GeroScience最新文献

{"title":"Nervonic acid and 15-epi-PGA1 mediate systemic mitochondrial dysfunction in AD dementia.","authors":"Stephanie Robyn Heimler,K Allison Amick,Jaclyn Bergstrom,Marcos Moliné,Gargi Mahapatra,Suzanne Craft,Anthony J A Molina","doi":"10.1007/s11357-025-01776-6","DOIUrl":"https://doi.org/10.1007/s11357-025-01776-6","url":null,"abstract":"Systemic mitochondrial dysfunction is apparent in the pathophysiology of Alzheimer's disease (AD). However, the factors driving bioenergetic decline remain unclear. This study utilized serum samples from older adults with normal cognition, mild cognitive impairment, and dementia to identify circulating molecules that can drive mitochondrial dysfunction in the context of AD. We used mass spectrometry to measure the abundance of lipid metabolites and applied tiered selection criteria to identify candidate \"mito-inhibitory\" molecules. These criteria were based on correlations with (1) in vitro bioenergetic effects of whole serum samples on naïve cells, (2) the bioenergetic capacity of blood cells from the serum donor, and (3) cognition, as measured by the modified mini-mental state exam. Mito-inhibitory lipid candidates were validated by examining their bioenergetic effects on neurons, myoblasts, and fibroblasts in vitro. Our results indicate that nervonic acid and 15-epi Prostaglandin A1 (15-epi-PGA1) are elevated in participants with dementia compared to those with normal cognition. Importantly, both metabolites inhibited mitochondrial function across multiple cell types in vitro. High resolution respirometric analyses reveal that inhibitory effects from lipid treatment occur via broad inhibition of the electron transfer system (ETS) with no change in overall mitochondrial content. This study provides insights into the mechanisms underlying systemic bioenergetic decline associated with AD dementia. The identification of circulating factors that drive mitochondrial bioenergetic decline may inform the development of mitochondrial therapeutics for AD.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"4 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144603987","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":"Age-dependent impairment of cardiac function and physical performance in male mice with diet-induced obesity.","authors":"Patricia Baumgarten,Justus Kamp,Niklas Hegemann,Stefanie Deubel,Nikolaus Berndt,Jana Grune,Wolfgang M Kuebler,Christopher L Axelrod,John P Kirwan,Annika Höhn,Sophie Heider,Christiane Ott,Tilman Grune","doi":"10.1007/s11357-025-01775-7","DOIUrl":"https://doi.org/10.1007/s11357-025-01775-7","url":null,"abstract":"Aging in the context of obesity exacerbates the risk of morbidity and mortality related to cardiovascular disease. However, the maladaptive responses in the heart that arise from prolonged obesity and the specific influence of biological age remain somewhat elusive. This study investigated the effects of diet-induced obesity (DIO) and aging on physical performance and cardiovascular function in mice. 22- and 76-week-old male C57BL/6J mice were randomized to 8 weeks of chow or high-fat diet. Body weight was assessed weekly. Body composition was measured at the beginning and the end of the diet treatment. Muscular and cardiac function were evaluated at the end intervention. Aged mice with DIO exhibited faster and greater body weight gain and fat mass accumulation, reduced running distance, and lower aerobic capacity. Aged HFD mice also exhibited increased cardiac lipid accumulation and cardiomyocyte hypertrophy, with no major morphological changes observed in skeletal muscle. Proteomic analysis revealed differential expression of heart proteins associated with metabolic function in young mice, which was not observed in aged mice with DIO. Subsequently, aged mice with DIO developed overt heart failure with reduced ejection fraction, while cardiac function was unaffected by DIO in young mice. In conclusion, young mice with DIO were protected against diet-induced cardiac dysfunction, whereas DIO in aged mice led to heart failure and impaired physical performance. The protective effects observed in younger mice appear to be explained by proteomic-level remodeling of the heart oriented to sustain cardiac function.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"22 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594223","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":"Kynurenine pathway dysregulation via loss of QPRT drives declines in activity and altered metabolism in mice.","authors":"Reyhan Westbrook,Vinal Menon,Joy Cagmat,Timothy Garrett,Robert Schwarcz,Jeremy Walston,Peter M Abadir,Tae Chung","doi":"10.1007/s11357-025-01735-1","DOIUrl":"https://doi.org/10.1007/s11357-025-01735-1","url":null,"abstract":"Chronic inflammatory pathway activation increases with age and is epidemiologically linked to multiple aging-related pathophysiological processes, phenotypes such as physical frailty and sarcopenia and early healthspan declines in aging organisms. Despite this, molecular mechanisms that directly connect chronic inflammation to these conditions remain poorly characterized. We hypothesize that chronic inflammation contributes to the development of age-related phenotypes by increasing the degradation of dietary tryptophan into multiple metabolites with unique physiological properties, called kynurenines, via the 'kynurenine pathway' (KP). To understand the impact of elevated KP metabolites on mammalian healthspan we utilized the quinolinate phosphoribosyltransferase knock-out (QPRT-/-) mouse which lacks the terminal enzyme of the KP and thus develops increased levels of downstream kynurenines. We tested the effects of this mutation on glucose handling, spontaneous motor activity, body composition and metabolism using indirect calorimetry, in male and female, young, middle aged and older mice. QPRT - / - mice had significantly altered levels of numerous KP metabolites and nicotinamide. Phenotypic characteristics varied in a sex-specific manner with decreased activity, lean mass and VO2, and impaired glucose clearance as early as 12 months seen in female QPRT-/- compared to age and sex-matched mice. Male QPRT-/- mice developed reduced lean mass by middle age and had altered respiration and food intake. This data indicates that KP dysregulation can drive declines in activity and alter metabolism in mammals and is a potential target to intervene on frailty and functional decline.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"21 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144594224","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":"Exploring motor unit and neuromuscular junction dysfunction in aging and sarcopenia: insights from electromyography in systematic review.","authors":"Can Cui,Yong Hu,Ronald Man Yeung Wong,Ning Zhang,Yuzhou Guan,Wing-Hoi Cheung","doi":"10.1007/s11357-025-01760-0","DOIUrl":"https://doi.org/10.1007/s11357-025-01760-0","url":null,"abstract":"The neuromuscular junction (NMJ) is a vital interface between motor neurons and muscle fibers, and alterations in its structure and function can substantially influence the onset and progression of sarcopenia. Electromyography (EMG) is a critical tool to assess motor unit and NMJ function, providing insights into neuromuscular activation patterns and the integrity of motor unit communication. However, its implications for aging and muscle performance during sarcopenia have not been fully discussed. Therefore, we conducted a systematic review using the PubMed, Embase, and Web of Science databases by employing relevant keywords. A total of 53 articles were included. This review explored the various alterations in the NMJ associated with aging, their functional implications, and potential interventions to mitigate these effects, highlighting the structural and functional alterations of the NMJ during aging and sarcopenia. Key findings include early NMJ transmission instability, motor unit loss and compensatory remodeling, and impaired neuromuscular activation preceding overt muscle atrophy and weakness. Notably, biomarkers such as C-terminal agrin fragment and neurofilament light chain, along with EMG-derived parameters (e.g., jitter, jiggle, MUNE), are sensitive indicators of NMJ deterioration. Both physical inactivity and hormonal changes (e.g., menopause) accelerate NMJ decline, while interventions such as resistance and endurance training, nutritional supplementation, and emerging gene therapies demonstrate potential to preserve or restore NMJ structure and function. In conclusion, this systematic review underscores the importance of NMJ dysfunction in aging and sarcopenia, advocating further research into diagnostic biomarkers and therapeutic strategies to enhance NMJ integrity. The interplay between aging, exercise, and NMJ function is complex and requires a nuanced approach to rehabilitation and exercise strategies tailored to the aging population. Future directions should prioritize the development of sensitive biomarkers, mechanistic studies of NMJ degeneration, and rigorous evaluation of multimodal interventions to mitigate neuromuscular decline and promote healthy aging.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"11 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578537","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":"Subjective memory concern, negative affect, and cortical microstructural integrity in community-dwelling middle-aged men.","authors":"Rongxiang Tang,Tyler R Bell,Jeremy A Elman,Chandra A Reynolds,Daniel E Gustavson,Olivia K Puckett,Matthew S Panizzon,Rosemary Toomey,Ruth McKenzie,Michael J Lyons,Donald J Hagler,Christine Fennema-Notestine,Lisa T Eyler,Anders M Dale,Carol E Franz,William S Kremen","doi":"10.1007/s11357-025-01778-4","DOIUrl":"https://doi.org/10.1007/s11357-025-01778-4","url":null,"abstract":"Concerns about memory often increase with age and have been suggested as a precursor to impending memory impairment or dementia. However, subjective memory concern (SMC) has also been shown to reflect an individual's trait-like tendency to worry about memory, which is more strongly linked to negative affect than to objective memory performance. Despite behavioral evidence supporting a trait-like dimension of SMC, its neuroanatomical underpinnings remain underexplored. In 477 community-dwelling dementia-free men (56-72 years old), we investigated the association between SMC and cortical mean diffusivity (cMD)-a diffusion MRI-based metric of gray matter microstructural integrity-generating a brain-wide map of their association. Self-report trait anxiety and depressive symptoms were collected, along with objective memory scores based on three neuropsychological tasks for which brain maps of their association with cMD were also generated. Finally, we conducted spatial correlational analyses to compare the spatial patterns of these brain association maps to assess whether there were significant spatial resemblances between each. We found that the gray matter integrity correlates of SMC spatially resembled those of depressive symptoms and trait anxiety but not those of objective memory. The spatial correspondences between gray matter integrity correlates of negative affect measures and SMC were significantly stronger than those between SMC and objective memory. Together, these results suggest a neuroanatomical basis of trait-like SMC, which should be distinguished from state-related SMC that may be a precursor of objective memory deficits in research and clinical settings.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"72 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578538","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":"The role of burnout prevention in promoting healthy aging: frameworks for the Semmelweis Study and Semmelweis-EUniWell Workplace Health Promotion Program.","authors":"Virág Zábó,Andrea Lehoczki,Annamária Buda,Péter Varga,Monika Fekete,Vince Fazekas-Pongor,Marianna Moizs,Giorgia Giovannetti,Yura Loscalzo,Marco Giannini,Beatrix Busse,Miklos Kellermayer,Iveta Nagyova,Yongjie Yon,Róza Ádány,Béla Merkely,György Purebl,Zoltan Ungvari","doi":"10.1007/s11357-025-01780-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01780-w","url":null,"abstract":"As the European Union undergoes a demographic shift toward an aging population, the rising prevalence of age-related diseases poses significant public health challenges. Across the EU, disparities in health indicators and life expectancies highlight the urgency of addressing factors that contribute to unhealthy aging. Burnout, characterized by emotional, physical, and mental exhaustion, has emerged as a critical determinant of healthy aging, with profound biological, psychological, and social implications. Burnout accelerates age-related decline, exacerbates health risks, and undermines overall well-being. This review explores the role of burnout in unhealthy aging, highlighting its underlying mechanisms and proposing actionable interventions. Workplace-based initiatives-such as the Caring University Model Program at Semmelweis University, which includes the Semmelweis Study and the Semmelweis-EUniWell Workplace Health Promotion Program developed within the European University for Well-Being (EUniWell) framework-offer a novel, integrated approach to embedding burnout prevention within broader public health strategies. By drawing on global best practices-including the Blue Zones model and Mediterranean lifestyle principles-and adapting them to diverse cultural contexts across Europe, these programs aim to foster resilience, reduce stress, and enhance workforce well-being. Addressing burnout as a critical determinant of health, these initiatives offer a scalable blueprint for promoting healthy aging and improving productivity throughout the EU. By incorporating burnout prevention into regional and national health policies, European countries can collectively extend healthspan, reduce healthcare costs, and enhance the quality of life for their aging populations.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"10 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578536","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":"Factor analysis of multimodal MRI, biofluid, and vascular biomarkers reveals latent constructs of brain health.","authors":"Ella Rowsthorn, Ming Ann Sim, William T O'Brien, Stuart J McDonald, Katherine Franks, Benjamin Sinclair, Trevor T-J Chong, Stephanie Yiallourou, Marina Cavuoto, Lucy Vivash, Terence J O'Brien, Xingfeng Shao, Danny J J Wang, Meng Law, Ian H Harding, Matthew P Pase","doi":"10.1007/s11357-025-01771-x","DOIUrl":"https://doi.org/10.1007/s11357-025-01771-x","url":null,"abstract":"<p><p>Individual imaging and fluid biomarkers provide insights into specific components of brain health, but integrated multimodal approaches are necessary to capture the complex, interrelated biological systems that contribute to brain homeostasis and neurodegenerative disease. Using data from the Brain and Cognitive Health (BACH) cohort study (N = 127; mean age = 67 years, 68% women), we performed an exploratory factor analysis to identify latent constructs of brain health. We included multimodal neurovascular imaging markers, brain atrophy metrics, plasma Alzheimer's disease (AD) biomarkers, and cardiovascular risk factors. Five constructs emerged: \"Brain & Vascular Health\" (greater hippocampal volume, basal ganglia enlarged perivascular spaces (ePVS), cerebral blood flow, and HDL cholesterol; lower ventricle volume and BMI), \"Structural Integrity\" (greater cortical thickness, fractional anisotropy, and basal ganglia ePVS), \"White Matter (WM) Fluid Dysregulation\" (greater WM ePVS and Free Water), \"AD Biomarkers\" (higher phosphorylated tau [pTau]181 and pTau217; lower amyloid-beta 42/40 ratio), and \"Neuronal Injury\" (higher glial fibrillary acidic protein and neurofilament light chain). All constructs were associated with age (β = - 0.70-0.39, p ≤ 0.014), except for WM Fluid Dysregulation (p > 0.05). Brain and Vascular Health and Structural Integrity (partial r = 0.305, p < 0.001) and AD biomarkers and neuronal injury (partial r = 0.248, p = 0.005) were positively correlated. Only Brain and Vascular Health was associated with global cognition (β = 0.27, SE = 0.13, p = 0.043). These findings provide a data-driven framework for examining distinct constructs underlying vascular health, fluid regulation, and neurodegenerative pathology. We demonstrate the utility of using multiple biomarkers to probe these biological systems, paving the way for future research to explore how these systems change across diverse neurodegenerative conditions.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144583737","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":"A physically and mentally active lifestyle relates to younger brain and cognitive age.","authors":"Niklas Behrenbruch,Svenja Schwarck,Beate Schumann-Werner,Eóin N Molloy,Berta Garcia-Garcia,Anne Hochkeppler,Larissa Fischer,Anna-Therese Büchel,Enise I Incesoy,Jose Bernal,Niklas Vockert,Patrick Müller,Gusalija Behnisch,Bárbara Morgado,Hermann Esselmann,Constanze I Seidenbecher,Björn H Schott,Henryk Barthel,Osama Sabri,Jens Wiltfang,Michael C Kreissl,Emrah Düzel,Anne Maass","doi":"10.1007/s11357-025-01764-w","DOIUrl":"https://doi.org/10.1007/s11357-025-01764-w","url":null,"abstract":"Resistance to age-related pathological changes (brain maintenance), including Alzheimer's disease, cerebrovascular disease, and neurodegeneration may promote cognitive resilience in aging. However, how lifestyle and health profiles relate to successful cognitive and brain aging remains poorly understood. In a novel, deeply phenotyped cohort of 211 cognitively unimpaired older adults (age = 71.0 ± 7.4 years, 46% female), we characterized principal components of lifestyle and health using questionnaire, fitness, and blood data. We estimated cognitive age gap (CAG) based on comprehensive neuropsychological data and brain age gap (BAG) based on brain-pathology markers, including plasma biomarkers of Alzheimer's pathology (pTau217 and Aβ1-42/Aβ1-40), MRI-based measures of white matter hyperintensities, perivascular spaces, and brain atrophy. Regression analyses tested how the observed lifestyle-health profiles were related to CAG and BAG. Seven principal components explained 49% of the variance in health and lifestyle. The second component, characterized by a mentally and physically active life and low cardiovascular risk, was associated with lower CAG (β = - 0.66, p < 0.001) and BAG (β = - 0.52, p = 0.003), reflecting a younger-than-expected brain and cognitive age, respectively. The association of an active lifestyle and lower CAG was partially mediated by BAG. Higher CAG was also associated with other lifestyle components characterized by low mental stimulation. APOE-ε4 carriers exhibited higher BAG. In conclusion, a lifestyle combining low cardiovascular risk, high mental engagement throughout life and high physical activity/fitness is jointly associated with less-than-expected brain pathology and better-than-expected cognitive performance, supporting its involvement in brain maintenance and cognitive resilience to aging.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"11 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144568480","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":"Dietary supplement use in longevity: evidence from 2,877 centenarians.","authors":"Jozo Grgic,Ajla Hodzic Kuerec,Brad J Schoenfeld","doi":"10.1007/s11357-025-01782-8","DOIUrl":"https://doi.org/10.1007/s11357-025-01782-8","url":null,"abstract":"Centenarians represent a population achieving extreme longevity. Despite growing interest in the role of dietary supplements in aging, there is limited research examining their use among centenarians. This study assessed the prevalence, duration, and frequency of dietary supplement use among centenarians in China. Data on self-reported supplement usage were sourced from the 2018 wave of the Chinese Longitudinal Healthy Longevity Survey. The analysis included 2,169 female and 708 male centenarians. Descriptive statistics were used to report prevalence, duration, and frequency of use, stratified by sex. Overall, 10.7% (95% confidence interval [CI] = 9.4%, 12.0%) of females and 12.3% (95% CI = 9.9%, 14.7%) of males reported using dietary supplements. The prevalence of calcium, protein, multivitamin, vitamin A/D, iron, zinc, and docosahexaenoic acid (DHA) use was between 6.5-7.3%, 3.7-5.8%, 2.8-3.0%, 1.9-2.1%, 1.2-1.4%, 1.2-1.3%, 0.4-0.7%, respectively. The frequency of use was typically reported as \"often\". The median duration of supplement use was from 2 to 10 years. Most supplement users (7.3-8.8%) consumed a single supplement. Approximately one in ten centenarians in China reported using dietary supplements. The most commonly consumed supplements were calcium, protein, and multivitamins, while DHA was the least commonly used. Participants who reported using supplements generally indicated regular consumption. The overall pattern of dietary supplement use was similar between females and males. Given the low overall prevalence of supplement use, this lifestyle practice appears to play a relatively minor role in the lives of centenarians in China.","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":"32 1","pages":""},"PeriodicalIF":5.6,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144578540","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":"Gene expression and co-expression heterogeneity patterns and biodemography analyses during the cell cycle encourage aging studies in archaea.","authors":"Yuping Dai, Miguel V Gomez-Raya-Vilanova, Jérôme Teulière, Mouhammad Toucourou, Eduardo Corel, Louis-Patrick Haraoui, Philippe Lopez, François-Joseph Lapointe, Claudio Franceschi, Annette Baudisch, Debashish Bhattacharya, Virginija Cvirkaite-Krupovic, Mart Krupovic, Eric Bapteste","doi":"10.1007/s11357-025-01769-5","DOIUrl":"https://doi.org/10.1007/s11357-025-01769-5","url":null,"abstract":"<p><p>One of the prokaryotic partners at the origin of eukaryotes was an archaeon, but do archaea age, and if so, how? Uncovering aging in Archaea might provide more general clues about cellular senescence and rejuvenation and their origins. To fill this knowledge gap, we focused on Saccharolobus islandicus, a model archaeon for which the cell cycle can be synchronized and controlled. We generated longitudinal transcriptomes of synchronized S. islandicus populations that capture typical expression and co-expression profiles associated with chronological aging. These experiments also allowed us to infer average cellular death rates during the cell cycle. Our results are compatible with general patterns of biological aging observed in single cells. However, at the population level, we observe a peak of mortality shortly after cell division in S. islandicus, which we interpret as \"negative\" demographic aging or ontogenescence, i.e., pre-reproductive mortality decline. To reconcile these observations, we propose a model of S. islandicus aging and rejuvenation. Our research constitutes a first step into the study of aging in archaea on the basis of gene expression, gene co-expression patterns during the cell cycle and biodemography analyses, and proposes a hypothetical new model to explore how cellular senescence and rejuvenation in eukaryotes may have prokaryotic roots. Alternative interpretations of our transcriptomic results however are possible, encouraging future experimental validation of aging in Archaea.</p>","PeriodicalId":12730,"journal":{"name":"GeroScience","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144564655","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}