Aging-US

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

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

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

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

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

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

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

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

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

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