Biogerontology最新文献

{"title":"Gasdermin, inflammatory, and heat-shock gene expression profiles in the naturally aged male mouse brain following propolis and dexpanthenol treatment.","authors":"Uğur Şahin","doi":"10.1007/s10522-026-10539-5","DOIUrl":"https://doi.org/10.1007/s10522-026-10539-5","url":null,"abstract":"<p><p>Aging is accompanied by alterations in inflammatory signaling, regulated cell-death pathways, and cellular stress responses in the brain. This study investigated the effects of propolis and dexpanthenol, administered individually or in combination, on gasdermin-related, inflammatory, and heat-shock gene expression in naturally aged male mice. Thirty-five male CD-1 mice were randomly allocated to five groups (n = 7/group): Young Control, Aged Control, Aged + Propolis, Aged + Dexpanthenol, and Aged + Propolis + Dexpanthenol. Propolis (200 mg/kg/day) and dexpanthenol (500 mg/kg/day) were administered for 14 days. Whole-brain mRNA expression of GSDMD, GSDME, GSDMC, TNF-α, IL-1β, HSP70, and HSP90 was evaluated by quantitative real-time PCR. Natural aging was associated with marked reductions in TNF-α, IL-1β, and HSP70 expression, whereas GSDMD, GSDME, GSDMC, and HSP90 were not significantly altered after correction for multiple comparisons. Propolis reduced GSDME and IL-1β expression while increasing GSDMC relative to aged controls. Dexpanthenol increased GSDMD and HSP70 expression, shifted TNF-α toward the young-control profile, and reduced HSP90 expression. Combined administration produced a distinct transcriptional profile characterized by pronounced increases in GSDMD, TNF-α, IL-1β, and HSP70 relative to aged controls. These findings indicate that propolis and dexpanthenol are associated with distinct, gene-specific transcriptional responses in the naturally aged brain rather than uniform changes across the inflammatory and gasdermin-related genes examined. Because the analyses were restricted to mRNA expression, the observed gasdermin transcriptional changes do not establish functional pyroptosis. The prominent HSP70 response further suggests that cellular stress adaptation and proteostasis may represent important components of these treatment-associated molecular changes.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149357099","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"From cave adaptation to ageing resilience: the Mexican cavefish Astyanax mexicanus.","authors":"Francisco Alejandro Lagunas-Rangel","doi":"10.1007/s10522-026-10540-y","DOIUrl":"https://doi.org/10.1007/s10522-026-10540-y","url":null,"abstract":"<p><p>The Mexican cavefish, Astyanax mexicanus, is a powerful evolutionary model for investigating how adaptation to extreme environments reshapes vertebrate physiology. Multiple cave populations have independently evolved under subterranean conditions, acquiring traits including insulin resistance, persistent hyperglycaemia, increased adiposity, altered sleep patterns, hypoxia tolerance and extensive metabolic reprogramming. Despite these differences, cavefish exhibit lifespans comparable to those of surface fish, while selected traits, including fertility and locomotor performance, appear to be better preserved with age. These observations challenge the assumption that persistent metabolic dysfunction necessarily entails accelerated functional decline and raise the possibility that cavefish have evolved mechanisms of ageing resilience. This narrative review examines evidence linking cave adaptation to biological processes relevant to ageing, focusing on nutrient sensing, lipid metabolism, mitochondrial function, redox homeostasis and immune regulation. Rather than eliminating metabolic stress, cave-associated adaptations may buffer some of its downstream consequences, preserving selected physiological functions. Evidence is evaluated within the framework of the hallmarks of ageing, considering genomic instability, telomere dynamics, deregulated nutrient sensing, mitochondrial dysfunction and chronic inflammation, while identifying major knowledge gaps regarding epigenetic alterations, loss of proteostasis, macroautophagy, cellular senescence, stem-cell exhaustion, altered intercellular communication and dysbiosis. The available evidence supports A. mexicanus as a comparative model for investigating how chronic environmental and metabolic stress can be uncoupled from selected aspects of functional decline. Distinguishing delayed ageing from enhanced tolerance or compensation in response to accumulated damage will be essential to establish the extent and mechanisms of ageing resilience in this species.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149340507","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Beyond age prediction: a task-oriented framework for evaluating molecular aging clocks.","authors":"Halimureti Simayijiang, Pei Ye, Liuli Zhang, Jiacheng Wu, Zhuo Li, Ying Long","doi":"10.1007/s10522-026-10535-9","DOIUrl":"https://doi.org/10.1007/s10522-026-10535-9","url":null,"abstract":"<p><p>Biological age estimation is increasingly used in aging research, but evaluation often relies too heavily on mean absolute error (MAE) against chronological age. We conducted a narrative review of major molecular aging clocks and propose an operational framework that links clock selection to the intended task. Applications are organized into four tasks: chronological-age estimation, age-independent deviation, future disease or mortality risk, and longitudinal monitoring of aging pace or intervention response. For each task, the framework specifies the target construct, output, preprocessing and confounding checks, validation metrics, and interpretation limits. A complementary four-layer model distinguishes relatively stable molecular measures, pace-of-aging measures, dynamic functional markers, and organ-specific vulnerability. Published examples illustrate why no single metric is sufficient: low age-prediction error does not establish clinical relevance, and strong risk association does not establish responsiveness to intervention. Aging clocks should therefore be evaluated as task-bound measurement tools, with explicit attention to calibration, discrimination, reliability, transportability, uncertainty, and incremental value. This framework is intended to support transparent model selection, reporting, and interpretation rather than designate a universally superior clock.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149294379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Investigating cognitive performance genetic architecture of cortical and subcortical brain tissues.","authors":"Mingyi Chen, Yuefang Chen, Bing Qin","doi":"10.1007/s10522-026-10534-w","DOIUrl":"https://doi.org/10.1007/s10522-026-10534-w","url":null,"abstract":"<p><p>Although the mechanisms underlying cognitive performance (CP) are increasingly understood, the genetic basis of the cerebral cortex and subcortical brain tissues and association with cognitive behaviors remain unclear. This study utilized the summarized expression quantitative trait loci (eQTL) data from the genotype-tissue expression (GTEx) v8 database along with CP data from genome-wide association studies (GWAS) on OpenGWAS. A total of 117 genes related to CP were identified, distributed across 9 brain regions: amygdala, anterior cingulate cortex, cortex, frontal cortex BA9, hippocampus, hypothalamus, accumbens, and caudate. Among them, 9 genes were present in at least 6 brain regions. Gene functional annotation revealed that these identified genes are primarily enriched in neuro-related pathways, associated with distinct brain cell types, and exhibit expression in peripheral tissues. The phenome-wide association study (PheWAS) highlighted the significance of genes related to CP for human health in multiple aspects, while the cognitive-behavioral association analysis revealed the association between 26 genes and specific cognitive behaviors. Furthermore, mendelian randomization (MR) analyses validated 9 genes (AFF3, TRIOBP, TYW5, CEP192, CHST10, WBP2NL, ANAPC4, GRK4, and LRPPRC) as biomarkers for CP. Notably, this study identified genes associated with CP in cortical and subcortical brain tissues and demonstrated that these genes are significantly associated with changes in cognitive behaviors. This crucial discovery offers new insights into the prevention and control of early cognitive deterioration in European-ancestry populations.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261836","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dissecting the shared genetic architecture of adipose tissue aging and aging-related lipid-metabolic dysfunction: a multivariate genomic analysis.","authors":"Mingkai Li, Yunshu Yao, Yafei Zhao, Qinfei Guo, Chenyang Li, Chenhui Lv, Boqian Zhang, Jinxin Li, Haifeng Zhao","doi":"10.1007/s10522-026-10537-7","DOIUrl":"https://doi.org/10.1007/s10522-026-10537-7","url":null,"abstract":"<p><p>Adipose tissue aging is increasingly recognized as a systemic process involving altered fat distribution, ectopic lipid deposition, and metabolic dysfunction, yet its shared genetic architecture remains incompletely characterized. In this study, we constructed a latent multivariate genetic phenotype of adipose tissue aging by integrating genome-wide association summary statistics for seven adipose- and metabolism-related traits, including visceral adipose tissue volume, abdominal subcutaneous adipose tissue volume, thigh subcutaneous adipose tissue volume, liver proton density fat fraction, fasting insulin, adiponectin, and leptin. Using Genomic Structural Equation Modelling, we derived a latent phenotype termed mvAdiposeAge and further characterized its genetic and biological relevance through genome-wide association analysis, FUMA-based functional annotation, MAGMA gene-level analysis, transcriptome-wide association analysis, expression fine-mapping, pathway and tissue enrichment analyses, and Mendelian randomization. The Genomic SEM model supported a shared genetic dimension linking adipose distribution, ectopic lipid accumulation, and adipose-related metabolic traits. Genome-wide analysis identified a prominent signal at chromosome 16q12.2, with rs1421085 in the FTO region emerging as the lead variant. MAGMA identified 49 FDR-significant genes, while transcriptome-wide analysis prioritized 11 genes, with FOCUS fine-mapping highlighting expression-mediated signals involving FTO, RPGRIP1L, and AKTIP. Functional enrichment implicated neurotrophin signalling, synaptic organization, cAMP signalling, immune and phagocytic processes, endocrine regulation, and metabolic pathways, with tissue enrichment suggesting prominent brain-region-specific signals. Mendelian randomization further supported positive associations of adiposity-related traits with mvAdiposeAge and an inverse association with cognitive performance. These findings highlight mvAdiposeAge as a latent genetic factor capturing shared genetic variation across adipose-related phenotypes relevant to aging and provide a framework for further investigating their systemic biological associations.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ginsenoside Rg1 promotes mitophagy and delays aging through the DAF-16 in Caenorhabditis elegans.","authors":"Xiang Li, Hui Shang, Nana Chen, Tenglong Ma, Ding Lu, Ruobing Liu, Pingxuan Fan, Shaopu Li, Songtao Bie","doi":"10.1007/s10522-026-10536-8","DOIUrl":"https://doi.org/10.1007/s10522-026-10536-8","url":null,"abstract":"<p><p>Ginsenoside Rg1, the main active component of Panax ginseng, has been shown to improve mitochondrial function and delay cell aging by regulating chaperone-mediated mitophagy. However, how Rg1 works in Caenorhabditis elegans is still unclear. In this study, C. elegans was used as a model to study how Rg1 regulates autophagy and mitochondrial function, and to understand its anti-aging mechanism. The results showed that Rg1 treatment significantly kept cells alive and maintained muscle shape in aged C. elegans, and effectively extended their lifespan. Further studies found that Rg1 improved mitochondrial function by activating mitophagy, which helped the C. elegans better resist oxidative stress. In addition, by combining RNA sequencing and bioinformatics analysis, the transcription factor daf-16 was identified as a key target of Rg1. Experiments using daf-16 knockout strains confirmed that Rg1 produced its anti-aging effects through the daf-16 pathway, in which the activation of mitophagy and the improvement of antioxidant ability were both mediated by daf-16. In conclusion, this study shows that Rg1 slows aging in C. elegans through a daf-16-mediated mitophagy pathway, providing experimental support for the study and use of natural products in anti-aging research.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pharmacological downregulation of Fetuin-A attenuates TLR4-mediated neuroinflammation in aged rats with minimal hepatic encephalopathy.","authors":"Vishal Vikram Singh, Priyanka Thakur, Shambhu Kumar Prasad, Arup Acharjee, Papia Acharjee","doi":"10.1007/s10522-026-10533-x","DOIUrl":"https://doi.org/10.1007/s10522-026-10533-x","url":null,"abstract":"<p><p>Minimal hepatic encephalopathy (MHE) is a neurological complication associated with chronic liver disease characterized by subtle cognitive impairment and neuroinflammation, particularly in the aging population. However, the molecular mechanisms underlying age-associated MHE remain poorly understood. The present study investigated the role of Fetuin-A-mediated neuroinflammation and its potential as a therapeutic target in the management of MHE in old rats using pioglitazone in a thioacetamide (TAA)-induced MHE model in aged rats. Old male rats were administered TAA (50 mg/kg) for 14 days to induce MHE, followed by pioglitazone treatment (3 mg/kg) for 7 days. Western blot and immunofluorescence analyses revealed elevated hippocampal Fetuin-A expression in MHE rats, accompanied by activation of the TLR4/MyD88/NF-κB signaling pathway and increased inflammatory cytokines (IL-6 and TNF-α). Pioglitazone treatment significantly reduced Fetuin-A expression and was accompanied by reduced TLR4, MyD88 and nuclear NF-κB expression, and by decreased astrocyte activation Furthermore, histological and Golgi-Cox analyses demonstrated restoration of neuronal density, dendritic arborization, and spine density in the hippocampus of pioglitazone-treated old MHE rats. Behavioral analyses further confirmed the molecular and histological findings. Thus, elevated hippocampal Fetuin-A is associated with TLR4/MyD88/NF-κB activation in aged MHE rats, and its pharmacological reduction by pioglitazone is accompanied by reduced neuroinflammation, restored hippocampal cytoarchitecture and recovered recognition memory. A causal role for Fetuin-A remains to be established by direct perturbation.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149261793","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysergic acid diethylamide extends lifespan in Caenorhabditis elegans.","authors":"Beatriz S Carrilho, Aline Teixeira Duarte Silva, Isabelle Martins, Ariane Moura, Manuela Vilas, Matheus Antonio V C Ventura, Francisco Moll, Hugo Aguilaniu, Ivan Domith, Stevens Rehen","doi":"10.1007/s10522-026-10521-1","DOIUrl":"10.1007/s10522-026-10521-1","url":null,"abstract":"<p><p>Aging is modulated by conserved nutrient-sensing pathways that integrate metabolic cues to regulate growth, stress resilience, and lifespan. Caloric restriction (CR) extends longevity across species, motivating the search for compounds that engage related physiology. Lysergic acid diethylamide (LSD), a classic serotonergic psychedelic with emerging therapeutic applications, remains unexplored in the context of aging. Here we show that chronic exposure to nanomolar LSD extends lifespan in Caenorhabditis elegans by up to 17.6% at the 25% survival timepoint, and reduces age-associated lipofuscin accumulation. This response involves serotonergic GPCR signaling: LSD failed to extend lifespan in ser-1 and ser-5 mutants and shortened lifespan in ser-4 and ser-7 mutants, yet remained effective, although with reduced magnitude, in tph-1 animals deficient in serotonin synthesis, indicating that endogenous serotonin production is not strictly required. LSD also elicited phenotypes that overlap with CR, including reduced reproductive output, smaller body size, delayed vulval development, and time-dependent remodeling of lipid stores and PHA-4 levels, while adult food-consumption assays detected no reduction in feeding under the conditions tested. Notably, the lifespan benefit was absent in eat-2 mutants and was lost under bacterial dilution, where LSD instead shortened lifespan, indicating that nutritional context shapes the response. Transient exposure during early adulthood was sufficient to extend lifespan. Together, these findings identify LSD as a tool to investigate how serotonergic signaling interfaces with conserved longevity-related pathways.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13690901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242717","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resveratroloside alleviates senescence-associated phenotypes in vitro through the coordinated regulation of mitochondrial function and chromatin structure.","authors":"Jee Hee Yoon, Ye Hyang Kim, Duyeol Kim, Eun Young Jeong, So Hun Lee, Ha Yeon Kim, Ji Ho Park, Moon Kyoung So, Yoo Jin Lee, Minseon Kim, Jihyun Song, Sehui Lim, Youngjoo Byun, Song Seok Shin, Joon Tae Park","doi":"10.1007/s10522-026-10532-y","DOIUrl":"https://doi.org/10.1007/s10522-026-10532-y","url":null,"abstract":"<p><p>Cellular senescence is characterized by coordinated disruptions in mitochondrial function and epigenetic regulation, with perturbation of the mitochondria-chromatin axis emerging as a central hallmark of this process. Resveratrol (RSV) has been extensively investigated as a modulator of this axis; however, its clinical utility is constrained by dose-dependent cytotoxicity. Here, we evaluated the safety profile and anti-aging potential of resveratrol glucoside (R-glc), a glucosylated derivative of RSV. R-glc exhibited markedly reduced cytotoxicity compared to RSV and effectively attenuated multiple senescence-associated phenotypes at low concentrations. Mechanistically, R-glc enhanced mitochondrial function, as evidenced by increased oxidative phosphorylation and reduced glycolytic dependence. At the epigenetic level, R-glc upregulated the NAD⁺-dependent deacetylase SIRT6 and decreased histone H3 lysine 9 (H3K9) acetylation, indicating improved chromatin stability. Taken together, these findings identify R-glc as a safer and functionally effective modulator of the mitochondria-chromatin axis, supporting its potential as a clinically applicable intervention for age-related functional decline.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149242665","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Environmental variability versus extrinsic mortality as correlates of mammalian lifespan: a pre-specified comparative analysis with phylogenetic and deep-time evidence.","authors":"Daicun Li","doi":"10.1007/s10522-026-10531-z","DOIUrl":"https://doi.org/10.1007/s10522-026-10531-z","url":null,"abstract":"&lt;p&gt;&lt;p&gt;What explains the large variation in lifespan across species? I examine an information-turnover proposition-that ancestral environmental variability should shorten captive lifespan after controlling for body mass, temperature and extrinsic mortality (P1), with a possible lineage-fate interaction (P2)-against the classical extrinsic-mortality prediction that safer niches permit longer life. I state the decision rules in advance rather than register a third-party protocol. Integrating AnAge (4,219 records), PanTHERIA, WorldClim/CHELSA climate and a 4,100-species mammal phylogeny with Pagel's-λ phylogenetic generalized least squares (PGLS), together with Paleobiology Database fossils across two mass extinctions, the lifespan-mass scaling reproduces (slopes 0.158 mammals, 0.212 birds; P &lt; 10⁻&lt;sup&gt;140&lt;/sup&gt;). P1 is not supported under the most conservative specifications: weak proxy signals attenuate or reverse at λ = 1 and under family fixed effects, and the set of analyses is best read as overlapping sensitivity and robustness checks rather than independent falsifications; equivalence intervals for the climate coefficients exclude large (arboreality-sized) effects but not small ones. A basal-metabolic-rate correlate likewise dissolves at λ = 1. Turning the same pipeline to niche safety, flight, arboreality, aquatic life and hibernation carry positive mass-corrected coefficients in raw and maximum-likelihood-λ contrasts; at λ = 1 in a joint model (n = 652) only multiply-origin arboreality is significant (b = + 0.106 dex, 95% CI 0.065-0.147, P = 5.8 × 10&lt;sup&gt;-7&lt;/sup&gt;), whereas flight and aquatic life are inconclusive with wide confidence intervals. Ancestral reconstruction recovers dozens of independent arboreal gains (42 by parsimony; 45-50 by maximum-likelihood; stochastic-mapping median 70-81, 95% range ≈ 57-94) versus one to a few for flight or aquatic life. Bivalve geographic breadth is associated with survival across the K-Pg and end-Permian extinctions, although the effect weakens after controlling for sampling completeness and is a genus-level extinction phenomenon rather than an individual-lifespan mechanism. Turtles live ≈ 1.8 × longer than same-mass squamates (turtle-squamate comparison n = 179, P = 8 × 10&lt;sup&gt;-8&lt;/sup&gt;). Human lifespan is an extreme outlier on the scaling plane. The comparative evidence is therefore most consistent with a strong association between extrinsic-mortality regime (niche safety) and lifespan, and with no detectable independent role for environmental fluctuation rate at the effect sizes this study could resolve; I report where inference is inconclusive rather than claim a null effect or a decisive causal setting. The focal analyses comprise 977 mammals and 1,063 birds for the scaling law, 798 species with climate data, 878 species with trait contrasts, 652 species in the joint phylogenetic model, and 349 species with basal metabolic rate (298 in the tree-matched model); each result reports its own sample siz","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 6","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149226996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}