Aging-US

BUFFALO, NY — May 20, 2026 — A new #editorial was #published in Volume 18 of Aging-US on May 18, 2026, titled “Public health in the age of longevity interventions: from prevention to system-wide resilience.” The editorial was authored by Jochen Mierau from the University of Groningen and Aging-US Editor-in-Chief Marco Demaria from the University of Groningen and European Research Institute for the Biology of Ageing (ERIBA). In this editorial, the authors examine how modern public health systems may need to evolve as aging populations increasingly face chronic disease, frailty, multimorbidity, and progressive loss of function rather than the acute infectious diseases that shaped 20th-century medicine. The authors argue that many of the greatest gains in human lifespan historically came not from advanced medical technologies, but from broad public health interventions such as sanitation, vaccination, improved nutrition, occupational safety, safer housing, and access to education. While these measures remain essential, they suggest that modern aging societies now face a different challenge: extending healthspan alongside lifespan. The editorial highlights how today's health risks accumulate gradually across the life course through environmental, metabolic, social, and behavioral exposures. Ultra-processed foods, pollution, tobacco, alcohol, sedentary lifestyles, climate-related stressors, and social isolation are described as contributors to accelerated biological aging and increased vulnerability to chronic disease. The authors emphasize that these interconnected exposures cannot be fully addressed through disease-specific treatment alone. “Rather than representing separate or competing domains, these approaches should be viewed as complementary components of a unified strategy to improve population health across aging societies.” A major focus of the article is the growing scientific interest in longevity-directed interventions that target core biological mechanisms of aging. The authors discuss pathways including cellular senescence, chronic inflammation, metabolic dysfunction, and impaired proteostasis, noting that interventions directed at these processes may help delay or modify multiple age-related diseases simultaneously rather than treating each condition individually after it emerges. Importantly, the editorial emphasizes that longevity interventions should not replace either public health or conventional clinical medicine. Instead, the authors propose a coordinated framework operating across the life course. In this model, public health strategies reduce baseline risk and environmental damage, clinical medicine treats established disease, and longevity-focused therapies may help slow biological decline before major pathology becomes clinically apparent. Figure 1 of the paper (page 2) illustrates this proposed multi-layered framework integrating public health, longevity interventions, and disease-specific care across different stages of life. Full press release - https://www.aging-us.com/news-room/extending-healthspan-through-public-health-and-longevity-medicine DOI - https://doi.org/10.18632/aging.206381 Corresponding author - Marco Demaria - m.demaria@umcg.nl Paper Preview Video - https://www.youtube.com/watch?v=KSjfmxpHer8 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 — May 19, 2026 — A new #research paper was #published in Volume 18 of Aging-US on May 5, 2026, titled “Methylene blue protects hair follicle stem cells from oxidative and metabolic stress to enhance hair regeneration.” The study was led by first author Kavitha Sadashivaiah and corresponding author Kan Cao from the Department of Cell Biology and Molecular Genetics at the University of Maryland, College Park. In this study, the authors investigated how methylene blue (MB), a long-established mitochondrial-targeted antioxidant, affects human hair follicle stem cells (HFSCs) under conditions of oxidative and metabolic stress. Hair follicle stem cells are essential for maintaining hair growth and regeneration, but aging, ultraviolet radiation, oxidative stress, and metabolic dysfunction can impair their regenerative capacity and contribute to hair thinning and scalp aging. Using cultured human HFSCs, the researchers found that methylene blue significantly enhanced stem cell proliferation and viability while reducing intracellular reactive oxygen species (ROS). Importantly, MB also increased activation of β-catenin signaling, a central pathway involved in hair follicle regeneration, stem cell maintenance, and wound repair. Functional scratch-assay experiments further demonstrated that MB accelerated wound closure and regenerative activity in HFSC cultures. The study also explored how methylene blue interacts with other compounds commonly associated with scalp or hair health. While antioxidant vitamins A and C improved oxidative stress scavenging, they unexpectedly reduced MB-induced β-catenin activation when used in combination. In contrast, minoxidil—the widely used hair growth stimulant—worked synergistically with MB to further enhance β-catenin signaling and improve HFSC viability. “Overall, these findings identify methylene blue as a multifunctional therapeutic candidate that reduces oxidative and metabolic stress while supporting HFSC–mediated hair regeneration.” Another major focus of the paper involved glucagon-like peptide-1 receptor agonists (GLP-1 RAs), medications increasingly used for diabetes and weight management. Recent clinical observations have suggested that some patients receiving GLP-1 RA therapy may experience hair thinning or hair loss. The authors demonstrated that increasing GLP-1 RA concentrations caused dose-dependent reductions in HFSC viability in vitro. However, pretreatment with methylene blue substantially protected the stem cells from GLP-1 RA–associated metabolic stress and premature cell death. Beyond stem cell protection, the paper discusses methylene blue's broader potential role in scalp health. Because MB absorbs ultraviolet radiation and has previously demonstrated protective effects against UV-induced DNA damage in skin cells, the authors propose that it may help shield the scalp microenvironment from oxidative injury while supporting regenerative signaling pathways important for hair maintenance. The study also highlights MB's possible antimicrobial properties and its potential influence on scalp microbiome balance. Importantly, the authors emphasize that the findings are based on in vitro cellular models and that further in vivo studies will be necessary before clinical applications can be established. Additional research will be required to define appropriate dosing, pharmacokinetics, long-term safety, and therapeutic efficacy in living systems. Overall, this study identifies methylene blue as a potentially multifunctional therapeutic candidate for supporting hair follicle stem cell health under conditions of oxidative, metabolic, and pharmacologic stress. By combining antioxidant activity with activation of regenerative β-catenin signaling, MB may represent a promising future strategy for protecting scalp health, enhancing hair regeneration, and improving the resilience of aging hair follicle stem cells. DOI - https://doi.org/10.18632/aging.206376

Each month, we will highlight a paper published in Aging-US chosen as the “Editors' Choice.” These selections are handpicked by our editors and accompanied by a brief summary, showcasing research with significant impact and novel insights in aging and age-related diseases. __________ In the research paper, titled “Association of epigenetic age acceleration with MRI biomarkers of aging and Alzheimer's disease neurodegeneration,” researchers investigated whether epigenetic clocks of biological aging are associated with MRI markers of brain aging and Alzheimer's disease-related neurodegeneration in 1,196 older women. While none of the five epigenetic clocks examined were linked to accelerated overall brain aging, one measure (AgeAccelGrim2) was associated with MRI patterns related to neurodegeneration. The findings suggest this relationship was largely driven by DNA methylation markers linked to smoking history and changes in frontal and temporal brain regions rather than areas typically affected early in Alzheimer's disease. Overall, the study indicates that epigenetic aging and brain aging may reflect different aspects of the aging process, while highlighting the potential role of smoking-related biological aging in increasing dementia risk. DOI - https://doi.org/10.18632/aging.206369 Corresponding author - Linda K. McEvoy - linda.k.mcevoy@kp.org Abstract video - https://www.youtube.com/watch?v=kZiRjlKnnsI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206369 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenetic clocks, brain age, biological aging, smoking, frontal lobe 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 — May 15, 2026 — A new #review was #published in Volume 18 of Aging-US on May 4, 2026, titled “Cellular senescence: from pathogenic mechanisms to precision anti-aging interventions.” The study was led by first author Jian Deng and corresponding author Dong Yang from the Department of Targeting Therapy and Immunology, Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China. In this comprehensive review, the authors examine how cellular senescence contributes to aging and age-related disease across multiple organ systems, while also highlighting the emerging complexity and functional diversity of senescent cell populations. Traditionally, senescent cells have been viewed primarily as harmful byproducts of aging, characterized by irreversible cell-cycle arrest and chronic inflammatory signaling. However, growing evidence suggests that some senescent cells also play beneficial physiological roles in tissue repair, embryonic development, and maintenance of tissue homeostasis. The review outlines how senescence develops in major tissues including the liver, lungs, kidneys, heart, adipose tissue, brain, and skin. Across these organs, aging-related cellular dysfunction is driven by a combination of oxidative stress, mitochondrial dysfunction, DNA damage, chronic inflammation, metabolic stress, telomere shortening, and environmental insults such as ultraviolet radiation and pollution. The authors describe how senescent cells accumulate in highly specialized cell populations—including hepatocytes, endothelial cells, fibroblasts, macrophages, astrocytes, and epithelial cells—where they can disrupt normal tissue architecture and promote chronic disease progression. Importantly, the article emphasizes that senescent cells are highly heterogeneous and should not be treated as a uniform population. Depending on the tissue context and biological environment, senescent cells may exert either protective or harmful effects. For example, certain senescent cells may help limit fibrosis or support wound healing, whereas others drive chronic inflammation, metabolic dysfunction, tissue degeneration, and cancer progression. This growing recognition of functional heterogeneity has prompted a major shift in anti-aging research away from indiscriminate elimination of senescent cells toward more selective and precision-based therapeutic strategies. “Based on these insights, this review summarizes the induction mechanisms of cellular senescence and the subsequent evolution of their functional phenotypes across diverse tissues.” Full press release - https://www.aging-us.com/news-room/precision-anti-aging-strategies-aim-to-target-harmful-senescent-cells-while-preserving-beneficial-ones Paper DOI - https://doi.org/10.18632/aging.206375 Corresponding author - Dong Yang – yangdong@wchscu.cn Abstract video - https://www.youtube.com/watch?v=HkJRwF8mp4A Keywords - cellular senescence, aging mechanisms, functional heterogeneity, precision anti-aging To learn more about the journal, please visit www.Aging-US.com​​ and connect with us on social media at: Bluesky - bsky.app/profile/aging-us.bsky.social ResearchGate - www.researchgate.net/journal/Aging-1945-4589 X - twitter.com/AgingJrnl Facebook - www.facebook.com/AgingUS/ Instagram - www.instagram.com/agingjrnl/ LinkedIn - www.linkedin.com/company/aging/ Reddit - www.reddit.com/user/AgingUS/ Pinterest - www.pinterest.com/AgingUS/ YouTube - www.youtube.com/@Aging-US Spotify - open.spotify.com/show/1X4HQQgegjReaf6Mozn6Mc MEDIA@IMPACTJOURNALS.COM

Efforts to improve metabolic health through dietary interventions often come with trade-offs. Some approaches that reduce obesity or extend lifespan in laboratory models can also negatively affect other tissues, including bone. One example is sulfur amino acid restriction (SAAR), a diet low in methionine and lacking cysteine that has repeatedly shown strong anti-obesity effects in animal studies. However, despite these promising metabolic benefits, SAAR has also been associated with reduced bone mineral density, weaker bones, and increased marrow fat accumulation. This has led researchers to ask whether the metabolic benefits of SAAR can be separated from its harmful skeletal effects. A new research paper was published in Volume 18 of Aging-US, 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.” The researchers investigated whether those metabolic benefits could be achieved without the same harmful effects on bone. The study was led by first author Naidu B. Ommi and corresponding author Sailendra N. Nichenametla from the Orentreich Foundation for the Advancement of Science Inc., in collaboration with Dwight A. L. Mattocks from the same institution and Mark C. Horowitz from the Yale University School of Medicine. Full blog - https://aging-us.org/2026/05/glutathione-pathway-may-hold-the-key-to-safer-anti-obesity-interventions/ Paper 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 — May 12, 2026 — A new #research paper was #published in Volume 18 of Aging-US on May 4, 2026, titled “Host immunosenescence compromises Mycobacterium tuberculosis clearance.” The study was led by first author Falak Pahwa and corresponding author Ranjan Kumar Nanda from the International Centre for Genetic Engineering and Biotechnology (ICGEB), New Delhi, India. In this study, the authors investigated how aging alters immune responses during tuberculosis infection and treatment. Tuberculosis remains one of the world's deadliest infectious diseases, and older adults are particularly vulnerable due to immunosenescence, the gradual decline of immune function that occurs with aging. Despite the growing burden of tuberculosis in aging populations worldwide, most experimental models continue to rely on young adult animals that do not accurately reflect immune aging. Using multiple age groups of C57BL/6 mice, the researchers examined how aging affects the body's ability to control Mycobacterium tuberculosis during treatment with rifampicin and isoniazid (RIF-INH), two cornerstone anti-tuberculosis drugs. While young and older mice initially showed similar bacterial burden following infection, older mice demonstrated significantly delayed bacterial clearance in the lungs during the early phase of treatment. Importantly, the study identified several age-associated immune abnormalities linked to impaired bacterial clearance. Older mice exhibited chronic inflammatory signaling, altered T cell responses, accumulation of T-follicular cytotoxic (TFC)-like cells, and evidence of mitochondrial dysfunction within immune cells. Proteomic analysis of splenic CD4+CD44+ T cells further revealed dysregulation of mitochondrial proteins involved in cellular metabolism and immune function. “Collectively, these findings suggest that age-associated immune alterations may disrupt immunometabolic pathways, thereby contributing to the delayed Mtb clearance.” The researchers also observed that older mice maintained elevated inflammatory cytokine levels and developed persistent lung inflammation even after treatment had begun. At the same time, key protective immune responses appeared functionally impaired, suggesting that aging may disrupt the balance between inflammation and effective pathogen control. Together, these findings suggest that age-related immunometabolic dysfunction may play a major role in the reduced treatment response observed in older hosts. Notably, the study found that delayed bacterial clearance in older mice did not appear to result primarily from liver toxicity or impaired drug metabolism. Instead, the evidence suggested that age-related immune dysfunction itself was the dominant factor limiting effective bacterial elimination during therapy. The paper further highlights the emerging importance of mitochondrial health in immune cell function during aging. The authors propose that targeting age-associated immunometabolic defects and mitochondrial dysfunction may represent a promising strategy for improving tuberculosis treatment outcomes in elderly populations. Overall, this study provides new insight into why older adults experience poorer tuberculosis outcomes despite receiving standard therapy. As global populations continue to age, understanding how immunosenescence alters infectious disease responses may become increasingly important for the development of more effective treatment strategies and age-adapted therapeutic interventions. DOI - https://doi.org/10.18632/aging.206374 Corresponding author - Ranjan Kumar Nanda - ranjan@icgeb.res.in Abstract video - https://www.youtube.com/watch?v=isPD8ZmUjv8 Website - https://www.Aging-US.com​​ MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — May 7, 2026 — A new #research paper was #published in Volume 18 of Aging-US on April 24, 2026, titled “The BHARAT study: a multi-modal, multi-omics investigation of aging signatures in the Indian population.” The study was led by first author Suramya Asthana and corresponding author Deepak Kumar Saini from the Indian Institute of Science (IISc). The authors introduce the BHARAT Study (Biomarkers of Healthy Aging, Resilience, Adversity, and Transitions), India's first large-scale, discovery-driven multi-omics cohort focused on understanding biological aging in the Indian population. The initiative was developed to address a major gap in aging research, as most existing biological age models and aging datasets have been derived primarily from Western populations. The BHARAT study is a multi-center, cross-sectional observational cohort that integrates clinical, molecular, lifestyle, and environmental data from participants across diverse demographic groups in India. The initiative aims to enroll healthy volunteers spanning multiple age groups, with balanced rural-urban and sex representation. Biological samples—including blood, urine, stool, cheek swabs, and hair—will undergo extensive multi-omics profiling, including epigenomics, proteomics, metabolomics, lipidomics, metagenomics, and immune phenotyping. “By generating interoperable, high-resolution data suited for mechanistic modelling and machine learning, BHARAT contributes a resource of global relevance that would be capable of refining universal models of aging biology while revealing novel, population-specific pathways that inform prevention and intervention strategies.” The initiative uses a hub-and-spoke framework centered at the Indian Institute of Science, which serves as the central hub for biobanking, multi-omics analysis, computational integration, and AI-driven modeling. Clinical and community partners across India contribute participant recruitment, clinical assessments, and biological sampling, enabling the study to capture the country's extraordinary genetic, environmental, dietary, and socioeconomic diversity. A major focus of the study is the development of population-specific biological aging signatures and predictive models tailored to Indian populations. Researchers aim to identify biomarkers associated with resilience, frailty, and age-related decline while also recalibrating biological clocks that may not accurately reflect aging trajectories in non-Western populations. The study further seeks to establish standardized reference datasets and create scalable infrastructure for future longitudinal aging research in India. Importantly, the BHARAT study combines untargeted discovery-based omics technologies with advanced artificial intelligence and machine learning approaches. By integrating molecular data with clinical and lifestyle information, the initiative aims to improve understanding of how biological aging is shaped by genetics, environment, nutrition, infection burden, and social determinants of health. Overall, this study establishes a comprehensive framework for aging research in one of the world's most diverse populations. By generating large-scale, population-specific biological datasets, the BHARAT initiative may help advance precision aging research, improve risk prediction models, and support the development of more personalized approaches to healthy aging and disease prevention. DOI - https://doi.org/10.18632/aging.206373 Corresponding author - Deepak Kumar Saini - deepaksaini@iisc.ac.in Abstract video - https://www.youtube.com/watch?v=qH2AbitDURQ Website - https://www.Aging-US.com​​ MEDIA@IMPACTJOURNALS.COM

BUFFALO, NY — May 5, 2026 — A new #research paper was #published in Volume 18 of Aging-US on April 13, 2026, titled “Cross species activity of TERT human telomerase component.” The study was led by co–first authors Raúl Sánchez-Vázquez and Paula Martínez, with María A. Blasco serving as corresponding author, from the Spanish National Cancer Centre (CNIO), Madrid, Spain. In this study, the researchers explored a key question in aging and regenerative medicine: can the human telomerase protein function effectively in other species commonly used in preclinical research? Telomerase plays a central role in maintaining chromosome integrity by preventing telomere shortening—a process closely linked to cellular aging and disease. To investigate this, the team introduced the human telomerase catalytic subunit (TERT) into primary lung fibroblasts from several mammalian species, including monkey, pig, rabbit, rat, dog, and mouse. They then assessed both biochemical activity and the ability of telomerase to extend telomeres over time. The results revealed a clear distinction between biochemical compatibility and true biological function. In vitro, human TERT was able to form active complexes with telomerase RNA from several species, including monkey, pig, rabbit, and rat. However, this activity did not always translate into effective telomere maintenance in living cells. Notably, only human and non-human primate cells showed progressive telomere lengthening over time. In contrast, other species—even those showing initial enzymatic activity—failed to sustain telomere extension during long-term culture. In some cases, telomeres continued to shorten, suggesting that functional integration of telomerase depends on additional species-specific factors. The study also uncovered important limitations in commonly used animal models. Mouse and canine cells did not support human TERT activity, and in some cases, expression of the human enzyme led to reduced cell viability and signs of cellular stress. “These results reveal that only non-human primate cells support full functional activity of the human telomerase protein in a cellular context, underscoring their suitability as preclinical models for telomerase-based therapeutic strategies.” Importantly, the findings highlight that successful telomerase activity in a test tube does not necessarily reflect what happens inside a living cell. The recruitment, regulation, and function of telomerase depend on a complex network of interacting proteins and cellular processes, many of which differ across species. Overall, this study provides important insight into the challenges of translating telomerase-based therapies from preclinical models to humans. By identifying non-human primates as the most compatible system, the work offers a clearer path forward for developing therapies aimed at treating telomere-related diseases and age-associated conditions. DOI - https://doi.org/10.18632/aging.206372 Corresponding author - Maria A. Blasco - mblasco@cnio.es Abstract video - https://www.youtube.com/watch?v=XxjjId5i_Ww Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, telomeres, telomerase 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

On April 25, 2026, the NOVA (Neuroscience of Vitality and Aging) Conference brought together a dynamic and interdisciplinary audience in Boston, MA. With over 600 attendees spanning students, researchers, clinicians, investors, and patient advocates, the event highlighted both the complexity of brain aging and the growing momentum behind efforts to better understand and treat neurodegenerative diseases. In the opening keynote, Dr. Joanne Smikle of the American Brain Foundation emphasized the need to remember the “why” behind this research. She highlighted the power of intentional collaboration and the belief that breakthroughs in one neurological disease may translate to others. Even small monthly contributions as little as $10.00 can collectively drive meaningful progress. Full recap - https://aging-us.org/2026/04/aging-us-supports-the-nova-conference-2026/ 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 — April 29, 2026 — A new #research paper was #published in Volume 18 of Aging-US on April 10, 2026, titled “Stage-dependent transcriptomic changes in human dermal fibroblast senescence model.” The study was led by first author Michiko Kudo from the University of Tokyo and DHC Corporation Laboratories and corresponding author Shuichi Asakawa from the University of Tokyo. In this work, the researchers took a closer look at how gene expression changes as cells age, focusing on human dermal fibroblasts—a widely used model for studying aging in skin and connective tissues. While cellular senescence is known to play a central role in aging, the timing and progression of molecular changes during this process have remained difficult to define. To explore this, the team developed a stepwise model of replicative senescence, categorizing cells into three stages—young, middle, and old—based on their cumulative number of divisions. This approach allowed them to capture the gradual nature of aging, rather than relying on acute stress models that may overlook early-stage transitions. One of the more interesting findings was that the “middle” stage—often overlooked—is not just a simple midpoint, but a biologically active transition phase. Although gene expression profiles in young and middle cells appeared similar at first glance, a closer look showed that important molecular changes had already begun during this phase. In particular, genes involved in immune and inflammatory responses were activated early, even before cells reached full senescence. This suggests that aging-related inflammation may begin much earlier than previously appreciated, gradually intensifying as cells progress toward the late stage. At the same time, genes responsible for maintaining basic cellular functions—such as protein synthesis, cell structure, and adhesion—showed a progressive decline as aging advanced. Together, these changes suggest a shift in cellular priorities, where stress and inflammatory signals increase while maintenance and repair functions gradually decline. To better understand these patterns, the researchers combined transcriptomic analysis with network and matrix factorization approaches. These methods revealed distinct gene expression programs associated with different stages of aging, including early immune activation, mid-stage extracellular remodeling, and late-stage functional decline. “These findings suggest that immune–inflammatory responses are engaged from early senescence, whereas cell adhesion and maintenance pathways decline progressively.” Importantly, the results point to the middle stage of senescence as a potential window for intervention. Unlike fully senescent cells, which exhibit more stable and potentially irreversible changes, cells in this transitional phase may retain some degree of plasticity, making them more responsive to therapeutic strategies. Overall, this study offers a clearer picture of how aging unfolds at the molecular level. By identifying stage-specific changes in gene expression, the authors provide new insight into the early drivers of cellular senescence and highlight potential targets for delaying or modifying age-related decline. DOI - https://doi.org/10.18632/aging.206371 Corresponding author - Shuichi Asakawa - asakawa@g.ecc.u-tokyo.ac.jp Abstract video - https://www.youtube.com/watch?v=DZNfYmj4DW8 Website - https://www.Aging-US.com​​ 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 has long been linked to a range of biological processes, including cellular senescence, epigenetic changes, and chronic tissue remodeling. Yet, these explanations often describe what happens during aging rather than why certain age-related diseases, such as fibrosis, continue to progress over time. In conditions like idiopathic pulmonary fibrosis (IPF), a key question remains: what drives the persistent activation of cells that should normally return to a resting state after injury? Increasing attention has turned to the interaction between cellular signaling pathways and epigenetic regulation as a potential explanation. Understanding how these processes work together to control gene expression and cell behavior is becoming an important focus in uncovering the mechanisms behind age-related disease. A new research paper was published in Volume 18 of Aging-US, titled “P38 MAPK is involved in epigenetic regulation of fibrotic genes in replication induced senescence in lung fibroblasts.” The study was led by first author Shan Zhu and 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), in collaboration with Jennifer Q. Zhou, Kan Wang, and Ming-lei Guo from the same institution. Full blog - https://aging-us.org/2026/04/p38-mapk-driven-epigenetic-regulation-identified-as-a-key-mechanism-in-lung-fibrosis/ Paper 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

BUFFALO, NY — April 27, 2026 — A new #hypothesis paper was #published in Volume 18 of Aging-US on April 8, 2026, titled “From Hydra to rotifer and beyond: implications for human aging and delayed senescence.” The study was led by first and corresponding author Michael Bordonaro from the Geisinger College of Health Sciences. In this work, the author explores a bold and testable hypothesis centered on two very different invertebrate models of aging: the freshwater cnidarian Hydra and the rotifer Brachionus manjavacas. Hydra are well known for their remarkable ability to maintain tissue integrity over time through continuous stem cell renewal, effectively avoiding many of the hallmarks of aging under laboratory conditions. In contrast, rotifers represent the opposite end of the biological spectrum, with short lifespans, fixed somatic cell numbers, and a predictable pattern of age-related decline. Building on these contrasts, the paper proposes that introducing Hydra-like gene expression patterns into rotifers could delay senescence and extend healthspan. The hypothesis focuses in particular on conserved molecular pathways, including the transcription factor FoxO, which plays a central role in maintaining stem cell function and cellular resilience. Rather than attempting to recreate full stem cell renewal in rotifers—an organism with a fixed adult cell number—the proposed strategy emphasizes improving cellular maintenance, stress resistance, and proteostasis within existing cells. The paper outlines an iterative experimental framework, beginning with targeted genetic manipulation in rotifers and extending to more complex organisms such as Daphnia and mouse models. This stepwise approach is designed to identify which elements of the Hydra genetic program are truly responsible for its resistance to aging, while also allowing researchers to monitor potential trade-offs, including increased risk of uncontrolled cell growth. “We hypothesize that delayed senescence at the organismal level is possible through recapitulation of Hydra-like patterns of gene expression in rotifers, and that data obtained may help generate hypotheses for somatic interventions and prioritize pathways for mammalian validation in future studies.” Importantly, the author emphasizes that complete elimination of aging is unlikely in complex organisms due to evolutionary and biological constraints. Instead, the goal is more realistic: extending healthspan and delaying the onset of age-related decline. The paper also highlights the importance of balancing potential benefits with risks, particularly the possibility that enhancing cellular renewal pathways could increase susceptibility to neoplasia. Overall, this study presents a conceptual and experimental roadmap for translating insights from simple organisms into strategies that may eventually inform human aging research. By bridging the gap between negligible senescence and rapid aging models, the work provides a fresh perspective on how conserved biological mechanisms might be harnessed to improve health across the lifespan. DOI - https://doi.org/10.18632/aging.206370 Corresponding author - Michael Bordonaro - mbordonaro1@geisinger.edu Abstract video - https://www.youtube.com/watch?v=YGzYf3W5jNA 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 — April 23, 2026 — A new #research paper was #published in Volume 18 of Aging-US on April 7, 2026, titled “Association of epigenetic age acceleration with MRI biomarkers of aging and Alzheimer's disease neurodegeneration.” The study was led by first and corresponding author Linda K. McEvoy from the Kaiser Permanente Washington Health Research Institute, in collaboration with a multidisciplinary team of researchers across leading institutions in the United States and Europe. In this study, the researchers examined whether epigenetic measures of biological aging are associated with structural brain changes linked to aging and Alzheimer's disease. Using data from 1,196 older women enrolled in the Women's Health Initiative Memory Study, they analyzed five widely used epigenetic clocks and compared them with MRI-derived measures obtained approximately eight years later. The findings revealed a clear distinction between different aspects of aging. None of the epigenetic clocks were associated with accelerated brain aging as measured by the SPARE-BA index, a composite MRI marker of brain age. However, one specific clock—AgeAccelGrim2—was significantly associated with the Alzheimer's Disease Pattern Similarity Score (AD-PS), a validated imaging biomarker linked to increased risk of dementia. Further analyses suggested that this association was largely driven by epigenetic signatures related to smoking exposure. In particular, a DNA methylation marker reflecting cumulative smoking history was linked to reduced frontal and temporal lobe volumes—regions commonly affected in age-related neurodegeneration. Notably, no significant associations were observed with hippocampal or entorhinal cortex volumes, areas more directly implicated in early Alzheimer's pathology. “Taken together with prior findings, these results suggest that measures of epigenetic and brain age acceleration capture different aspects of biological aging, and that AgeAccelGrim2 is predictive of neurodegenerative changes associated with smoking that increase risk of dementia.” The study highlights the complexity of biological aging and underscores that not all aging biomarkers reflect the same underlying processes. While epigenetic clocks are increasingly used to estimate biological age, their relationship with brain structure appears to depend on the specific pathways they capture—particularly those influenced by environmental exposures such as smoking. Overall, these findings provide important insight into how molecular measures of aging relate to neuroimaging markers of brain health. By distinguishing between general brain aging and disease-related neurodegeneration, this work helps refine the use of epigenetic biomarkers in aging research and may support future efforts to identify individuals at risk for cognitive decline. DOI - https://doi.org/10.18632/aging.206369 Corresponding author - Linda K. McEvoy - linda.k.mcevoy@kp.org Abstract video - https://www.youtube.com/watch?v=kZiRjlKnnsI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206369 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, epigenetic clocks, brain age, biological aging, smoking, frontal lobe 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 — April 21, 2026 — A new meeting report was published in Volume 18 of Aging-US on April 6, 2026, titled “Toward actionable interventions in human aging (12th ARDD meeting, 2025).” The report was led by corresponding authors Aleksandr Dekan and Daniela Bakula from the University of Copenhagen, Denmark, in collaboration with an international group of researchers spanning academia, industry, and biotechnology. Bringing together experts from across the global aging research community, the 12th ARDD meeting focused on one central goal: moving beyond descriptive studies of aging toward interventions that can actively improve human healthspan. The discussions reflected a clear shift in the field—from understanding the hallmarks of aging to identifying the molecular mechanisms that can be targeted to modify them. Key presentations explored whether biological age can be reversed, highlighting the epigenome as a central regulator of cellular identity. Emerging evidence suggests that partial cellular reprogramming may restore youthful function, while systemic effects observed in preclinical models point to the possibility of organ-wide or even whole-body rejuvenation. The meeting also emphasized the importance of maintaining genomic integrity, with accumulating DNA damage linked to widespread transcriptional stress and age-associated functional decline. At the same time, chronic inflammation, metabolic dysfunction, and cellular senescence were consistently identified as major drivers of aging, reinforcing the need for integrated, multi-targeted therapeutic strategies. Advances in biomarker development were another major focus. Researchers presented new generations of biological aging clocks—ranging from organ-specific proteomic signatures to single-cell and imaging-based approaches—capable of predicting disease risk and monitoring intervention outcomes with increasing precision. In parallel, the integration of artificial intelligence into drug discovery is accelerating the development of novel therapeutics. From generative AI-designed proteins to platform-based identification of new drug targets, these approaches are helping bridge the gap between basic research and clinical application. “This focus is predicated on the hypothesis that aging is not solely a result of stochastic damage accumulation but may be a tractable, modifiable, and potentially reversible biological process amenable to intervention.” Beyond laboratory science, the meeting highlighted the growing importance of translational strategies, regulatory pathways, and investment models in bringing anti-aging therapies to market. A consensus emerged around a “disease-first” approach, in which targeting specific age-related conditions may provide a practical pathway for validating interventions that also influence underlying aging biology. Overall, the ARDD 2025 meeting underscored a major turning point in the field. Aging research is no longer confined to observation—it is increasingly positioned to deliver actionable interventions that could reshape how age-related diseases are prevented and treated. DOI - https://doi.org/10.18632/aging.206368 Corresponding authors - Aleksandr Dekan - adekan@sund.ku.dk, and Daniela Bakula - bakula@sund.ku.dk Video abstract - https://www.youtube.com/watch?v=LntAWVQMKqE 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 — April 17, 2026 — A new #research paper was #published in Volume 18 of Aging-US on April 3, 2026, titled “Modeling premature aging in yeast via the expression of Progerin.” The study was led by first author Zachery R. Belak from the University of Saskatchewan, and corresponding author Troy A.A. Harkness from the University of Saskatchewan and the University of Alberta. The team developed a yeast-based model to study premature aging by expressing Progerin, the toxic protein responsible for Hutchinson–Gilford Progeria Syndrome. Using genetically engineered yeast cells, they compared the effects of Progerin with its normal counterpart, Lamin A, to better understand how protein accumulation impacts cellular aging. Their findings show that Progerin expression leads to slower cell growth, increased genome instability, and a significant reduction in chronological lifespan. In contrast, Lamin A did not produce the same harmful effects, highlighting the specific role of Progerin in driving premature aging phenotypes. The study also demonstrates that Progerin accumulates in aging mother cells and remains more stable than Lamin A, suggesting a mechanism by which damaged or toxic proteins are retained during the aging process. These observations mirror what has been reported in human cells, reinforcing the relevance of this model system. “Taken together, expression of Progerin in yeast cells mimics what is observed in human cells, establishing yeast as a powerful model to discover genetic mechanisms driving premature and normal aging.” Overall, the researchers present a practical and efficient model for studying the biological mechanisms underlying premature aging. Their work provides a valuable platform for testing new strategies aimed at reducing toxic protein accumulation and improving cellular health during aging. DOI - https://doi.org/10.18632/aging.206367 Corresponding author - Troy AA. Harkness - taharkne@ualberta.ca Abstract video - https://www.youtube.com/watch?v=VYQKAJjgIb8 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206367 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, Hutchinson-Gilford Progeria Syndrome, yeast, Progerin, Lamin A, premature 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 — April 15, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 30, 2026, titled “A manually curated gene–phenotype catalogue for progeroid syndromes and premature aging.” The study was led by Nuša Likar and Tanja Kunej from the University of Ljubljana, Slovenia. The researchers developed a comprehensive, manually curated catalogue integrating data from 84 scientific publications and the OMIM database. The resulting resource systematically organizes genetic and clinical information on progeroid syndromes, linking 144 genes to 56 syndromes and 160 distinct clinical entities, making it one of the most extensive datasets in this field to date. Using genome–phenome association analysis and protein–protein interaction networks, the study reveals the complex genetic and phenotypic heterogeneity underlying premature aging disorders. The findings highlight strong enrichment in genome maintenance and DNA repair pathways, reinforcing their central role in aging biology. The catalogue also demonstrates how single genes, such as LMNA, can be associated with multiple syndromes, illustrating the pleiotropic nature of genetic variants in progeroid conditions and their broader relevance to human aging mechanisms. “Overall, this study provides a reference resource and framework to support future research into premature aging syndromes and their broader implications for understanding physiological aging.” Overall, the authors present a valuable framework for improving the classification, diagnosis, and study of rare premature aging disorders. Their work not only advances understanding of progeroid syndromes but also offers important insights into the biological processes that drive normal human aging. DOI - https://doi.org/10.18632/aging.206366 Corresponding author - Tanja Kunej - tanja.kunej@bf.uni-lj.si Abstract video - https://www.youtube.com/watch?v=Ov6Saz34ZpE Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206366 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, premature aging, progeroid syndromes, DNA repair, LMNA gene 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

In this episode of the Longevity & Aging Series (S4, E3), Dr. Ricardo Costeira of King's College London joins host Dr. Yuan Zhao of Queen Mary University of London to discuss a research paper he co-authored in Volume 17, Issue 12 of Aging-US, titled “Theobromine is associated with slower epigenetic ageing.” 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 Video interview - https://www.youtube.com/watch?v=in0z_QApqWQ Longevity & Aging Series - https://www.aging-us.com/longevity About Dr. Yuan Zhao - https://www.qmul.ac.uk/sbbs/staff/yuan-zhao.html Abstract video - https://www.youtube.com/watch?v=S0P1USM8L6E Abstract Theobromine, a commonly consumed dietary alkaloid derived from cocoa, has been linked to extended lifespan in model organisms and to health benefits in humans. We examined associations between circulating levels of theobromine intake, measured using serum metabolomics, and blood-based epigenetic markers of biological ageing in two European human population-based cohorts. Serum theobromine levels were significantly associated with reduced epigenetic age acceleration, as measured by GrimAge (p < 2e-7) and DNAmTL (p < 0.001) in 509 individuals from the TwinsUK cohort, and both signals replicated in 1,160 individuals from the KORA cohort (p = 7.2e-08 and p = 0.007, respectively). Sensitivity analyses including covariates of other cocoa and coffee metabolites suggest that the effect is specific to theobromine. Our findings indicate that the reported beneficial links between theobromine intake on health and ageing extend to the molecular epigenetic level in humans. 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

Aging has long been attributed to a range of biological processes, including DNA damage, telomere shortening, and mitochondrial dysfunction. Yet, these frameworks often describe downstream consequences rather than a single unifying cause. Despite decades of research, a central question remains unresolved: what ultimately determines lifespan across species? Increasing attention has turned to cellular energy metabolism—particularly pathways responsible for rapid ATP generation—as a potential key driver. Understanding how these metabolic changes unfold over time, and how they influence survival, regeneration, and disease, remains a major challenge in aging biology. A new research perspective published in Volume 18 of Aging-US introduces a unifying concept in aging biology, titled “A decline in glycolytic ATP production is the fundamental mechanism limiting lifespan; species with an optimal rate of decline over time survived.” Full blog - https://aging-us.org/2026/04/decline-in-glycolytic-atp-production-proposed-as-a-fundamental-mechanism-limiting-lifespan/ Paper DOI - https://doi.org/10.18632/aging.206356 Corresponding author - Akihiko Taguchi - taguchi@fbri.org Abstract video - https://www.youtube.com/watch?v=rA23radaoqI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206356 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - hypothesis, aging, glycolytic ATP production, lifespan, Heterocephalus glaber 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

Each month, we will highlight a paper published in Aging-US chosen as the “Editors' Choice.” These selections are handpicked by our editors and accompanied by a brief summary, showcasing research with significant impact and novel insights in aging and age-related diseases. _____ In this study, titled “Plant-based dietary patterns are associated with slower epigenetic aging,” the researchers examined whether plant-based dietary patterns are linked to biological aging in large, diverse U.S. populations. Using data from the Atherosclerosis Risk in Communities (ARIC) Study and National Health and Nutrition Examination Survey (NHANES), they analyzed several versions of plant-based diet scores that reflect higher intake of plant foods and lower intake of animal products, as well as distinctions between healthy and less healthy plant-based foods. They then compared these dietary patterns with DNA methylation-based “epigenetic clocks,” which estimate biological age, including GrimAge2, PhenoAge, and HannumAge. The results showed that greater adherence to overall plant-based diets, provegetarian diets, and especially healthy plant-based diets was consistently associated with slower epigenetic aging, meaning participants appeared biologically younger than their chronological age. In contrast, diets higher in less healthy plant-based foods did not show the same benefits. The findings suggest that diets emphasizing whole plant foods and limiting animal products may help slow biological aging at the molecular level. DOI - https://doi.org/10.18632/aging.206362 Corresponding author - Hyunju Kim - hyunjuk1@uw.edu Abstract video - https://www.youtube.com/watch?v=FcJ7oEZ-KFk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206362 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, plant-based diets, DNA methylation, epigenetic aging, all-cause mortality, middle-aged adults 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 — April 9, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 27, 2026, titled “ATF5 is required for the maintenance of mitochondrial homeostasis and skeletal muscle health during aging.” Led by first author Victoria C. Sanfrancesco and corresponding author David A. Hood, both from the Muscle Health Research Centre, School of Kinesiology and Health Science, York University, Toronto, Ontario, Canada, the study investigated the role of activating transcription factor 5 (ATF5) in regulating mitochondrial quality control and skeletal muscle function during aging. Using young and aged mouse models with and without ATF5 expression, the researchers examined how this transcription factor contributes to mitochondrial homeostasis, protein turnover, and stress response pathways. The analysis focused on key mechanisms such as the integrated stress response (ISR) and mitochondrial unfolded protein response (UPRmt), which are essential for maintaining mitochondrial integrity. The authors found that ATF5 plays a critical role in coordinating mitochondrial quality control and adaptive stress signaling in skeletal muscle. Notably, the absence of ATF5 prevented the typical age-related decline in muscle mass but resulted in increased muscle fatigability and elevated mitochondrial reactive oxygen species (ROS) production. Additionally, the loss of ATF5 disrupted normal stress-response signaling and altered protein degradation pathways, highlighting its importance in maintaining muscle function with age. “Collectively, these results suggest that ATF5 functions to maintain mitochondrial quality control and muscle endurance at the expense of muscle mass, and its absence attenuates the normal compensatory stress response to contractile activity with age.” The authors conclude that while ATF5 contributes to preserving mitochondrial function and endurance capacity, its role in regulating muscle mass and stress adaptation is complex. Further studies are needed to clarify how modulation of ATF5 and related pathways could be leveraged to improve muscle health and mitigate age-related decline in mitochondrial function and physical performance. DOI - https://doi.org/10.18632/aging.206365 Corresponding author - David A. Hood - dhood@yorku.ca Abstract video - https://www.youtube.com/watch?v=u2OeppqIPN4 Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206365 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, skeletal muscle, ATF5, mitochondria, stress response 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 — April 7, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 26, 2026, titled “Effects of intravenous furosemide plus small-volume hypertonic saline solutions on inflammatory, remodelling markers and epigenetics signatures of patients with congestive acute decompensated heart failure (ADHF).” Led by first author Mario Daidone from University Hospital, Policlinico, Paolo Giaccone, and the University of Palermo, with corresponding author Antonino Tuttolomondo from University Hospital, Policlinico, Paolo Giaccone, and University of Palermo, the randomized trial compared i.v. furosemide plus small-volume hypertonic saline solution (HSS) with i.v. furosemide alone in patients with acute decompensated heart failure due to reduced ejection fraction. The study enrolled 200 subjects, randomly assigning 107 to furosemide plus HSS and 93 to furosemide alone. The authors found that patients treated with i.v. furosemide plus HSS showed lower increases in inflammatory and remodeling biomarkers after saline load, including IL-6, hsTnT, sST2, galectin-3, and NT-proBNP, and the intervention was associated with reduced miR181b expression compared with furosemide alone. These findings suggest that adding small-volume hypertonic saline to loop diuretic therapy may influence both circulating biomarkers and miRNA-related epigenetic signatures in acute heart failure. “Nevertheless, the possible effects of the i.v. furosemide + HSS treatment on natriuretic and inflammatory markers of heart failure deserve further confirmation, whereas the effects of this type of treatment on epigenetic signatures of pathologic mechanisms involved in the left ventricular dysfunction involved in AHF pathogenesis seem to be still not studied.” The authors note that this was a randomized trial in a specific ADHF population, so additional studies will be needed to confirm the durability of the biomarker changes, define the optimal patient groups, and determine whether these molecular effects translate into improved clinical outcomes. Future work may also clarify how the saline strategy interacts with cardiac remodeling and miRNA regulation in larger and more diverse heart failure cohorts. DOI - https://doi.org/10.18632/aging.206364 Corresponding author - Antonino Tuttolomondo - bruno.tuttolomondo@unipa.it Abstract video - https://www.youtube.com/watch?v=EG65XlcDJ3U Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206364 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, heart failure, acute decompensated heart failure, furosemide, hypertonic saline solution 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 — April 2, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 24, 2026, titled “Age-specific relationship between the modulation of brain dynamics in response to task demands and bimanual performance.” Led by first author Sara Magalhães Ferreira from Hasselt University, with corresponding author Koen Cuypers from Hasselt University and KU Leuven, the study examined how age affects BOLD variability and its modulation with task demands during a bimanual task. The authors used fMRI in 22 younger and 23 older healthy adults who performed three increasingly complex task conditions. The authors found that older adults showed higher BOLD variability in cerebellar lobule VIIIb and greater modulation across task conditions in sensorimotor and cerebellar regions. Modulation of BOLD variability predicted performance in an age- and region-dependent manner: in younger adults, reduced modulation in sensorimotor and visuospatial areas correlated with better performance, whereas in older adults, increased modulation in the inferior and superior parietal lobules was linked to higher performance. Across groups, better outcomes were associated with greater modulation in the middle occipital gyrus but lower modulation in cerebellar Crus I. “In sum, this study highlights the potential role of BOLD variability modulation in shaping bimanual performance during aging.” The authors note that, while the age-related differences in BOLD dynamics were clear, they did not find robust evidence supporting a brain-behavior relationship in bimanual performance, which limits how directly the neural findings can be interpreted behaviorally. They recommend future work using multimodal imaging, longitudinal designs, and studies that examine both cognitive and motor domains within the same participants to determine whether variability modulation reflects aging, experience, intervention, or broader cross-functional signatures of aging. DOI - https://doi.org/10.18632/aging.206363 Corresponding author - Koen Cuypers - koen.cuypers@uhasselt.be Abstract video - https://www.youtube.com/watch?v=3TbcGFCZV9s Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206363 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, bimanual coordination, Bimanual Tracking Task, BOLD variability, task modulation 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

Inflammation is a double-edged sword. It defends the body against infection and injury, yet when it becomes chronic, it can accelerate aging and fuel the very diseases that shorten human life. For decades, scientists have observed that people with higher levels of inflammatory markers like interleukin-6 (IL6) and C-reactive protein (CRP) tend to have shorter lifespans. But the critical question has always been: does inflammation cause mortality, or does it merely reflect underlying disease? A research paper, titled “Causal effects of inflammation on long-term mortality: A mendelian randomization study” was published in Volume 18 of Aging-US by an international team of researchers, provides a definitive answer by using a powerful genetic technique to untangle cause from effect. The team's investigation demonstrates that the IL6 inflammatory pathway has a direct causal impact on human survival—but with a surprising twist: two components of the same pathway pull in opposite directions. Full blog - https://aging-us.org/2026/04/il6-and-il6r-opposing-forces-of-inflammation-that-shape-human-survival/ 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

BUFFALO, NY — March 31, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 20, 2026, titled “Plant-based dietary patterns are associated with slower epigenetic aging.” Led by first and corresponding author Hyunju Kim from the Department of Epidemiology and the Cardiovascular Health Research Unit, Department of Medicine, University of Washington, the study examined whether four plant-based diet indices — overall PDI, provegetarian diet, healthy PDI, and unhealthy PDI — were associated with DNA methylation-based measures of epigenetic aging. The authors analyzed data from the Atherosclerosis Risk in Communities (ARIC) Study (n = 2,810) and the National Health and Nutrition Examination Survey (NHANES, n = 2,056), and assessed associations with GrimAge2, HannumAge, and PhenoAge. The researchers found that each standard deviation higher in the overall PDI, provegetarian diet, and healthy PDI was associated with decelerated GrimAge2, while higher overall PDI and provegetarian diet were also associated with decelerated PhenoAge and HannumAge. By contrast, unhealthy PDI was not significantly associated with epigenetic aging. The findings suggest that plant-rich dietary patterns, especially those emphasizing healthier plant foods, may be linked to slower biological aging in largely non-vegetarian populations. “No significant association was observed for unhealthy PDI and any of the DNA methylation-based aging.” The authors note that these are observational data and do not establish causality. They call for longitudinal and interventional studies to determine whether sustained adherence to healthy plant-based dietary patterns can directly influence epigenetic aging and related health outcomes over time. DOI - https://doi.org/10.18632/aging.206362 Corresponding author - Hyunju Kim - hyunjuk1@uw.edu Abstract video - https://www.youtube.com/watch?v=FcJ7oEZ-KFk Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206362 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, plant-based diets, DNA methylation, epigenetic aging, all-cause mortality, middle-aged adults 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 25, 2026 — A new #review was #published in Volume 18 of Aging-US on March 18, 2026, titled “What are the effects of exergames on the mood states of older people? A systematic review of experimental studies, impacts on mental health and recommendations.” Led by Camile de Bem Gaspar and Whyllerton Mayron da Cruz, with corresponding author Alexandro Andrade, all from the Laboratory of Sport and Exercise Psychology, Human Movement Sciences Graduate Program, College of Health and Sport Science of the Santa Catarina State University (UDESC) in Florianópolis, Brazil, the review examined whether exergames can influence mood in older adults. The authors followed systematic review and meta-analysis methods, screened 651 studies, and found nine that met the inclusion criteria, representing 325 participants aged 61 to 78.9 years. The review found that exergames were associated with better mood outcomes, including reductions in tension, anger, fatigue, confusion, and depressive symptoms, while also promoting engagement, immersion, and socialization. In the studies that measured mood more broadly, participants described exergames as improving well-being and emotional state, and no included study reported worsened mood after participation. “The results indicate that the practice of exergames had a positive effect on the mood of older adults.” The authors note, however, that the evidence base remains small and heterogeneous, with only nine eligible trials and several different mood measures used across studies. They call for longer-term interventions, larger and more diverse samples, and additional home-based or low-cost exergame studies to determine how durable the benefits are and how best to recommend them for older adults in real-world settings. DOI - https://doi.org/10.18632/aging.206361 Corresponding author - Alexandro Andrade - alexandro.andrade.phd@gmail.com Abstract video - https://www.youtube.com/watch?v=mNBh_alqVRI Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206361 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, electronic games, older adults, BRUMS, mental health, physical activity 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 23, 2026 — A new #research paper was #published in Volume 18 of Aging-US on March 12, 2026, titled “Blood biochemical and gut microbiotic neural network models forecasting human biological age.” Led by Anastasia A. Kobelyatskaya from the Russian Clinical Research Center for Gerontology, Pirogov Russian National Research Medical University, and the Institute of Biology of Aging and Healthy Longevity Medicine with Preventive Medicine Clinic, Petrovsky Russian Research Centre of Surgery — with corresponding author Alexey Moskalev from the Institute of Biology of Aging and Healthy Longevity Medicine with Preventive Medicine Clinic, Petrovsky Russian Research Centre of Surgery — the study builds a gender-specific biochemical model (seven routine clinical markers, e.g., cystatin-C, IGF-1, DHEAS, plus sex-specific sets) and a microbiota model (45 species measured by full-length 16S sequencing). Both models were trained and tested on the same 637-person dataset and achieved mean absolute errors of around six years and R² values above 0.8. The team emphasised interpretability: they applied SHapley Additive exPlanations (SHAP) to convert each model from a “black box” into a more interpretable tool, showing how individual predictors (for example, DHEAS, cystatin-C, NT-proBNP in the blood model, and species such as Blautia obeum in the microbiota model) shift predicted age in years for a given individual. The biochemical clock yielded a small (clinically accessible) predictor set (7 markers) to ease clinical translation, while the microbiota clock used a 45-species signature and highlighted microbiome taxa whose abundance gradients correlate with predicted microbiotic age. “As the proposed models possess both global and local explainability, they hold future potential for application in monitoring the effectiveness of various interventions in clinical trials.” The authors note limitations and next steps: the cohort was restricted to a Caucasian population, and the microbiota model requires sequencing resources that may limit immediate clinical rollout. They call for external validation in larger, ethnically diverse cohorts, prospective testing to link model predictions to health outcomes, and application of the explainable models to monitor responses in intervention trials (for example, lifestyle, diet, or drug studies) where a change in predicted biological age would be an early, interpretable signal of benefit. DOI - https://doi.org/10.18632/aging.206360 Corresponding author - Alexey Moskalev - amoskalev@med.ru Abstract video - https://www.youtube.com/watch?v=wg3YEwXMKWY Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206360 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, biological age, blood biochemistry, gut microbiome, neural network 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

Dr. David Gems from University College London joins new host Dr. Yuan Zhao from Queen Mary University of London to discuss a review they co-authored in Volume 17, Issue 12 of Aging-US, titled “Aging as a multifactorial disorder with two stages.” DOI - https://doi.org/10.18632/aging.206339 Corresponding author - David Gems - david.gems@ucl.ac.uk Video interview - https://www.youtube.com/watch?v=JqZuAm7I4oQ Longevity & Aging Series - https://www.aging-us.com/longevity About Dr. Yuan Zhao - https://www.qmul.ac.uk/sbbs/staff/yuan-zhao.html Abstract video - https://www.youtube.com/watch?v=d4TSI4Ot3yM Abstract Aging (senescence) is characterized by development of diverse senescent pathologies and diseases, leading eventually to death. The major diseases of aging, including cardiovascular disease, cancer and chronic obstructive pulmonary disease (COPD), are multifactorial disorders, resulting from complex interactions between multiple etiologies. Here we propose a general account of how different determinants of aging can interact to generate late-life disease. This account, initially drawn from studies of the nematode Caenorhabditis elegans, depicts senescence as the product of a two-stage process. The first stage involves the diverse causes of disease prior to aging, that cause disruption of normal biological function. These include infection, mechanical injury and mutation (somatic and inherited). Second, etiologies largely confined to aging: deleterious, late-life consequences of evolved wild-type gene action, including antagonistic pleiotropy. Prior to aging, diverse insults lead to accumulation of various forms of injury that is largely contained, preventing progression to major pathology. In later life, wild-type gene action causes loss of containment of latent disruptions, which form foci for pathology development. Pathologies discussed here include osteoarthritis, cancer, late-life recrudescence of infection, and consequences of late-acting deleterious mutations. Such latent injury foci are analogous to seeds which in later life, in the context of programmatic senescent changes, germinate and develop into disease. 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 — March 18, 2026 — A new #editorial was #published in Volume 18 of Aging-US on March 10, 2026, titled “Healthy life extension: Geroscience's north star.” Led by David A. Barzilai — who is affiliated with Geneva College of Longevity Science, Healthspan Coaching LLC (Barzilai Longevity Consulting), and Harvard Medical School — the editorial pays tribute to the late Mikhail Blagosklonny and states that geroscience should adopt healthy life extension (measured as health-adjusted survival such as HALE and QALYs) as its primary objective rather than treating lifespan and healthspan as competing goals. Dr. Barzilai urges clearer outcome priorities, disciplined evidence in mammals, and coordinated investment that matches the field's potential to delay multimorbidity and extend high-quality years of life. The piece reviews data showing that increases in life expectancy have outpaced gains in healthy life expectancy and summarizes calls to measure success by health-adjusted longevity rather than biomarkers alone. It highlights examples where targeting conserved aging pathways produced replicable lifespan gains in mammals (for example, rapamycin in mice) and notes early human-facing signals (for example, mTOR inhibition improving influenza vaccine responses in older adults) that illustrate how aging-biology interventions can be clinically legible on shorter timelines. The editorial also frames the practical challenge: while lifespan evidence is ideal, human trials must use rigorous, meaningful endpoints that map to delayed multimorbidity, preserved function, and resilience. “Geroscience is for healthy life extension. We should stop pretending that lifespan and healthspan compete.” Dr. Barzilai calls for a “moonshot”-level commitment to aging biology that includes larger, better-funded basic programs, clinical trials with health-adjusted survival endpoints, and translational pipelines able to move robust mammalian lifespan findings toward human studies. He stresses the need for replicable mammalian lifespan data paired with human endpoints that reflect quality of life and independence. The editorial closes with a direct pledge in honor of Dr. Blagosklonny's legacy, in part to make healthy life extension the field's north star and measure success in years worth living. DOI - https://doi.org/10.18632/aging.206359 Corresponding author - David A. Barzilai - d.barzilai@gcls.study Intro video - https://www.youtube.com/watch?v=_MwFvDg7Ejw Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.206359 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, geroscience, longevity, healthspan, longevity medicine, healthy life 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 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 aging of an organism is reflected not only in the function of its organs but also in the molecular signatures written into its cells. For years, scientists have cataloged the changes in protein-coding genes and various non-coding RNAs that occur as we grow older. However, one class of molecules—circular RNAs originating from the genome of our cellular power plants, the mitochondria—has remained largely unexplored. A new research paper, titled “Aging-associated mitochondrial circular RNAs” published in Volume 18 of Aging-US by a multi-institutional team of researchers, provides the first detailed profile of these molecules and reveals a surprising link to cellular energy metabolism. The team's investigation demonstrates that a specific mitochondrial circular RNA, circMT-RNR2, is depleted in older individuals and plays a direct role in regulating the TCA cycle, the engine of cellular energy production. Full blog - https://aging-us.org/2026/03/mitochondrial-circular-rnas-new-players-in-human-aging/ Paper 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 – March 16, 2025 – Impact Journals (publisher of Aging-US, Oncotarget, Oncoscience, and Genes & Cancer), is pleased to announce its participation as an exhibitor at the American Association for Cancer Research (AACR) Annual Meeting 2026. The meeting will take place April 17–22, 2026, at the San Diego Convention Center in San Diego, CA. Conference attendees are warmly invited to visit Booth 3641 to meet members of the Impact Journals team, discover notable recent publications, and discuss opportunities for collaboration. The mission of Impact Journals is to maximize research impact through insightful peer review, eliminate borders between specialties by linking different fields of oncology and biomedical science, and foster the application of both basic and clinical science. This mission is grounded in a strong commitment to ethical standards and scientific integrity. At Impact Journals, evolving digital technologies, tools, and ideas are continually integrated into a robust scientific integrity process. The AACR Annual Meeting serves as a focal point for the global cancer research community, bringing together scientists, clinicians, healthcare professionals, survivors, patients, and advocates to share the latest advances in cancer science and medicine. From population science and prevention to cancer biology, translational and clinical studies, survivorship, and advocacy, the AACR Annual Meeting highlights the work of leading researchers from institutions around the world. To learn more about Impact Journals, please visit impactjournals.com. For media inquiries, email media@impactjournals.com.

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