Aging-US

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 <0.05) and sensitivity analyses, notably two with the risk of developing age-related macular degeneration and 89 with plasma proteins. The link between purine nucleotides degradation II aerobic pathway and apolipoprotein M was further replicated using independent genome-wide association study data. Finally, by taking advantage of previously reported biological function of Faecalibacterium prausnitzii we found evidence of regulation of six proteins by its function as mucosal-A antigen utilization. These results support the role of gut microbiome as modulator of the inflammatory and cardiometabolic circuits, that may contribute to the onset of age-related diseases, albeit future studies are needed to investigate the underlying biological mechanisms. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206293 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, causal inference, aging, gut microbiome, inflammatory proteins, age-related macular 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/@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 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

Dr. Leonard Egede, Dr. Rebekah Walker, and Dr. Obinna Ekwunife from the Department of Medicine at the University of Buffalo, NY, describe their #research paper #published in Volume 17, Issue 8 of Aging-US, entitled “Longitudinal relationship between social and CVD risk factors in older adults with prediabetes: the HRS 2006-2016.” #interview #authorinterview #aging #prediabetes #cardiovascular #health #openaccess #openscience #peerreviewed #journal #publication #publishing #meded DOI - https://doi.org/10.18632/aging.206308 Corresponding author - Leonard E. Egede - legede@buffalo.edu Video interview - https://www.youtube.com/watch?v=1MSTk3GQAGA Video transcript - https://aging-us.net/2025/10/08/behind-the-study-social-and-cardiovascular-risk-factors-in-older-adults-with-prediabetes/ Abstract Background: This study examines how multiple social risk factors influence cardiovascular disease (CVD) risk control over time in older adults with prediabetes using a nationally representative cohort. Methods: Data from the Health and Retirement Study (HRS) included 5,086 U.S. adults aged 50+ with prediabetes. Five social risk domains (economic stability, environment, education, healthcare, and social context) were examined as independent variables, while CVD risk factors included glycemic control (HbA1c), systolic blood pressure (SBP), and cholesterol ratio (total cholesterol/high-density lipoprotein). Mixed-effects models assessed relationships between social risk factors and CVD outcomes, adjusting for age, gender, race, and marital status. Results: The sample had an average age of 68.6 years, with 60.2% female, and 70.97% identifying as non-Hispanic Black. Average HbA1c was 5.7, SBP 129.4, and cholesterol ratio 3.85. Limited education was consistently associated with increased CVD risk—HbA1c (β = 0.03, 95% CI: 0.01–0.06, p < 0.001), SBP (β = 4.34, 95% CI: 2.96–5.71, p < 0.001), and cholesterol ratio (β = 0.08, 95% CI: 0.01–0.16, p < 0.05) —in the fully adjusted model. Medication cost-related non-adherence was significantly associated with higher HbA1c levels (β = 0.03, 95% CI: 0.002–0.06, p < 0.05). Difficulty paying bills and lack of health insurance were both significantly associated with higher cholesterol levels (β = 0.03, 95% CI: 0.002–0.06, p < 0.05) and (β = 0.22, 95% CI: 0.15–0.30, p < 0.001), respectively. Conclusions: Social risk factors, particularly limited education, significantly impact CVD risk in older adults with prediabetes. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206308 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, prediabetes, social determinants of health, health equity, cardiovascular health, population health 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 7, 2025 — A new #research paper was #published in Volume 17, Issue 9 of Aging-US on August 27, 2025, titled, “Deregulated miR-145 and miR-27b in Hutchinson-Gilford progeria syndrome: implications for adipogenesis.” In this study, led by first author Felix Quirin Fenzl and corresponding author Karima Djabali from the Technical University of Munich (TUM), researchers identified that miR-145-5p and miR-27b-3p interfere with the formation of fat cells in children with Hutchinson-Gilford progeria syndrome (HGPS), a rare and fatal premature aging disorder. Their findings help explain why patients often experience fat loss and related metabolic complications and suggest new potential therapeutic strategies. Hutchinson-Gilford progeria syndrome is a genetic condition that causes rapid aging in children, often leading to early death due to heart disease. Although affected children appear healthy at birth, they soon develop signs of accelerated aging, including hair loss, stiff joints, and a significant reduction in fat tissue. While certain treatments can slow disease progression, many aspects, such as the loss of fat tissue, remain poorly understood. “Overall, this study provides the first comprehensive miRNA profiling of HGPS and control fibroblasts across different stages of cellular senescence.” This study focused on how microRNAs—tiny molecules that help regulate gene expression—contribute to the disease. To explore this, the researchers used skin-derived stem cells from both healthy individuals and HGPS patients. When they transformed these cells into fat cells, the HGPS-derived stem cells formed significantly fewer fat cells. This difference was linked to unusually high levels of miR-145-5p and miR-27b-3p. These molecules were found to silence important genes required for fat cell growth and function. When the researchers blocked these microRNAs, fat cell formation improved. The team also examined fat tissue from a mouse model of HGPS. Similar to the human cells, these mice showed increased levels of miR-145-5p and miR-27b-3p and impaired fat development. These results confirm that these two microRNAs play a central role in the loss of fat tissue seen in the disease. Importantly, reducing their activity could become a promising therapeutic strategy for restoring fat tissue in affected individuals. Although further research is needed before developing treatments, this study represents a step forward in understanding the molecular causes of lipodystrophy, a condition in which the body cannot form healthy fat tissue, in HGPS. It also opens the door for future therapies that could improve quality of life and health outcomes for patients. In the long term, similar approaches might benefit people with other metabolic diseases, such as obesity or diabetes, where fat cell function is also disrupted. DOI - https://doi.org/10.18632/aging.206309 Corresponding authors - Karima Djabali — djabali@tum.de Abstract video - https://www.youtube.com/watch?v=b0ksC3cvdZ0 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206309 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Hutchinson-Gilford progeria syndrome (HGPS), progerin, microRNAs, adipogenesis 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 3, 2025 — A new #research perspective was #published in Volume 17, Issue 9 of Aging-US on August 26, 2025, titled “Analysis of the current state of frailty indexes and their implementation for aging intervention studies.” In this work, led by first author Oliver G. Frost from Loughborough University alongside corresponding authors Abdelhadi Rebbaa and Amit Sharma, from the Lifespan Research Institute, the authors explore growing concerns about the lack of standardization in how frailty is measured in rodent aging studies, which may limit the development of effective interventions targeting age-related decline. Frailty, a key indicator of deteriorating health in older adults, is increasingly assessed in preclinical models using frailty indexes (FIs). These indexes quantify health deficits, such as reduced mobility, cognitive decline, or physical weakness. However, this perspective highlights that FI methodologies vary significantly across studies, from the selection of parameters to the cut-off thresholds used, resulting in inconsistent outcomes that affects reproducibility and translational value. The authors reviewed 18 rodent studies and found substantial variation in how frailty is defined and measured. Some FIs rely on clinical observations, such as appearance or beahaviour, while others focus on physical performance metrics like grip strength or locomotion. In several cases, applying different FIs to the same group of animals produced contradictory results, underscoring the importance of harmonized protocols. To illustrate these issues, the researchers applied an 8-item FI to mice of different ages and found that even young mice were sometimes scored as frail, depending on the scoring method and reference values. This finding emphasizes the need for consistent baselines and controlled environments, especially when comparing across studies. The authors recommend using each animal as its own baseline in longitudinal studies, a strategy that enhances reliability without adding significant cost. “Sex as a biological variable in FIs is an important consideration, as there is a known difference between male and female frailty onset and progression.” The authors also discuss emerging automated tools, such as video-based open-field testing, which can reduce observer bias and improve reproducibility. In the future, broader health indicators, such as cognition, circadian rhythms, social behavior, and body composition, may further enhance frailty assessments. Overall, this work underscores the urgent need for standardized, transparent, and reproducible methods for evaluating frailty in preclinical aging studies. Improved consistency in frailty scoring will better inform the development of healthspan-extending therapies and enhance the translational relevance of animal models. DOI - https://doi.org/10.18632/aging.206307 Corresponding authors - Abdelhadi Rebbaa - rebbaa@gmail.com, and Amit Sharma - amit.sharma@sens.org Abstract video - https://www.youtube.com/watch?v=eha3XA9LyWA Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206307 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, frailty, rodents, frailty index, phenotype To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us on social media at: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

As life expectancy increases, there is growing interest not only in extending lifespan but also in improving the quality of those additional years. To address the physical and cognitive decline that often accompanies aging, researchers have explored a variety of strategies. Many of these focus on a single biological factor, such as reducing inflammation or stimulating stem cell activity. However, aging is a complex process involving multiple, interconnected changes in the body. Recognizing this, researchers at the University of California, Berkeley proposed a more comprehensive approach: targeting multiple aging-related pathways simultaneously. Their study, titled “Sex-specific longitudinal reversal of aging in old frail mice,” was recently featured on the cover of Aging-US (Volume 17, Issue 9). Full blog - https://aging-us.org/2025/10/new-anti-aging-combo-boosts-lifespan-in-old-male-mice/ Paper DOI - https://doi.org/10.18632/aging.206304 Corresponding author - Irina M. Conboy - irina@generationlab.co Abstract video - https://www.youtube.com/watch?v=bpWxDd7hHhM Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206304 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, lifespan, healthspan, Alk5 inhibitor, oxytocin, sex-specific differences To learn more about the journal, please visit our website at https://www.Aging-US.com​​ and connect with us: Facebook - https://www.facebook.com/AgingUS/ X - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Bluesky - https://bsky.app/profile/aging-us.bsky.social Pinterest - https://www.pinterest.com/AgingUS/ Spotify - https://open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

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

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

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

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

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

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

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

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

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

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