GeroScience最新文献

{"title":"Insomnia accelerates the epigenetic clocks in older adults","authors":"Nadia Alejandra Rivero-Segura, Julian Daniel Rodriguez Cuartas, Paola Garcia-delaTorre, Sergio Sanchez-Garcia, Ricardo Ramirez-Aldana, Juan Carlos Gomez-Verjan","doi":"10.1007/s11357-025-01608-7","DOIUrl":"https://doi.org/10.1007/s11357-025-01608-7","url":null,"abstract":"<p>Insomnia is a common sleep disorder characterized mainly by poor sleep quality and insufficient sleep duration. It affects a significant proportion of the global population and is correlated with physical and mental consequences such as cognitive decline, anxiety, chronic fatigue, poor concentration, and memory impairment. Interestingly, it is also linked to ageing and age-related diseases (cardiovascular, metabolic, and neurodegenerative). On the other hand, as we age, DNA methylation patterns undergo significant changes. These have been used to develop the so-called epigenetic clocks that estimate the biological age linked to the environment and the risk of diseases. Few studies have evaluated the association between insomnia and epigenetic clocks, providing insight into the role of insomnia in ageing acceleration. Therefore, in the present study, we carried out an epigenetic analysis by using Illumina EPICv.2 array on 63 older adults (&gt; 60 years old, <i>n</i> = 33 with insomnia vs. <i>n</i> = 30 control) to evaluate the relation between insomnia and epigenetic ages (HorvathAGE, HannumAGE, PhenoAGE, SkinBloodClock, GrimAGE, DunedinPACE, DNAmTL). As a result, we found an increased acceleration and correlation between GrimAGE and SkinBloodClock and a significant reduction in the DNAmTL in individuals with insomnia. An EWAS analysis showed a global pattern of hypomethylation and an enrichment of several proteostasis and oxidative pathways. In conclusion, our results suggest that insomnia increases GrimAGE and SkinBloodClock acceleration and may be participating in telomere shortening. Additionally, changes in DNA methylation patterns induced by insomnia impact proteostasis and oxidative stress.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"69 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex differences in cognitive performance persist into your 80s","authors":"Ross Julian, Stephanie Fröhlich, Katrin Müller, Melanie Dammhahn, Claudia Voelcker-Rehage","doi":"10.1007/s11357-025-01585-x","DOIUrl":"https://doi.org/10.1007/s11357-025-01585-x","url":null,"abstract":"<h3 data-test=\"abstract-sub-heading\">Background</h3><p>Sex differences in cognitive performance have been extensively documented. Understanding the underlying factors contributing to sex differences in older adults is imperative to promote healthy cognitive aging. Sex hormones, estrogens, and testosterone have been suggested to be associated with cognition. Nevertheless, there is a scarcity of studies investigating the sex difference in cognitive performance and the contribution of gonadal hormones in older adults. Hence, the current study aimed to investigate sex differences in cognitive performance and elucidate the association between gonadal hormones and cognitive performance in 80+ -year-olds.</p><h3 data-test=\"abstract-sub-heading\">Methods</h3><p>Using confirmatory factor analysis in a sample of 131 older adults (aged 80 to 92 years), 17 cognitive performance measures were divided into two cognitive components: executive functioning and memory. Subsequently, mediation analyses were conducted to determine the direct effect of sex and the indirect effect mediated by gonadal hormones on executive functioning and memory.</p><h3 data-test=\"abstract-sub-heading\">Results</h3><p>Females outperformed males in executive functioning and memory. However, gonadal hormones did not mediate the sex effect on cognitive performance. Estrogen levels significantly predicted executive functioning but not memory. Testosterone levels did neither predict executive functioning nor memory.</p><h3 data-test=\"abstract-sub-heading\">Conclusion</h3><p>Our study confirms enduring sex differences in memory and executive function, even among individuals aged 80 and above. Current gonadal hormone levels do not mediate these differences. While estrogen may predict executive function, its influence does not explain the sex differences. These findings underscore the complex nature of cognitive disparities between sexes in older age, warranting further investigation into underlying mechanisms.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"39 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frailty incidence by diabetes treatment regimens in older adults with diabetes mellitus in the ASPirin in Reducing Events in the Elderly Study","authors":"Sara E. Espinoza, Jonathan C. Broder, Rory Wolfe, Michael E. Ernst, Raj C. Shah, Suzanne G. Orchard, Robyn L. Woods, Joanne Ryan, Anne Murray","doi":"10.1007/s11357-025-01598-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01598-6","url":null,"abstract":"<p>Diabetes mellitus is a major risk factor for frailty in older adults, and studies suggest that frailty risk may differ by diabetes treatment regimen. To investigate the association between diabetes medication use and frailty, we conducted an observational cohort analysis of older adults with diabetes enrolled in the ASPirin in Reducing Events in the Elderly (ASPREE) study. Diabetes at baseline (<i>N</i> = 2045) was defined as self-reported diabetes, fasting blood glucose levels &gt; 125 mg/dL, or use of diabetes medication. Diabetes medication exposure at baseline was categorized as use of metformin only (monotherapy) (<i>N</i> = 545), metformin combined with other diabetes medications (<i>N</i> = 420), other diabetes medications only (<i>N</i> = 200), or no diabetes medications (<i>N</i> = 880). Frailty was defined using a modified Fried frailty phenotype (presence of ≥ 3 of 5 criteria) and a deficit accumulation frailty index (FI, score &gt; 0.21/1.00). Mixed effects ordinal logistic regression models revealed the odds of frailty at baseline were highest for the other diabetes medications only group, but this difference remained consistent over follow-up. After adjustment for covariates, including baseline pre-frailty, no differences in the rates of Fried or FI frailty were observed among the diabetes medication exposure groups. These findings suggest that diabetes medication exposure in older adults with diabetes does not directly impact frailty risk.</p><h3 data-test=\"abstract-sub-heading\">Graphical abstract</h3>\u0000","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"24 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143640840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Machine vision-based frailty assessment for genetically diverse mice","authors":"Gautam S. Sabnis, Gary A. Churchill, Vivek Kumar","doi":"10.1007/s11357-025-01583-z","DOIUrl":"https://doi.org/10.1007/s11357-025-01583-z","url":null,"abstract":"<p>Frailty indexes (FIs) capture health status in humans and model organisms. To accelerate our understanding of biological aging and carry out scalable interventional studies, high-throughput approaches are necessary. We previously introduced a machine vision-based visual frailty index (vFI) that uses mouse behavior in the open field to assess frailty using C57BL/6J (B6J) data. Aging trajectories are highly genetic and are frequently modeled in genetically diverse animals. In order to extend the vFI to genetically diverse mouse populations, we collect frailty and behavior data on a large cohort of aged Diversity Outbred (DO) mice. Combined with previous data, this represents one of the largest video-based aging behavior datasets to date. Using these data, we build accurate predictive models of frailty, chronological age, and even the proportion of life lived. The extension of automated and objective frailty assessment tools to genetically diverse mice will enable better modeling of aging mechanisms and enable high-throughput interventional aging studies.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"5 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635152","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing the gut microbiota composition in older adults: connections to physical activity and healthy ageing","authors":"Catarina Ramos, Daniele Magistro, Gemma E. Walton, Anya Whitham, Nicola Camp, Carlos Poveda, Glenn R. Gibson, John Hough, Will Kinnear, Kirsty Hunter","doi":"10.1007/s11357-025-01605-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01605-w","url":null,"abstract":"<p>The composition and functionality of the gut microbiota (GM) changes throughout the life course. As we move into older age, it starts to shift towards a less healthy one, which may lead to an imbalance in the GM community. Strategies that can reverse age-related dysbiosis are an important part of healthy aging. Little is known about the GM composition of older adults with different physical activity (PA) levels and whether it might contribute to healthy ageing. The aim of this study was to compare the GM composition of older adults with different PA levels and assess if it is associated with healthy ageing. 101 participants aged between 65–85 years undertook anthropometric measures, a 6-min walking test, wore an accelerometer for 7 days and provided a faecal sample. Faecal GM composition was analysed using 16S rRNA sequencing. We found that those who fulfilled the WHO/UK PA recommendations had higher relative abundance of several health-related bacteria such as <i>Lactobacillus, F. prausnitzii</i> and <i>Roseburia intestinalis</i> and lower abundance of disease-associated bacteria such as <i>D.piger</i> or Enterobacterales when compared to those who did not reach PA recommendations. These findings suggest that PA might improve the GM composition and has the potential to, at least partially, revert age-associated dysbiosis and promote healthy ageing.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"33 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Epigenetic age acceleration and mortality risk prediction in US adults","authors":"Angelico Mendy, Tesfaye B. Mersha","doi":"10.1007/s11357-025-01604-x","DOIUrl":"https://doi.org/10.1007/s11357-025-01604-x","url":null,"abstract":"<p>Epigenetic clocks have emerged as novel measures of biological aging and potential predictors of mortality. We examined all-cause, cardiovascular, and cancer mortality prediction by epigenetic age acceleration (EAA) estimated using different epigenetic clocks. Among 2105 participants to the 1999–2002 National Health and Nutrition Examination Survey aged ≥ 50 years old and followed for mortality through 2019, we calculated EAAs from the residuals of nine epigenetic clocks regressed on chronological age. We assessed the association of EAAs and pace of aging with mortality adjusting for covariates. During 17.5 years of median follow-up, 998 deaths occurred, including 272 from cardiovascular disease and 209 from cancer. Overall mortality was most significantly predicted by Grim EAA (<i>P</i> &lt; 0.0001) followed by Hannum (<i>P</i> = 0.005), Pheno (<i>P</i> = 0.004), Horvath (<i>P</i> = 0.03), and Vidal-Bralo (<i>P</i> = 0.04) EAAs. Grim EAA predicted cardiovascular mortality (<i>P</i> &lt; 0.0001), whereas Hannum (<i>P</i> = 0.006), Horvath (<i>P</i> = 0.009), and Grim (<i>P</i> = 0.01) EAAs predicted cancer mortality. Overall mortality prediction differed by race/ethnicity between non-Hispanic White and White participants for Horvath (<i>P</i>_interaction = 0.048), Hannum (<i>P</i>_interaction = 0.01), and Grim (<i>P</i>_interaction = 0.04) EAAs. Hannum prediction of cancer mortality also differed between the two races/ethnicities (<i>P</i>_interaction = 0.007). Despite being predictive in non-Hispanic White participants, Horvath (<i>P</i> = 0.75), Hannum (<i>P</i> = 0.84), and Grim (<i>P</i> = 0.10) EAAs failed to predict overall mortality in Hispanic participants, and Hannum EAA was not associated with cancer mortality in Hispanic participants (<i>P</i> = 0.18). In a US representative sample, Horvath, Hannum, SkinBlood, Pheno, Vidal-Bralo, and Grim EAAs as well as pace of aging predict mortality. Howbeit, Horvath, Hannum, and Grim EAAs were less predictive in Hispanic participants.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"19 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635159","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-Monothiopomalidomide, a new immunomodulatory imide drug (IMiD), blunts inflammation and mitigates ischemic stroke in the rat","authors":"Kai-Yun Chen, Shih-Chang Hsueh, Pathik Parekh, Buyandelger Batsaikhan, David Tweedie, Weiming Luo, Chirag Patel, Yung-Hsiao Chiang, Nicholas Bambakidis, Barry J. Hoffer, Chi-Zong Huang, Seong-Jin Yu, Kuo-Jen Wu, Yun Wang, Eunji Hong, Dong Seok Kim, Nigel H. Greig","doi":"10.1007/s11357-025-01573-1","DOIUrl":"https://doi.org/10.1007/s11357-025-01573-1","url":null,"abstract":"<p>An overactive neuroinflammatory response is often evident in the elderly and is a significant contributor to brain tissue damage following acute ischemic stroke. Such an inflammatory response is largely mediated by microglial cells and peripheral blood mononuclear cells (PBMCs). Classical anti-inflammatory agents have not proved clinically effective in mitigating the impact of ischemic stroke but have highlighted targets for new drug development, in particular excessive proinflammatory cytokine release. The immunomodulatory imide drug (IMiD) class has shown potential in reducing neuroinflammation and switching microglial phenotypic expression away from a proinflammatory to a regenerative anti-inflammatory one. 3-Monothiopomalidomide (3-MP), a new IMiD, has a brain/plasma concentration ratio of 0.5 to 0.6, an oral bioavailability of 38.5%, and a monophasic disappearance of half-life 3.2 h following oral administration. 3-MP pretreatment mitigates lipopolysaccharide (LPS)-induced inflammation in cellular human PBMCs and, in rat studies, 3-MP pretreatment lowers proinflammatory cytokine levels in the conditioned media and in plasma and the brain, respectively. Administered systemically to rats challenged with middle cerebral artery occlusion (MCAo) and reperfusion, 3-MP post-MCAo treatment reduced infarction volume; improved body asymmetry, a behavioral measure of stroke impact; and lowered inflammation. In summary, 3-MP exerted neuroprotective effects via anti-inflammatory actions against MCAo-induced ischemic injury and represents a therapeutic that warrants further investigation as a treatment for brain damage and related disorders associated with excessive inflammation.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"16 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143635188","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Micro-gyms as a catalyst for healthy aging in university and healthcare settings: applications for the Semmelweis-EUniWell Workplace Health Promotion Model Program","authors":"Noémi Mózes, Dorottya Árva, David Major, Mónika Fekete, Norbert Dósa, Andrea Lehoczki, Péter Varga, Kata Pártos, Wei Yi Hung, Giorgia Giovannetti, Daniele Vignoli, Beatrix Busse, Mariann Moizs, Iveta Nagyova, Yongjie Yon, György Purebl, Béla Merkely, Róza Ádány, Vince Fazekas-Pongor, Zoltán Ungvári","doi":"10.1007/s11357-025-01595-9","DOIUrl":"https://doi.org/10.1007/s11357-025-01595-9","url":null,"abstract":"<p>Europe is experiencing a significant demographic shift, with aging populations posing economic and social challenges due to increased healthcare costs and a higher prevalence of age-related diseases. Hungary, in particular, faces these challenges acutely due to higher morbidity and mortality rates from a range of chronic age-related diseases and behavioral risk factors. Addressing these issues requires innovative approaches to promote healthy aging. Semmelweis University, the largest healthcare provider and leading health sciences university in the region, is developing a comprehensive healthy aging program. A critical pillar of this program is the Semmelweis-EUniWell Workplace Health Promotion Model Program, a pioneering initiative aimed at tackling unhealthy aging within Hungary’s workforce by leveraging the workplace as a platform for health promotion. Central to this program’s goal of combating sedentary lifestyles—a significant contributor to age-related health issues—is the innovative use of micro-gyms and motivational interviewing. Micro-gyms, with their compact size and accessibility, provide convenient exercise opportunities, while motivational interviewing fosters intrinsic motivation and personalized counseling to encourage sustained physical activity. Through concerted efforts and innovative approaches, including the implementation of micro-gyms, the Semmelweis-EUniWell Workplace Health Promotion Model Program aims to set a benchmark for workplace health promotion, fostering a healthier and more resilient aging population in Hungary. This program not only enhances the well-being of employees at Semmelweis University and its EUniWell partner institutions but also catalyzes broader transformations in workplace health promotion and healthy aging nationwide.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"87 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627563","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Salutary effects of transdermal curcumin on multiple indices of health span in rodent models of normal aging and hypertension","authors":"Kai Mao, Ruixuan Wang, Kateryna Karpoff, Daniel Kerr, Probal Banerjee, Joel M. Friedman, Derek M. Huffman","doi":"10.1007/s11357-025-01607-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01607-8","url":null,"abstract":"<p>Geroscience has helped to usher in a new and exciting era of aging drug development and evaluation of novel and repurposed agents, as well as natural compounds purported to target one or more aging hallmarks. Among the latter, curcumin has long been pursued as a promising strategy but has failed to provide convincing evidence in human trials. Oral intake is the typical route of administration tested for the vast majority of gerotherapeutic candidates, including curcumin, but efficacy is dependent upon good oral bioavailability and pharmacokinetics. However, unlike FDA-approved oral medications, many natural compounds, such as curcumin, have poor oral bioavailability, which may explain their limited success in translation. To overcome these inherent limitations, we tested a novel solvent-based formulation of concentrated curcumin (VASCEPTOR®), developed for effective skin penetration and delivery of high amounts of bioactive curcuminoids directly to the circulation on aging and age-related conditions. We demonstrate that short-term topical treatment (7.5 mg per dose) with VASCEPTOR® twice per week can improve both vascular health in a rat model of hypertension, while a late-life intervention in aged mice improves multiple indices of health span, including improved exercise tolerance, motor coordination, diastolic function (<i>p</i> &lt; 0.05), a reduction in frailty status (<i>p</i> &lt; 0.05) and expression of some age-related markers in tissues, particular heart and kidney. Thus, these data suggest that the therapeutic potential of curcumin can potentially be dramatically enhanced by topical delivery and, along with other promising candidates, should be prioritized for further development, testing and deployment to potentially target some manifestations of aging in humans.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"17 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143627796","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Topoisomerase inhibitor amonafide enhances defense responses to promote longevity in C. elegans","authors":"Iman Man Hu, Ana Serna, Stacia Everts, Lale Güngördü, Bauke V. Schomakers, Ellen A. A. Nollen, Arwen W. Gao, Riekelt H. Houtkooper, Georges E. Janssens","doi":"10.1007/s11357-025-01599-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01599-5","url":null,"abstract":"<p>Aging is a major risk factor for disease, and developing effective pharmaceutical interventions to improve healthspan and promote longevity has become a high priority for society. One of the molecular pathways related to longevity in various model organisms revolves around lowering AKT1 levels. This prompted our in silico drug screen for small molecules capable of mimicking the transcriptional effects of <i>AKT1</i> knockdown. We found topoisomerase inhibitors as a top candidate longevity-drug class. Evaluating multiple compounds from this class in <i>C. elegans</i> revealed that the topoisomerase inhibitor amonafide has the greatest benefit on healthspan and lifespan. Intriguingly, the longevity effect of amonafide was not solely dependent on <i>DAF-16/FOXO</i>, the canonical pathway for lifespan extension via <i>AKT1</i> inhibition. We performed RNA-seq on amonafide-treated worms and revealed a more youthful transcriptional signature, including the activation of diverse molecular and cellular defense pathways. We found the mitochondrial unfolded protein response (UPR^mt) regulator <i>afts-1</i> to be crucial for both improved healthspan and extended lifespan upon amonafide treatment. Moreover, healthspan was partially dependent on the immune response transcription factor <i>zip-2</i> and the integrated stress response transcription factor <i>atf-4</i>. We further examined the potential of amonafide in age-related disease. Treating a <i>C. elegans</i> model for Parkinson’s disease with amonafide improved mobility. In conclusion, we identified amonafide as a novel geroprotector, which activates mitochondrial-, pathogen-, and xenobiotic-associated defense responses that—though more studies are needed—may serve as a candidate for Parkinson’s disease therapy.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"213 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143618416","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}