. Even after adjusting for these other substances and different lifestyle factors, the association with slower aging remained strong. The study also associated higher theobromine levels with longer telomeres, another marker of healthy aging. While theobromine is commonly found in cocoa and chocolate, the study does not suggest increasing chocolate intake. However, it highlights the potential of everyday dietary components such as theobromine to influence aging. These findings support growing evidence that certain plant-based compounds may play a role in promoting long-term health. By identifying a connection between theobromine and slower biological aging, the study opens new directions for research into nutritional strategies for healthy aging. DOI - https://doi.org/10.18632/aging.206344 Corresponding authors - Ramy Saad - ramy.saad@kcl.ac.uk, and Jordana T. Bell - jordana.bell@kcl.ac.uk Abstract video - https://www.youtube.com/watch?v=S0P1USM8L6E Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206344 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, theobromine, epigenetic aging, DNA methylation, metabolomics, nutrition To learn more about the journal, visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — December 12, 2025 — A new #research paper was #published in Volume 17, Issue 11 of Aging-US on November 14, 2025, titled “Methylglyoxal-induced glycation stress promotes aortic stiffening: putative mechanistic roles of oxidative stress and cellular senescence.” The study was led by first authors Parminder Singh of the Buck Institute for Research on Aging and Ravinandan Venkatasubramanian of the University of Colorado Boulder, with senior contributions from corresponding authors Pankaj Kapahi (Buck Institute for Research on Aging) and Zachary S. Clayton (University of Colorado Boulder and University of Colorado Anschutz Medical Campus). The researchers investigated how methylglyoxal (MGO), a toxic byproduct that builds up in blood vessels with age or metabolic dysfunction like diabetes, contributes to artery stiffening. Their findings are especially important to aging and diabetes-related cardiovascular risk. Aortic stiffening, which reduces the flexibility of the body's largest artery, is a key predictor of cardiovascular disease in older adults. The research team used young and aged mice to study how MGO affects vascular health. In young mice, chronic exposure to MGO increased aortic stiffness by 21%. However, when treated with Gly-Low, a supplement containing natural compounds such as nicotinamide and alpha-lipoic acid, this stiffening was completely prevented. Gly-Low also reduced the buildup of MGO and its harmful byproducts, particularly MGH-1, in both blood and tissue. “Aortic stiffness was assessed in vivo via pulse wave velocity (PWV) and ex vivo through elastic modulus.” The research showed that MGO's damage goes beyond structural changes. It also caused the endothelial cells that line blood vessels to enter senescence, a state in which cells stop dividing and begin releasing inflammatory signals. This led to lower levels of nitric oxide, a molecule essential for blood vessel relaxation. In human vascular cells in lab culture, Gly-Low reversed these aging-like changes and restored nitric oxide production. In older mice, which naturally develop stiffer arteries, Gly-Low treatment during four months significantly reduced stiffness and lowered MGO and MGH-1 levels. This suggests that Gly-Low may help slow or even reverse vascular aging by reducing glycation stress. The study also identified the glyoxalase-1 pathway as a critical mechanism. This is a natural detox system that helps clear harmful molecules like MGO. Gly-Low appeared to boost this pathway. When the pathway was chemically blocked, Gly-Low's protective effects disappeared, confirming its role in the process. Overall, the findings highlight glycation stress as a modifiable contributor to vascular aging. The results suggest that natural compound-based therapies, like Gly-Low, may offer a potential strategy to protect arteries from age- and diabetes-related damage. DOI - https://doi.org/10.18632/aging.206335 Corresponding authors: Pankaj Kapahi - pkapahi@buckinstitute.org; Zachary S. Clayton - Zachary.Clayton@cuanschutz.edu Abstract video: https://www.youtube.com/watch?v=i_rtq8eIb8c Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 X - https://twitter.com/AgingJrnl Facebook - https://www.facebook.com/AgingUS/ Instagram - https://www.instagram.com/agingjrnl/ LinkedIn - https://www.linkedin.com/company/aging/ Reddit - https://www.reddit.com/user/AgingUS/ Pinterest - https://www.pinterest.com/AgingUS/ YouTube - https://www.youtube.com/@Aging-US Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Treating aggressive cancers that do not respond to standard therapies remains one of the most significant challenges in oncology. Among these are basal-like breast cancers (BLBC), which lack hormone receptors and HER2 amplification. This makes them unsuitable for many existing targeted treatments. As a result, therapeutic options are limited, and patient outcomes are often poor. One emerging strategy is to induce senescence, a state in which cancer cells permanently stop dividing but remain metabolically active. This approach aims to slow or stop tumor growth without killing the cells directly. Although promising, the clinical application of senescence-based therapies has been limited by several challenges. Senescence is typically identified using biomarkers such as p16, p21, and beta-galactosidase activity. However, these markers are often already present in aggressive cancers like BLBC (Sen‑Mark+ tumors), making it difficult to determine whether a treatment is truly inducing senescence or merely reflecting the tumor's existing biology. Moreover, conventional screening methods may mistake reduced cell growth for senescence, cell death, or temporary growth arrest, leading to inaccurate assessments. This is especially problematic in large-scale drug screening, where thousands of compounds must be evaluated quickly and reliably. To overcome these issues, researchers from Queen Mary University of London and the University of Dundee have developed a new machine learning–based method to improve the detection of senescence in cancer cells. Their findings were recently published in Aging-US. The Study: Developing the SAMP-Score The study, titled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16-positive cancer cells,” was led by Ryan Wallis and corresponding author Cleo L. Bishop from Queen Mary University of London. This paper was featured on the cover of Aging-US Volume 17, Issue 11, and highlighted as our Editors' Choice. Full blog - https://aging-us.org/2025/12/using-machine-learning-to-identify-senescence-inducing-drugs-for-resistant-cancers/ Paper DOI - https://doi.org/10.18632/aging.206333 Corresponding author - Cleo L. Bishop - c.l.bishop@qmul.ac.uk Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206333 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, SAMP-Score, senescence, senescent marker positive cancer cells, Sen-Mark+, machine learning, pro-senescence, high-throughput compound screening To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

The paper featured on the cover of this issue of Aging-US, published on October 30, 2025, entitled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16-positive cancer cells,” represents an important methodological and conceptual advance at the interface of senescence biology, imaging and drug discovery. In this study, led by first author Ryan Wallis and corresponding author Cleo L. Bishop (Queen Mary University of London), the authors introduce SAMP-Score, a machine-learning–based framework designed to identify bona fide senescence induction in cancer cells where canonical markers fail. This is a timely and much-needed contribution to the field. Therapy-induced senescence has emerged as a powerful strategy to restrain tumor growth, yet its reliable detection in cancer cells remains a major bottleneckIn these contexts, cells often already display features associated with cellular aging, rendering conventional senescence markers ambiguous or misleading. Distinguishing true senescence from toxicity, stress responses or baseline “aged” phenotypes is therefore a critical unmet need. Rather than relying on predefined molecular readouts, the authors take a different approach and train a machine-learning model to recognize senescence-associated morphological profiles (SAMPs) which are subtle but reproducible changes in cellular architecture captured through high-content microscopy. By learning directly from image-based phenotypes, SAMP-Score is able to identify senescence with a level of precision that is difficult to achieve using marker-based strategies alone. The strength of the platform demonstrated through a large-scale screen of over 10,000 novel chemical entities in p16-positive basal-like breast cancer cells. From this screen, the compound QM5928 emerged as a robust inducer of senescence across multiple cancer models, notably without inducing cytotoxicity. Importantly, QM5928 retains activity in cellular contexts that are resistant to CDK4/6 inhibition, including palbociclib-refractory, p16-high tumors. Mechanistically, the authors show that QM5928 promotes nuclear relocalization of p16, consistent with a functional engagement of cell-cycle arrest pathways. These nuanced phenotypic changes would likely have gone undetected without the resolution and discrimination provided by SAMP-Score, underscoring the platform's ability to separate true senescence from confounding cellular states. This work exemplifies how machine learning and quantitative imaging can be harnessed to solve long-standing problems in senescence research, moving the field beyond binary marker expression toward phenotype-driven classification. Beyond its immediate relevance for cancer therapy, SAMP-Score offers a broadly applicable framework for senescence-based screening efforts across biological contexts. DOI - https://doi.org/10.18632/aging.206333 Corresponding author - Cleo L. Bishop - c.l.bishop@qmul.ac.uk Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206333 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media at: Bluesky - https://bsky.app/profile/aging-us.bsky.social ResearchGate - https://www.researchgate.net/journal/Aging-1945-4589 Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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 — December 8, 2025 — A new #research paper was #published in Volume 17, Issue 11 of Aging-US on September 12, 2025, titled “Infusion of blood from young and old mice modulates amyloid pathology.” This study was led by co-first authors Matias Pizarro from Universidad Adolfo Ibáñez and Ruben Gomez-Gutierrez from The University of Texas Health Science Center at Houston, alongside corresponding authors Claudia Duran-Aniotz from Universidad Adolfo Ibáñez and Rodrigo Morales from The University of Texas Health Science Center at Houston and Universidad Bernardo O'Higgins. The goal was to investigate how blood from young and old mice influences Alzheimer's-related changes in a transgenic mouse model. The findings indicate that age-dependent circulating factors can either worsen or mitigate brain changes associated with dementia, highlighting blood and its components as potential therapeutic targets. Alzheimer's disease is a progressive neurodegenerative disorder characterized by misfolded amyloid proteins, inflammation, and gradual cognitive decline, with aging as its main risk factor. In this work, whole blood from young adult or very old wild-type mice was repeatedly infused into Tg2576 mice, a well-established model of amyloid accumulation and memory impairment. Over several months, recipient mice received 30 weekly blood infusions, followed by behavioral testing and detailed neuropathological analyses. “Tg2576 mice express the human APP harboring the Swedish mutation.” Mice that received blood from old donors performed worse in both short- and long-term spatial memory tasks than mice infused with young blood, suggesting that aged blood contains factors that impair cognition. When the team examined brain tissue, they found more cortical amyloid deposits detected by a specific antibody in mice treated with old blood, while overall amyloid levels measured biochemically did not change, suggesting differences in plaque type or compactness rather than total amount. The expression of amyloid precursor protein in the brain was also higher after old-blood infusion, which may partly explain the shift in amyloid pathology.​ Despite these changes in plaques and memory, classical markers of astrocyte activation, a sign of brain inflammation, did not differ between groups, pointing to more subtle molecular shifts. A broad proteomic analysis of brain samples revealed dysregulation of proteins involved in synapse formation, calcium signaling, and the endocannabinoid system, pathways important for neuronal communication and plasticity. Among them, the calcium channel–related protein CACNA2D2 and the signaling protein BRAF were increased in mice that received old blood, confirming that aged blood circulation can reshape key signaling networks linked to neuronal function and degeneration. Overall, this study supports the idea that blood is not just a passive carrier but a powerful modulator of brain health during aging and disease. While young blood has been associated in previous work with improved synaptic function and reduced amyloid and tau changes, this study emphasizes the harmful impact of old blood, particularly on cortical amyloid patterns and memory. The identification of CACNA2D2 and BRAF as potential mediators of these effects suggests new avenues for targeting blood-borne factors or downstream brain pathways to slow or modify Alzheimer's-related decline. DOI - https://doi.org/10.18632/aging.206319 Corresponding authors - Claudia Duran-Aniotz - Claudia.Duran@uai.cl, and Rodrigo Morales - Rodrigo.MoralesLoyola@uth.tmc.edu Abstract video - https://www.youtube.com/watch?v=zsBDSAipH3w To learn more about the journal, visit https://www.Aging-US.com​​. MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — December 3, 2025 — A new #essay was #published in Volume 17, Issue 11 of Aging-US on November 19, 2025, titled “On the intergenerational transfer of ideas in aging and cancer research: from the hypothalamus according to V.M. Dilman to the mTOR protein complex according to M.V. Blagosklonny.” In this work, Aleksei G. Golubev from the N.N. Petrov National Medical Research Center of Oncology reflects on the legacy of two influential Russian scientists, Vladimir M. Dilman and his son Mikhail V. Blagosklonny, who each introduced groundbreaking ideas about aging and cancer. Drawing from his own experience working in Dilman's lab, Golubev explores how their ideas remain deeply relevant to today's scientific understanding. The essay connects Dilman's “elevation theory” with Blagosklonny's “hyperfunction theory,” two frameworks that challenge the conventional view of aging as a process of decline. Instead, both propose that aging results from continued biological processes that once supported growth but eventually become harmful when left unchecked. Dilman believed that aging begins with reduced sensitivity in the hypothalamus, a brain region that regulates the body's balance. This desensitization disrupts metabolism and hormone levels, setting the stage for many chronic illnesses. Decades later, Blagosklonny expanded on this idea at the molecular level. Central to his theory is the mTOR protein complex, which regulates growth and metabolism and is now a major focus in aging research. Golubev also explores the historical and personal connections between the two scientists. Dilman, an endocrinologist trained in the Soviet Union, and Blagosklonny, a molecular biologist educated during the post-Soviet period, represent two generations shaped by a shared scientific tradition. “Dilman's scientific legacy is not as well recognized as it should be, partly due to bias in citation practices.” The essay also draws attention to a troubling trend in science: the tendency to overlook early contributions, especially from non-Western scholars. Many of Dilman's insights, such as the connection between high blood sugar, insulin resistance, and cancer, have since been validated by modern tools, yet his work is rarely cited. Golubev points out how citation practices, language barriers, and historical isolation have contributed to this lack of recognition. Finally, Golubev encourages the scientific community to look back and acknowledge the foundational work that shaped modern aging science. It also highlights the importance of cross-generational knowledge in moving science forward. By tracing the intellectual journey from hormonal regulation in the brain to molecular pathways in cells, this essay demonstrated the relevance of old ideas in a new biological era. DOI - https://doi.org/10.18632/aging.206338 Corresponding author - Aleksei G. Golubev - lxglbv@rambler.ru Abstract video - https://www.youtube.com/watch?v=LvrdghTKGws Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206338 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, gerontology, history of science, hyperfunction, mTOR, hypothalamus, cancer, metabolism, immunity To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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 — December 1, 2025 — A new #research paper featured on the #cover of Volume 17, Issue 11 of Aging-US was #published on October 30, 2025, titled “SAMP-Score: a morphology-based machine learning classification method for screening pro-senescence compounds in p16 positive cancer cells.” In this study led by first author Ryan Wallis along with corresponding author Cleo L. Bishop, from Queen Mary University of London, researchers developed a machine learning tool to identify compounds that induce cancer cells into senescence. The tool, called SAMP-Score, offers a new strategy for drug discovery in cancers with poor treatment options like basal-like breast cancer. Senescence is a process where damaged or aged cells stop dividing. In cancer therapy, inducing senescence is an approach to control tumor growth. However, it is difficult to detect true senescence in cancer cells that already appear aged. These cancers, often called Sen-Mark+ cancers, include basal-like breast cancer and typically lack reliable markers to confirm senescence. SAMP-Score was designed to address this problem. Instead of relying on traditional markers, the researchers built a machine learning model trained to recognize patterns based on senescent cells' shape and structure under a microscope. These visual patterns, known as senescence-associated morphological profiles (SAMPs), allowed the model to distinguish real signs of aging from other effects such as toxicity or normal variation. By analyzing thousands of cell images, the model learned to classify whether a cell had truly entered senescence. “To demonstrate the potential application of SAMP-Score in p16 positive cancer therapeutic discovery, we assessed a diversity screen of 10,000 novel chemical entities in MB-468 cells (p16 positive BLBC).” The team used SAMP-Score to screen more than 10,000 experimental compounds. One compound, QM5928, consistently triggered senescence in several cancer cell types without killing them, making it a promising candidate for further study. Importantly, it worked in cancers resistant to known drugs like palbociclib, which are often ineffective in cancers with high p16 expression like basal-like breast cancer. Further analysis revealed that QM5928 caused the p16 protein to move into the nucleus of cancer cells, a possible sign that the protein is helping stop cell division. This subtle effect was only detectable using the detailed imaging and analysis made possible by SAMP-Score, highlighting the tool's ability to distinguish true senescence from toxic responses and making it a powerful resource in cancer drug discovery. By combining machine learning with high-resolution imaging, this study introduces a new way to find and evaluate cancer therapies. SAMP-Score could accelerate efforts to develop treatments that exploit the body's natural aging processes to fight cancer, especially for patients with resistant tumors. The tool is openly available at GitHub, making it accessible for other researchers exploring senescence-based cancer therapies. DOI - https://doi.org/10.18632/aging.206333 Corresponding author - Cleo L. Bishop - c.l.bishop@qmul.ac.uk Abstract video - https://www.youtube.com/watch?v=qXI_KI3EgHE Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit 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/@Aging-US 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

Interest in healthier, longer lives is rising, supported by recent scientific advances in aging research. But turning those discoveries into everyday healthcare solutions remains a work in progress. In this landscape, longevity clinics have attracted attention as personalized alternatives to traditional medicine. What Are Longevity Clinics? Longevity clinics are private centers offering tailored programs designed to improve long-term health and slow biological aging. Using advanced diagnostics such as genetic sequencing, full-body imaging, and blood tests, they develop personalized plans that may include exercise, nutrition, hormone therapy, or experimental treatments. Frequently found in countries like the United States, Switzerland, and the United Arab Emirates, these clinics reflect a growing global interest in preventive healthcare, though their high costs and scientific credibility remain subjects of debate. The Editorial “Longevity clinics: between promise and peril,” an editorial by Marco Demaria, Editor-in-Chief of Aging-US, from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), was published in Aging-US (Volume 17, Issue 10). Full blog - https://aging-us.org/2025/11/longevity-clinics-balancing-innovation-with-regulation/ Paper DOI - https://doi.org/10.18632/aging.206330 Corresponding author - Marco Demaria — m.demaria@umcg.nl Abstract video - https://www.youtube.com/watch?v=Bt84xBdii0s Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206330 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, longevity clinics, biomarkers, frailty, senescence To learn more about the journal, visit 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/@Aging-US 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 — November 25, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 13, 2025, titled “Hospitalization with infections and risk of Dementia: a systematic review and meta-analysis.” This large-scale meta-analysis, led by first author Wei Yu Chua from the National University of Singapore and corresponding author Eng-King Tan from the National Neuroscience Institute and Duke-NUS Medical School in Singapore, shows that adults hospitalized with infections have a significantly higher risk of developing dementia. The findings are especially important as global populations grow older and hospitalizations for infections increase, highlighting a potential new approach for dementia prevention. “Out of 1900 studies that were screened initially, 16 studies comprising 4,266,276 patients were included for analysis.” The researchers analyzed data from over 4 million individuals across 16 studies, making this study the most comprehensive review to date on the association between infection-related hospital stays and long-term brain health. The results showed that being hospitalized for an infection raised the risk of all-cause dementia by 83%. Among the types of infections studied, sepsis carried the highest risk, followed by pneumonia, urinary tract infections, and skin or soft tissue infections. The risk of developing vascular dementia was notably higher than that of Alzheimer's disease. One possible explanation for the association between infections and dementia is that infections trigger systemic inflammation that may reach the brain. Inflammatory molecules can cross the blood-brain barrier, potentially leading to the buildup of damaging proteins and the death of brain cells. This process may be more severe in older adults, whose immune systems are often slower to respond and recover. The study also suggests that even a single infection-related hospitalization can speed up cognitive decline, especially in individuals already at higher risk. Importantly, the risk of dementia was greatest within the first year following an infection but remained elevated for many years afterward. In fact, studies with follow-ups longer than a decade showed even stronger associations. These results suggest the need for early cognitive monitoring after hospital discharge, particularly in older adults recovering from infections. These findings have important implications for healthcare systems, particularly those serving aging populations, and underscore the lasting impact that infections can have on the brain. This research highlights the importance of looking beyond genetics and lifestyle for prevention strategies. With over 50 million people affected by dementia worldwide and annual care costs in the U.S. exceeding $300 billion, identifying new and preventable risk factors is critical. Reducing infections, improving hospital care, and monitoring brain health after illness may offer promising ways to protect cognitive function in aging populations. DOI - https://doi.org/10.18632/aging.206329 Corresponding author - Eng-King Tan - tan.eng.king@singhealth.com.sg Abstract video - https://www.youtube.com/watch?v=uyv5VHHHIA4 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206329 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, visit 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/@Aging-US 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 — November 20, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 10, 2025, titled “Developmental arrest rate of an embryo cohort correlates with advancing reproductive age, but not with the aneuploidy rate of the resulting blastocysts in good prognosis patients: a study of 25,974 embryos.” In this large-scale study, Andres Reig of the IVIRMA Global Research Alliance and Robert Wood Johnson Medical School, along with Emre Seli of the IVIRMA Global Research Alliance and Yale School of Medicine, investigated how female age and chromosomal abnormalities affect embryo development in patients undergoing in vitro fertilization (IVF). They found that embryo developmental arrest (EDA) becomes more common as women age. However, this arrest is not directly associated with the presence of chromosomal errors in the embryos that continue to develop. These findings could help improve fertility counseling and treatment strategies. The researchers analyzed 25,974 embryos from 1,928 IVF cycles, all from patients with a good chance of success. The study showed that the percentage of embryos that stopped developing before reaching the blastocyst stage increased with age: from 33% in women under 35 to 44% in those over 42. Despite this rise, the rate of chromosomal abnormalities, known as aneuploidy, in the embryos that did reach the blastocyst stage did not show a strong connection with the rate of arrest after adjusting for age. This distinction is important because both developmental arrest and aneuploidy reduce the number of embryos suitable for transfer. But this study suggests they are caused by different biological processes. In other words, an embryo may stop developing even if it has the correct number of chromosomes, and some embryos with chromosomal abnormalities may still grow to the blastocyst stage. “A very weak positive correlation was identified between EDA rate and the rate of aneuploidy (r: 0.07, 95% CI 0.03–0.11; R2: 0.00, p < 0.01) when evaluating all cohorts.” The authors suggest that other factors, such as the health of the egg's mitochondria or mutations in maternal-effect genes, may explain why some embryos stop developing. These insights could help researchers identify new ways to improve embryo quality, especially for older women undergoing IVF. Importantly, the study focused on embryos that developed far enough to be tested, which helped avoid technical problems that come with analyzing arrested embryos directly. This approach allowed for more reliable comparisons across age groups and embryo quality. Overall, the study highlights the importance of maternal age as a key factor in embryo development, independent of chromosomal results. It also opens new directions for research, aiming to better understand why embryos fail to develop and how this knowledge might lead to improved fertility treatments in the future. DOI - https://doi.org/10.18632/aging.206328 Corresponding author - Emre Seli - emre.seli@yale.edu Abstract video - https://www.youtube.com/watch?v=g0oS3HBNmuQ Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206328 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, ovarian aging, reproductive aging, embryonic arrest, embryonic aneuploidy, developmental arrest To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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 — November 18, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 3, 2025, titled “Growth hormone excess drives liver aging via increased glycation stress.” In this study, led by first author Parminder Singh alongside with corresponding authors Pankaj Kapahi from the Buck Institute for Research on Aging and Andrzej Bartke from Southern Illinois University School of Medicine, researchers investigated how elevated growth hormone (GH) levels contribute to liver aging and dysfunction. They found that excess GH disrupts liver metabolism in ways that resemble aging-related liver damage. The study suggests that managing glycation stress may help prevent or treat liver diseases linked to abnormal hormone levels. Excess GH is known to cause different disorders, but its long-term impact on internal organs like the liver has remained unclear. To address this, researchers used a mouse model engineered to overproduce bovine GH and examined how chronic hormone exposure affects liver function over time. “Pathological conditions such as acromegaly or pituitary tumors result in elevated circulating GH levels, which have been implicated in a spectrum of metabolic disorders, potentially by regulating liver metabolism.” The team found that young mice with GH overexpression showed molecular and cellular patterns similar to those in naturally aged livers. In both groups, genes involved in metabolism were suppressed, while those linked to immune and inflammatory responses were activated. On one hand, the metabolic changes were associated with the buildup of advanced glycation end products, harmful compounds formed when sugars attach to proteins or fats without proper regulation. On the other hand, the immune and inflammatory changes reflected a process known as “inflammaging,” a form of chronic, low-grade inflammation commonly associated with aging. By revealing the overlap between hormone-driven and age-related liver dysfunction, the study provides new insight into how GH may accelerate aging processes. Importantly, the team showed that reducing glycation stress can reverse many of these negative effects. Mice treated with a compound that lowers glycation levels demonstrated improved liver health, reduced insulin resistance, and enhanced physical function. This intervention also corrected several abnormal genetic patterns caused by excess GH. The findings point to a potential therapeutic strategy for liver diseases associated with aging and hormonal imbalances. Overall, this research identifies glycation and its byproducts as key contributors to liver damage caused by excess GH. It suggests that targeting glycation could offer broad therapeutic benefits, not only for hormone-related conditions but also for supporting liver health during aging. DOI - https://doi.org/10.18632/aging.206327 Corresponding authors - Andrzej Bartke - abartke@siumed.edu and Pankaj Kapahi - pkapahi@buckinstitute.org Abstract video - https://www.youtube.com/watch?v=6v8xi5muLwA Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206327 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, growth hormone, glycation stress, Gly-Low To learn more about the journal, visit 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/@Aging-US 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. Amparo Santamaria from the Reproductive Hematology Unit at the IVIRMA Alicante Clinic in Spain joins Dr. Evgeniy Galimov to discuss her #research paper #published in Volume 17, Issue 6 of Aging-US, titled “Enhancing oocyte activation in women with ovarian failure: clinical outcomes of the Stem Cell Regenera study using G-CSF mobilization of peripheral blood stem cells and intraovarian injection of stem cell factor-enriched platelet rich plasma in real-world-practice.” DOI - https://doi.org/10.18632/aging.206274 Corresponding author - Amparo Santamaria - Amparo.santamaria@ivirma.com Video interview - https://www.youtube.com/watch?v=Zlezd0x_EJQ Longevity & Aging Series - www.aging-us.com/longevity Abstract The study assesses the effectiveness and safety of the Stem Cell Regenera Treatment for oocyte activation in women with ovarian failure, including conditions such as Poor Ovarian Response (POR), Diminished Ovarian Reserve (DOR), and Premature Ovarian Insufficiency (POI). This retrospective observational study was conducted from January 2023 to December 2024 at the IVIRMA Alicante Clinics in Spain. Women diagnosed with ovarian failure participated in the study, which involved mobilizing Hematopoietic Stem Cells from bone marrow into peripheral blood using granulocyte colony- stimulating factor (G-CSF). This was followed by an intraovarian injection of Stem Cell Factor- enriched Platelet Rich Plasma (SCFE-PRP). The primary outcome measures were the rate of oocyte activation, leukocytes and stem cell count, and pregnancy rates. Oocyte activation was defined as an increase in total Antral Follicle Count of three or more follicles after treatment and/or at least a 20% rise in Anti-Müllerian Hormone levels. Safety was assessed based on adverse effects. Pregnancy rates were evaluated for both spontaneous gestation and following in vitro fertilization (IVF) treatment. A total of 145 women participated: the overall activation rate was 68.28%, with 7.07% achieving spontaneous gestation and 14.14% achieving pregnancy following IVF. Mobilization of CD34+ cells was successful in all participants, with an average collection of 32.96 CD34+ cells/μl. No severe adverse effects were observed. The study concluded that the Stem Cell Regenera Treatment is effective and safe for oocyte activation in women with ovarian failure in real-world practice. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206274 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Stem Cell Regenera, oocyte activation, ovarian regeneration, G-CSF, SCFE-PRP, ovarian failure To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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 — November 13, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 3, 2025, titled “The role of phenylalanine and tyrosine in longevity: a cohort and Mendelian randomization study.” In this study led by Jie V. Zhao, Yitang Sun, Junmeng Zhang, and Kaixiong Ye from the University of Hong Kong and the University of Georgia, researchers investigated whether two amino acids, phenylalanine and tyrosine, affect how long people live (lifespan). The results suggest that higher levels of tyrosine are linked to shorter life expectancy in men, pointing to potential sex-specific approaches to promoting longevity. Phenylalanine and tyrosine are amino acids involved in metabolism and brain function. Both are found in protein-rich foods and dietary supplements, but their long-term effects on aging are not well understood. Tyrosine, in particular, is a building block of neurotransmitters such as dopamine, which regulate mood and cognitive function, making it a molecule of interest in aging research. The study analyzed data from more than 270,000 individuals in the UK Biobank. Using both observational and genetic methods, the researchers examined the associations between blood levels of phenylalanine and tyrosine with overall mortality and predicted lifespan. Although both amino acids were initially linked to higher mortality risk, only tyrosine showed a consistent and potentially causal association with reduced life expectancy in men. Genetic analyses estimated that elevated tyrosine levels could shorten men's lifespan by nearly one year. No significant effect was observed in women. These findings remained consistent even after adjusting for related factors, including the role of phenylalanine. This suggests that tyrosine may independently influence aging. The researchers also observed that men tend to have higher tyrosine levels than women, which could partly explain the gender gap in lifespan. “Phenylalanine showed no association with lifespan in either men or women after controlling for tyrosine.” The exact mechanisms behind this effect are still under investigation. However, tyrosine's involvement in insulin resistance and the production of stress-related neurotransmitters may be contributing factors. Insulin resistance is associated with many age-related diseases, and hormone-related pathways influenced by tyrosine may differ between men and women, potentially explaining the sex-specific outcomes. Although tyrosine is commonly marketed as a supplement for enhancing focus and mental performance, the study raises concerns about its long-term impact on lifespan. While the researchers did not directly study tyrosine supplementation, their findings suggest that people with high tyrosine levels may benefit from dietary adjustments. Strategies such as protein restriction could help reduce tyrosine levels and support healthier aging. Further studies are needed to confirm these findings and explore whether diet and lifestyle changes can safely lower tyrosine levels to promote longevity. DOI - https://doi.org/10.18632/aging.206326 Corresponding author - Jie V. Zhao - janezhao@hku.hk Abstract video - https://www.youtube.com/watch?v=rr0G44TD36M Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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-US proudly sponsored the Future of Aging Research (FAR) Mixer 2025, hosted by the Aging Initiative on November 7 in Cambridge, MA, uniting students, researchers, and biotechnology leaders to advance aging research and shape a healthier, longer-lived future. Highlights from the FAR Mixer 2025 The 2025 FAR Mixer featured keynote speaker Dr. Kristen Fortney, Co-Founder and CEO of BioAge Labs, who shared insights into how translational research and clinical pipelines have evolved over the past decade. Dr. Fortney highlighted how obesity-targeting drugs are opening new avenues for metabolic and aging research. She explained that while obesity and osteoporosis are currently major therapeutic priorities, the next wave of reimbursable diseases will likely focus on muscle loss and chronic inflammation, reflecting their growing recognition as key factors in healthy aging. She also emphasized the importance of human databases in target discovery, cross-sector partnerships between pharma and biotech, and the increasing focus on small-molecule interventions to address age-related diseases. Focus talks showcased the diversity and depth of modern aging research. Full recap - https://aging-us.org/2025/11/aging-us-supports-the-future-of-aging-research-mixer-2025/ To learn more about the journal, please visit 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/@Aging-US LinkedIn - www.linkedin.com/company/aging/ Bluesky - bsky.app/profile/aging-us.bsky.social Pinterest - www.pinterest.com/AgingUS/ Spotify - open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Synucleinopathies are a group of age-related neurological disorders, including Parkinson's disease, dementia with Lewy bodies, and multiple system atrophy. Most individuals are not diagnosed until these diseases have significantly progressed, as early symptoms, such as a reduced sense of smell, subtle cognitive or motor changes are too vague to serve as reliable indicators. To uncover specific biological signs that appear earlier and clearly point to the disease process, researchers from Saarland University developed a study titled “Brain region-specific and systemic transcriptomic alterations in a human alpha-synuclein overexpressing rat model,” featured as the cover Aging-US, Volume 17, Issue 10. Full blog - https://aging-us.org/2025/11/alpha-synuclein-overexpression-in-rats-reveals-early-clues-to-synucleinopathies/ Paper DOI - https://doi.org/10.18632/aging.206331 Corresponding author - Thomas Hentrich - thomas.hentrich@uni-saarland.de Abstract video - https://www.youtube.com/watch?v=Yl6AfVchkb0 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206331 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, alpha-synuclein, transgenic rat model, different brain regions, transcriptome analysis To learn more about the journal, please visit 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/@Aging-US 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 — November 11, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on October 1, 2025, titled “L-β-aminoisobutyric acid (L-BAIBA) in combination with voluntary wheel running exercise enhances musculoskeletal properties in middle-age male mice.” In this study led by first author Julian A. Vallejo and corresponding author Michael J. Wacker from the University of Missouri, Kansas City, researchers investigated how L-β-aminoisobutyric acid (L-BAIBA), a natural compound released during exercise, works together with regular physical activity to improve muscle and bone health in middle-aged male mice. The findings may support new strategies to maintain musculoskeletal health in aging populations, especially those at risk for mobility loss or osteoporosis. Muscle and bone strength naturally decline with age, increasing the risk of falls, fractures, and reduced quality of life. While exercise remains the most effective way to counteract this deterioration, it is often difficult for older individuals to maintain sufficient activity levels to see results. L-BAIBA, a molecule naturally produced during physical activity, is known to promote energy metabolism and support muscle and bone cells. This study explored its potential to work in synergy with endurance exercise to maximize health benefits in aging bodies. Researchers studied 12-month-old male mice that were split into different groups. Some remained sedentary, while others exercised freely on running wheels. Half of each group received daily L-BAIBA supplementation. After three months, the mice that received both the supplement and exercise showed greater improvements than those receiving either one alone. The soleus, a slow-twitch muscle essential for endurance and balance, grew larger and stronger only in the combined treatment group. These muscles also shifted to a more fatigue-resistant fiber type and had a larger number of oxidative fibers. “To investigate this hypothesis, we subjected 12-month-old (as a model of middle-age) male C57BL6 mice to voluntary wheel running (VWR) with L-BAIBA (100mg/kg/day) (VWR+L-BAIBA), VWR alone, L-BAIBA alone, or none (CTRL) for three months.” The study also showed significant improvements in bone health. Mice that received both exercise and L-BAIBA developed thicker and denser trabecular bone, along with reduced fat levels in the bone marrow, indicators of stronger, healthier bones. These changes were not observed in the groups that only exercised or only received L-BAIBA. Although the compound caused minor changes in heart electrical activity, it did not affect heart size or overall function, suggesting it is safe in this setting. These findings suggest that L-BAIBA may enhance the benefits of physical activity by supporting muscle strength and bone structure, particularly in slow-twitch muscle fibers. This combination could serve as a therapeutic strategy to help older adults, including those unable to engage in regular exercise, maintain musculoskeletal health. As the aging population grows, there is a growing need for solutions that support muscle and bone health without requiring strenuous activity. This research highlights the potential of natural, exercise-related molecules like L-BAIBA to help maintain mobility and strength throughout aging. DOI - https://doi.org/10.18632/aging.206325 Corresponding author - Michael J. Wacker — wackerm@umkc.edu Abstract video - https://www.youtube.com/watch?v=A-zfrLUikfQ Visit 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/@Aging-US 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 — November 5, 2025 — A new #research paper was #published in Volume 17, Issue 10 of Aging-US on September 10, 2025, titled “Longitudinal associations of epigenetic aging with cognitive aging in Hispanic/Latino adults from the Hispanic Community Health Study/Study of Latinos.” In this study led by Myriam Fornage, from The University of Texas Health Science Center at Houston, researchers found that faster biological aging, measured by DNA-based epigenetic clocks, is associated with greater cognitive decline and higher risk of mild cognitive impairment (MCI) in Hispanic/Latino adults. The results highlight the potential of epigenetic clocks to track changes in brain health over time, helping improve early detection and monitoring of age-related cognitive problems. Cognitive decline and dementia are major public health concerns, especially among aging populations. In this study, researchers followed 2671 Hispanic/Latino adults (average age 57; 66% women) over a seven-year period. They measured each participant's biological age using epigenetic clocks and assessed their cognitive performance at two time points. “We evaluated the associations of 5 epigenetic clocks and their between-visit change with multiple measures of cognitive aging that included a global and domain-specific cognitive function score at each visit, between-visit change in global and domain-specific cognitive function score, and MCI diagnosis at visit 2 (V2).” Epigenetic clocks estimate biological age based on DNA chemical modifications, called methylation, that accumulate with age. The study evaluated five different clocks, including newer models like GrimAge and DunedinPACE, which are designed to more accurately reflect health-related aging. The researchers found that individuals with faster biological aging showed lower cognitive function and higher probability of developing MCI over time. Among the five clocks studied, newer models such as GrimAge and DunedinPACE showed the strongest associations with memory, processing speed, and overall brain health. These findings suggest that tracking changes in biological age over time may be more effective than relying on a single measurement to identify those at risk for cognitive impairment. Importantly, the associations between biological aging and cognitive decline remained significant even after accounting for other known risk factors such as education, language preference, and cardiovascular health. This supports the idea that epigenetic clocks capture unique biological processes that influence brain aging. The study also found that the impact of changes in biological age over time was comparable to that of APOE4, a well-established genetic risk factor for Alzheimer's disease. Overall, this is the first large-scale study to examine these associations in a Hispanic/Latino population, a group that is underrepresented in aging research. By identifying early biological signs of brain aging, this work highlights the potential of epigenetic clocks as tools for routine health assessments. Monitoring changes in these biological markers could help detect individuals at risk for cognitive decline and guide timely interventions to preserve brain health. DOI - https://doi.org/10.18632/aging.206317 Corresponding author - Myriam Fornage - Myriam.Fornage@uth.tmc.edu Abstract video - https://www.youtube.com/watch?v=kG0Y-F_sods To learn more about the journal, please visit https://www.Aging-US.com​​ and connect with us on social media: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@Aging-US 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 — November 3, 2025 — A new #research paper featured on the #cover of Volume 17, Issue 10 of Aging-US was #published on October 20, 2025, titled “Brain region-specific and systemic transcriptomic alterations in a human alpha-synuclein overexpressing rat model.” In this study, led by first author Vivien Hoof and corresponding author Thomas Hentrich from Saarland University, Germany, researchers investigated how excess alpha-synuclein—a protein linked to Parkinson's disease—affects gene activity in different brain regions and the gut. They found that early, region-specific gene disruptions may contribute to the appearance of disease, with some effects also detected in the gut. These early molecular changes could serve as biomarkers for Parkinson's and point to new directions for treatment. Alpha-synuclein accumulates in the brains of individuals with Parkinson's disease and other age-related neurological conditions known as synucleinopathies. To better understand this process, the research team used a genetically modified rat model that overexpresses human alpha-synuclein. They studied gene expression in the striatum, cortex, and cerebellum—three key brain regions involved in movement and cognition—and analyzed how these changes evolved with age. “Transcriptomic analyses were performed on gene and transcript level of striatal, frontocortical, and cerebellar tissue in 5- and 12-month-old transgenic (BAC SNCA) and wild type rats […]” The results showed that gene alterations appeared earlier and were more pronounced in young rats, particularly in the striatum and cortex, before any visible signs of disease manifested. This early disruption challenges the common belief that gene alterations gradually increase with age and suggests that early-life molecular changes may be critical in disease development. The researchers also found that many gene expression changes were unique to individual brain regions. However, they identified a set of genes that were consistently affected across all brain regions and the gut. This suggests that the disease may begin to affect the entire body—not just the brain—long before symptoms become noticeable. Several of the shared genes are involved in synaptic signaling and inflammation—processes known to be altered in Parkinson's. Others are linked to dopamine production and neuronal plasticity, indicating potential early efforts by the brain to compensate for the harmful effects of the alpha-synuclein buildup. Overall, this study provides a detailed view of how alpha-synuclein affects gene networks early in the disease process. Understanding these changes may help identify biomarkers and develop targeted therapies before irreversible brain damage occurs. DOI - https://doi.org/10.18632/aging.206331 Corresponding author - Thomas Hentrich - thomas.hentrich@uni-saarland.de Abstract video - https://www.youtube.com/watch?v=Yl6AfVchkb0 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206331 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, alpha-synuclein, transgenic rat model, different brain regions, transcriptome analysis To learn more about the journal, please visit 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/@Aging-US 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 — October 27, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 17, 2025, titled “Depletion of the TRF1 telomere-binding protein leads to leaner mice with altered metabolic profiles.” In this study led by first author Jessica Louzame Ruano and corresponding author Maria A. Blasco from the Spanish National Cancer Centre (CNIO), researchers investigated the role of TRF1, a protein known for protecting telomeres, in regulating whole-body metabolism. The results suggest that TRF1 influences metabolic health through mechanisms unrelated to its known function in telomere maintenance. Obesity and metabolic disorders are major health concerns, especially as people age. To explore TRF1's role beyond telomere protection, the research team studied both normal mice and genetically modified mice that lacked TRF1. Mice without TRF1 remained leaner over time, resisted fat accumulation, and showed healthier blood sugar and insulin levels compared to normal mice. Importantly, these benefits occurred without any detectable shortening of telomeres. The leaner body composition in TRF1-deficient mice was not due to reduced food intake or increased physical activity. Instead, the fat loss appeared to result from biological changes in how energy was processed and stored. Male mice without TRF1 gained less weight and had lower LDL cholesterol levels, even on a high-fat diet. Female mice showed milder effects, reflecting known sex-based differences in susceptibility to diet-induced obesity. This highlights the importance of including both sexes in metabolic research. “Major metabolic pathways related with energy production and regulation of metabolism homeostasis were also found downregulated in Trf1-deficient mice.” Gene expression analysis in the liver revealed shifts in several key pathways. Genes related to fat production, energy generation, and muscle growth were downregulated, while genes linked to inflammation and cholesterol synthesis were upregulated. The mice also showed signs of higher energy expenditure and a shift from using fat to protein as an energy source, possibly due to their reduced fat reserves. However, some older mice developed mild liver stress, including fibrosis and DNA damage, suggesting a possible long-term trade-off. Overall, this study expands the understanding of how telomere-related proteins influence more than just cellular aging. By identifying a connection between TRF1 and metabolism, the research opens new possibilities for targeting TRF1 or its pathways to address obesity and related conditions. Still, further studies are needed to clarify how TRF1 affects fat development and whether similar effects occur in humans. DOI - https://doi.org/10.18632/aging.206320 Corresponding author - Maria A. Blasco — mblasco@cnio.es Abstract video - https://www.youtube.com/watch?v=7AG3TBgDZIw Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206320 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Trf1, metabolism, leaner, fat, telomeres To learn more about the journal, visit 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 — October 23, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 11, 2025, titled “Roles of plasminogen activator inhibitor-1 in aging-related muscle and bone loss in mice.” In this study led by first author Takashi Ohira and corresponding author Hiroshi Kaji from Kindai University Faculty of Medicine, researchers found that female mice lacking the gene for plasminogen activator inhibitor-1 (PAI-1) were protected from age-related muscle weakness and bone thinning. This suggests that PAI-1 could be a potential target for future treatments to reduce frailty in aging populations. As the global population continues to age, more people are affected by conditions such as sarcopenia and osteoporosis. These disorders involve the progressive loss of skeletal muscle mass and bone density, leading to reduced mobility, a greater risk of falls, and a lower quality of life. To investigate the role of PAI-1 in aging, researchers compared young (6-month-old) and aged (24-month-old) male and female mice, with and without the PAI-1 gene. They found that PAI-1 levels increased with age in both sexes. However, only female mice lacking the PAI-1 gene experienced a significant reduction in age-related muscle and bone loss. Female mice without PAI-1 maintained stronger grip strength and greater muscle mass in their lower limbs. They also showed less cortical bone loss in their femurs and tibias. In contrast, male mice did not experience the same benefits, despite also showing increased levels of PAI-1 with age. These results suggest that PAI-1 contributes to aging-related decline in a sex-specific manner. “The present study found that lower limb muscle mass, gastrocnemius and soleus muscle tissue weights, and grip strength were significantly lower in 24-month-old male and female wild-type mice than in their 6-month-old counterparts.” PAI-1 plays key roles in blood clotting, inflammation, and cellular senescence—a process in which aging cells release harmful molecules that affect nearby tissues. One of these molecules, interleukin-6 (IL-6), is a major driver of inflammation. The researchers found that aged female mice lacking PAI-1 had lower IL-6 levels in both muscle and blood, suggesting that PAI-1 may contribute to muscle and bone loss by promoting inflammation. These protective effects were also not associated with changes in muscle protein turnover or reductions in fibrous tissue, reinforcing the idea that PAI-1's impact is likely driven by inflammatory signaling. This study highlights PAI-1 as a promising therapeutic target for slowing or preventing age-related declines in muscle and bone health, particularly in women. Since postmenopausal women are especially vulnerable to osteoporosis and frailty, a better understanding of how PAI-1 contributes to aging could lead to new strategies for maintaining strength and mobility in later life. Further research is needed to explore how PAI-1 interacts with other age-related biological changes and why its effects differ between sexes. DOI - https://doi.org/10.18632/aging.206318 Corresponding author - Hiroshi Kaji - hkaji@med.kindai.ac.jp Abstract video - https://www.youtube.com/watch?v=hg4qKf-oO2I Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts To learn more about the journal, please visit 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/@Aging-US 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 — October 21, 2025 — A new #editorial was #published in Aging-US on October 13, 2025, titled “Longevity clinics: between promise and peril.” In this editorial, Marco Demaria, Editor-in-Chief of Aging-US, from the European Research Institute for the Biology of Ageing (ERIBA), University Medical Center Groningen (UMCG), University of Groningen (RUG), reviews the rapid rise of longevity clinics worldwide. Longevity clinics have emerged globally in response to increasing demand for personalized, preventive healthcare. Located in countries such as the United States, Switzerland, and the United Arab Emirates, these centers offer advanced diagnostic services, including genomic testing, advanced imaging, and multi-omics profiling. Their goal is to extend healthspan—the number of years a person lives in good health—through customized lifestyle interventions, nutritional guidance, and, in some cases, experimental therapies. “Longevity clinics embody an important vision: healthcare is personalized, preventive, and engaged.” Although the concept of proactive aging care is attractive, the editorial raises serious concerns about the scientific and ethical foundations of these clinics. Many operate outside conventional medical systems and lack connections to academic geroscience. This disconnection allows them to market expensive interventions without sufficient clinical validation. Program costs can range from €10,000 to over €100,000 per year, limiting access to wealthy individuals while leaving out populations most at risk for premature aging. Despite these challenges, Dr. Demaria notes that longevity clinics may contribute meaningfully to innovation. By collecting extensive, long-term health data from clients, these clinics have the potential to identify early biomarkers of aging and detect signs of age-related diseases. Unlike traditional clinical trials, which are limited in scope and duration, longevity clinics track a wide range of health data over time. When paired with artificial intelligence tools, this information could help advance the science of healthy aging. However, several risks remain. Many clinics lack standardized protocols, and the tools they use, such as biological age calculators or hormone therapies, often lack accuracy or clear clinical value. Without proper guidelines, clients may receive advice that is confusing or not scientifically supported. This can reduce public trust in the broader field of longevity research. To ensure these clinics contribute positively to health innovation, the editorial outlines different key steps: greater collaboration with academic researchers, the adoption of standardized protocols, increased transparency, and work toward regulatory clarity. Broader access must also be considered by developing scalable and more affordable models, possibly through partnerships with public health systems. Ultimately, longevity clinics represent both a major opportunity and a serious concern. If integrated responsibly with science, policy, and public health, they could support a shift toward personalized, preventive healthcare. Without this alignment, however, they risk reinforcing inequality and weakening the credibility of the science behind aging. DOI - https://doi.org/10.18632/aging.206330 Corresponding author - Marco Demaria — m.demaria@umcg.nl Abstract video - https://www.youtube.com/watch?v=Bt84xBdii0s To learn more about the journal, visit 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 — October 17, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on September 8, 2025, titled, “Runx1 overexpression induces early onset of intervertebral disc degeneration.” In this study, led by first author Takanori Fukunaga from Emory University School of Medicine and corresponding author Hicham Drissi from Emory and the Atlanta VA Medical Center, researchers found that the Runx1 gene, when overactive in spinal disc cells, can accelerate age-related degeneration of the intervertebral discs. The findings offer new insight into the genetic factors that drive disc aging and suggest possible directions for treating chronic back pain. Intervertebral discs cushion the spine and support movement. Their deterioration is a major cause of lower back pain, especially with aging. At the center of each disc is the nucleus pulposus (NP), a gel-like core that contains proteins such as collagen and aggrecan, which help retain water and maintain structure. As people age, NP cells often lose their function, contributing to disc breakdown. Using a genetically modified mouse model, the researchers activated Runx1 specifically in NP cells. These mice developed signs of disc degeneration by five months of age, which is much earlier than normal. The overexpression of Runx1 led to the loss of healthy NP cells, an increase in abnormal cell types, and damage to disc structure. Levels of essential proteins like aggrecan and type II collagen decreased, while type X collagen increased, signaling unhealthy tissue changes. “To achieve NP-specific postnatal overexpression of Runx1, we crossed Krt19CreERT mice with Rosa26-Runx1 transgenic mice previously generated in our laboratory.” A key finding was that Runx1 overactivity did not kill cells directly. Instead, it caused premature cellular aging, known as senescence. Senescent cells lose the ability to repair tissue, creating an environment that accelerates degeneration. Markers of senescence were significantly elevated in the affected discs. The researchers also observed a dose-dependent response. The more Runx1 was activated, the more severe the degeneration was. This suggests that targeting Runx1 may be a promising strategy to prevent or slow disc aging. Overall, this study highlights the genetic and cellular processes that contribute to intervertebral disc degeneration, a leading cause of disability. By identifying Runx1 as a potential driver of early disc aging, the research opens new opportunities for intervention and treatment of degenerative spine conditions. DOI - https://doi.org/10.18632/aging.206316 Corresponding author - Hicham Drissi - hicham.drissi@emory.edu Abstract video - https://www.youtube.com/watch?v=BPwWbVBPIUM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206316 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - cell senescence, aging, Runx1, nucleus pulposus, intervertebral disc degeneration 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/@Aging-US 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 people age, it is common to experience some memory lapses or slower thinking. Although this is often a normal part of aging, it can still affect a person's quality of life. Scientists have been investigating ways to slow or prevent cognitive decline, and growing evidence points to the potential role of social interaction. Recently, a study using rats found that long-term social connection may help protect the brain from age-related memory decline. This work, titled “The impact of long-term social housing on biconditional association task performance and neuron ensembles in the anterior cingulate cortex and the hippocampal CA3 region of aged rats,” was recently published in Aging-US (Volume 17, Issue 9). Full blog - https://aging-us.org/2025/10/how-long-term-social-connection-supports-brain-health-and-memory-in-aging/ Paper DOI - https://doi.org/10.18632/aging.206310 Corresponding author - Anne M. Dankert - adankert@unc.edu Abstract video - https://www.youtube.com/watch?v=poNnPz1ti6Q Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206310 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, aging, environmental enrichment, working memory, complex cognition, immediate early genes 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 — October 14, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 30, 2025, titled, “Glycocalyx-targeted therapy prevents age-related muscle loss and declines in maximal exercise capacity.” In this study, led by Daniel R. Machin from the University of New Mexico School of Medicine and the University of Utah, researchers found that protecting a fragile layer lining blood vessels, known as the glycocalyx, can prevent muscle deterioration and help maintain physical performance during aging. They also discovered that a supplement containing high-molecular-weight hyaluronan (HMW-HA), a key component of the glycocalyx, enabled older mice to preserve muscle mass and exercise capacity. These findings suggest that targeting the glycocalyx may offer a new approach to reduce frailty and support mobility in older adults. As this layer degrades with age, it contributes to cardiovascular and muscular decline by impairing blood flow and vascular health. The study examined how preserving the glycocalyx using a therapy called Endocalyx™ affects physical function in aging mice. Researchers first studied genetically modified mice lacking Has2, the enzyme responsible for producing HMW-HA. These mice had a thinner glycocalyx, reduced exercise performance, and lower mitochondrial function in their muscles, even though muscle size remained normal. This indicated that glycocalyx damage alone can directly impair physical performance. The team then gave older mice a diet containing Endocalyx™ for 10 weeks. Compared to untreated controls, these mice maintained muscle mass and performed better on treadmill tests. Notably, the treated mice did not show the typical age-related decline in muscle strength and endurance. While the supplement did not fully restore youthful performance, it significantly slowed physical deterioration, suggesting a protective benefit. In contrast, untreated older mice lost both body mass and muscle volume during the same period. “Taken together, these findings provide direct evidence of a role for HMW-HA in the modulation of exercise capacity.” This research builds on prior evidence that the glycocalyx is essential for healthy blood vessel function. Since muscle health depends on proper blood flow and oxygen delivery, restoring the glycocalyx may help maintain strength and mobility with age. While more research is needed to confirm these results in humans, the findings point to a potential therapeutic approach to promote healthier aging. DOI - https://doi.org/10.18632/aging.206313 Corresponding author - Daniel R. Machin — dmachin@salud.unm.edu Abstract video - https://www.youtube.com/watch?v=S7HjCeXT8fU Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206313 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, glycocalyx, hyaluronan 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

Federica Grosso from the Institute for Genetic and Biomedical Research (IRGB) of the National Research Council (CNR) in Monserrato, Italy, describes a #research paper she co-authored that was #published in Volume 17, Issue 8 of Aging-US, entitled “Causal relationships between gut microbiome and hundreds of age-related traits: evidence of a replicable effect on ApoM protein levels.” DOI - https://doi.org/10.18632/aging.206293 Corresponding author - Serena Sanna - serena.sanna@cnr.it Video interview - https://www.youtube.com/watch?v=qYg42_gn_pw Abstract In the past 20 years, the involvement of gut microbiome in human health has received particular attention, but its contribution to age-related diseases remains unclear. To address this, we performed a comprehensive two-sample Mendelian Randomization investigation, testing 55130 potential causal relationships between 37 traits representing gut microbiome composition and function and age-related phenotypes, including 1472 inflammatory and cardiometabolic circulating plasma proteins from UK Biobank Pharma Proteomic Project and 18 complex traits. A total of 91 causal relationships remained significant after multiple testing correction (false discovery rate p-value

BUFFALO, NY — October 9, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 22, 2025, titled, “The impact of long-term social housing on biconditional association task performance and neuron ensembles in the anterior cingulate cortex and the hippocampal CA3 region of aged rats.” The research team led by Anne M. Dankert from Providence College and University of North Carolina, Chapel Hill, showed that aged rats who lived in socially enriched environments throughout life retained better memory and cognitive flexibility than those housed alone. This study highlights the importance of social interaction in protecting the aging brain. Cognitive decline, such as memory loss and reduced problem-solving ability, affects many people over the age of 65. While many factors contribute to age-related cognitive decline, this study suggests that one key factor may be surprisingly simple: long-term social connection. To explore how social interaction might influence memory performance and brain activity, the researchers designed a study using rats as a model for aging in humans. “Cognitive decline and changes in neuronal activity are hallmarks of aging.” They compared three groups of rats: young adults, aged rats housed alone, and aged rats housed socially in groups. All groups had access to the same physical enrichment, such as exercise and stimulating objects, but only some experienced lifelong social companionship. The team tested these animals on a complex memory challenge known as the biconditional association task, which requires animals to make context-based decisions—an ability that typically declines with age. The results showed that aged rats living in social groups performed just as well as young adults on the memory task, while those housed alone showed significant impairments. Socially housed rats also made fewer working memory errors and required less effort to complete cognitive tasks, suggesting not only better performance but more efficient brain function. These benefits were not observed in aged rats who received only environmental enrichment without social interaction. Brain imaging revealed additional differences between the groups. Socially housed aged rats showed increased activity in the hippocampus, particularly in the CA3 region, which plays a key role in forming and separating memories. In contrast, aged rats that lived alone had lower activity in this region, which may explain their poorer performance. Interestingly, socially housed rats also showed reduced overactivity in the anterior cingulate cortex—a brain area involved in attention and decision-making—suggesting a more balanced and efficient neural response. This research provides new insight into how lifelong social experiences shape brain health during aging. While earlier studies have shown that physical activity and cognitive stimulation help preserve cognitive function, this study identifies social interaction as an independent and powerful protective factor. The findings are consistent with human studies showing that older adults who remain socially active tend to experience slower cognitive decline and stronger brain function. Overall, these results emphasize that brain aging is not inevitable but may be influenced by our social environments. This research suggests that fostering lifelong social connections could be a critical, low-cost strategy to protect memory and mental flexibility in older adults. DOI - https://doi.org/10.18632/aging.206310 Corresponding author - Anne M. Dankert - adankert@unc.edu Abstract video - https://www.youtube.com/watch?v=poNnPz1ti6Q https://www.aging-us.com/ MEDIA@IMPACTJOURNALS.COM