Biogerontology最新文献

{"title":"Sex-stratified immune patterns across the canine lifespan and short-term responses to geroprotective interventions.","authors":"Meiling Lai, Fengge Xu, Yingxia Xu, Albert Mironenkov, Yi Jin, Shengxiang Zhang, Jianhong Pan, Ming Li, Baichuan Deng, Jian-Kang Zhu, Yu-Xuan Lyu","doi":"10.1007/s10522-026-10518-w","DOIUrl":"https://doi.org/10.1007/s10522-026-10518-w","url":null,"abstract":"<p><p>Canine models are invaluable for translational geroscience, but natural sex-associated immune aging remains under investigated. Here, we characterize the age-associated hematologic and serum cytokine profiles in a controlled cross-sectional cohort of 80 intact laboratory Beagles spanning 1 to 11 years of age. Canine immune aging is heterogeneous and non-linear. While several absolute leukocyte counts declined with age before rising again in geriatric dogs, serum cytokines exhibited distinct, sex-stratified patterns. Although more cytokines varied significantly with age in males than in females, formal age-by-sex interactions did not remain significant after false discovery rate correction. To explore short-term geroprotective responses, we evaluated 24 young beagles following a 90-day intervention with rapamycin, canagliflozin, or dietary restriction. Rapamycin was associated with the broadest endpoint cytokine response. Canagliflozin showed narrower cytokine differences alongside descriptive body-weight reduction, whereas dietary restriction reduced body weight without altering measured immune endpoints. Given the small group sizes and endpoint-only cytokine measurements, these intervention findings remain exploratory and hypothesis-generating. Together, our findings describe stage-specific hematologic changes and sex-stratified cytokine patterns across the canine lifespan and provide a basis for future longitudinal studies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103705","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":"Mechanistic reprogramming of the mtDNA-cGAS-STING axis in cellular senescence: from mitochondrial homeostatic disruption to inflammatory and immune outcomes.","authors":"Yapei Zhang, Jianing Zhu, Lifan Cui, Sirong Chen, Xin Li, Liwenqin Gao, Xin Chen, Kaizhi Wen, Binbin Zeng, Yayun Qian","doi":"10.1007/s10522-026-10515-z","DOIUrl":"https://doi.org/10.1007/s10522-026-10515-z","url":null,"abstract":"<p><p>In addition to cell cycle arrest, cellular senescence is characterized by disrupted mitochondrial homeostasis, development of the senescence-associated secretory phenotype (SASP), and alterations in the immune microenvironment. Mitochondrial membrane damage, disrupted mitochondrial dynamics, and impaired mitochondrial quality control (MQC) can occur during cellular senescence. These changes may cause mitochondrial DNA (mtDNA) to leak abnormally into the cytosol. Cytosolic mtDNA can then activate cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling. Unlike the acute innate immune response elicited by pathogen-derived DNA, cGAS-STING signaling in senescent cells is mainly activated by the aberrant cytosolic accumulation of endogenous DNA. This signaling activates the TANK-binding kinase 1 (TBK1)-interferon regulatory factor 3 (IRF3) axis and induces a type I interferon response. It also promotes nuclear factor kappaB (NF-κB)-mediated inflammatory transcription, sustains the SASP, and modulates paracrine signaling and immune cell function. This review focuses on mitochondrial structural damage, mtDNA release, and impaired MQC. It summarizes the mechanisms that activate the mtDNA-cGAS-STING axis during cellular senescence and examines its functional changes. It also discusses the potential development of senescence-associated biomarkers. Current evidence suggests that this signaling axis mainly contributes to the maintenance and amplification of the inflammatory senescence phenotype. It is unlikely to independently determine the onset of cellular senescence. Its effects are highly dependent on cell type and pathological context, while assay standards, causal relationships, and therapeutic windows require further clarification.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103702","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":"Presynaptic compensation sustains neuromuscular transmission in the mouse diaphragm at a late stage of aging.","authors":"Andrei N Tsentsevitsky, Arthur N Khaziev, Guzel V Sibgatullina, Vadim V Salnikov, Anna R Tokmakova, Venera F Khuzakhmetova, Jilia G Odnoshivkina, Ellya A Bukharaeva, Alexey M Petrov","doi":"10.1007/s10522-026-10516-y","DOIUrl":"https://doi.org/10.1007/s10522-026-10516-y","url":null,"abstract":"<p><p>The diaphragm is the primary respiratory muscle. Like other skeletal muscles, it is subject to age-related changes, but it may be more resistant to sarcopenia due to compensatory mechanisms operating at the neuromuscular junction (NMJ). Here, we examined key parameters of neuromuscular transmission in the diaphragm of 24- and 3-month-old mice. In aged NMJs, a decrease in the amplitude of evoked postsynaptic responses in combination with a much greater reduction in miniature end-plate amplitude occurred. This was accompanied by an increase in spontaneous exocytosis intensity, presynaptic action potential propagation velocity, the quantal content of end-plate potentials upon single stimuli, and the asynchronous component of the evoked release. Moreover, aged NMJs exhibited increased exocytosis of acetylcholine quanta during short-term stimulus trains at 10-70 Hz and especially prolonged intermittent nerve stimulation at 20 Hz. The facilitation of neurotransmitter release between bursts (a sign of synaptic vesicle mobilization) and the estimated size of the readily releasable pool both increased with age. This correlated with a decrease in vesicle clustering and immunolabeling of synapsin 1, a protein restraining vesicles in the nonactive pool. Monitoring the exocytotic release of FM1-43 dye from synaptic vesicles suggested an increase in vesicle recycling rate during 20-Hz activity in aged NMJ. Thus, enhanced neurotransmitter release, probably due to increases in readily releasable pool size and synaptic vesicle mobilization, may partially compensate for the decrease in the postsynaptic membrane response to a single acetylcholine quantum in aged diaphragm NMJs. Such adaptations are likely necessary to preserve diaphragmatic function with aging.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149103632","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":"Peptone-free nematode growth medium improves culture stability and physiological resilience in Caenorhabditis elegans.","authors":"Priyaranjan Mandal, Sourabh Behra, Aarika Kasliwal, Kamesh R Babu","doi":"10.1007/s10522-026-10513-1","DOIUrl":"https://doi.org/10.1007/s10522-026-10513-1","url":null,"abstract":"<p><p>Nematode growth medium (NGM) has been the standard culture medium for Caenorhabditis elegans (C. elegans) for over five decades and contains peptone to support proliferation of the bacterial food source, Escherichia coli OP50. However, the increasing use of paraformaldehyde (PFA)-killed OP50 in studies of metabolism, aging, and host-microbe interactions raise the question of whether peptone remains necessary once bacterial proliferation has been eliminated. Here, we systematically compared conventional and peptone-free NGM using PFA-killed OP50 as the bacterial food source. Peptone removal completely prevented residual bacterial proliferation and markedly reduced fungal contamination, thereby improving culture stability. Although worms cultured on peptone-free NGM exhibited reduced food preference and pharyngeal pumping, they maintained normal growth, reproduction, embryonic viability, lifespan, and chemotactic behavior. Peptone-free NGM also reduced basal intracellular reactive oxygen species (ROS) and lipid accumulation, accompanied by downregulation of genes involved in oxidative stress responses and lipogenesis. In addition, worms displayed enhanced locomotor activity and significantly greater resistance to oxidative, ultraviolet, and thermal stress. Collectively, these findings demonstrate that peptone is dispensable when PFA-killed OP50 is used as the bacterial food source. Peptone-free NGM therefore represents a simple, inexpensive, and practical refinement of the conventional culture system for C. elegans studies employing PFA-killed bacterial diets.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149069143","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":"Perilla frutescens extract reduces fat accumulation and promotes longevity in Caenorhabditis elegans via modulation of the insulin/IGF-1 signaling pathway.","authors":"Lianghao Huang, Fengyu Yin, Xingdao Fu, Yurong Huang, Yixuan Tang, Guiyan Liao, Bin Wang, Ting Yang, Gang Huang, Xing Chen","doi":"10.1007/s10522-026-10507-z","DOIUrl":"https://doi.org/10.1007/s10522-026-10507-z","url":null,"abstract":"<p><p>Perilla frutescens (PF) is rich in flavonoids and other secondary metabolites with antioxidant properties. This study explored the lifespan-modulating effects and underlying mechanisms of an ethyl acetate extract of PF leaves (EAEPF) using Caenorhabditis elegans (C. elegans) as a model organism. EAEPF treatment significantly prolonged lifespan, enhanced pharyngeal pumping and head thrashing frequencies, and reduced the accumulation of lipofuscin and reactive oxygen species (ROS). The extract improved antioxidant enzyme activity, decreased malondialdehyde (MDA) levels, and increased resistance to thermal and juglone-induced oxidative stress. EAEPF markedly reduced lipid storage in nematodes, indicating a lipid-lowering effect. Mechanistically, EAEPF activated the insulin/IGF-1 signaling (IIS) pathway, and upregulated the transcription factors DAF-16/FOXO and SKN-1/Nrf2, which in turn promoted the expression of downstream stress-response genes (sod-3, gst-4, hsp-16.2). EAEPF reprogrammed lipid metabolism and enhanced glutathione metabolism, may represent a potential source of nutritional hormetins. These findings demonstrated the potential of EAEPF as a nutraceutical for lifespan extension and healthspan improvement.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057957","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":"Turnera diffusa polysaccharides promote healthy aging through conserved stress response regulation and metabolic remodeling across multiple aging models.","authors":"Hailing Wang, Rui Wu, Xuemei Zhang, Xin Meng","doi":"10.1007/s10522-026-10514-0","DOIUrl":"https://doi.org/10.1007/s10522-026-10514-0","url":null,"abstract":"<p><p>Aging is a progressive decline in physiological functions and the capacity to maintain homeostasis, representing a major risk factor for numerous chronic diseases. Geroprotectors, defined as natural or synthetic compounds capable of improving healthspan and delaying age-associated functional decline, have attracted increasing attention in aging research. However, clinically validated interventions for promoting healthy aging remain unavailable. Plant-derived polysaccharides, owing to their excellent safety profiles and diverse biological activities, have emerged as promising candidates for geroprotection. Turnera diffusa Willd. Ex Schult. (T. diffusa) has been reported to exhibit neuroprotective and reproductive system modulating properties; however, the geroprotective potential of its polysaccharides remains unexplored. In the present study, T. diffusa polysaccharides (TDP) were found to significantly extend lifespan and alleviate multiple age-associated physiological declines in both C. elegans and D. melanogaster models. Mechanistic investigations revealed that TDP enhanced the activation of conserved DAF-16/FOXO and HSF-1-mediated stress response pathways, thereby promoting antioxidant defense and maintaining proteostasis. Furthermore, ¹H-NMR-based metabolomic analysis demonstrated that TDP partially restored age-related metabolic disturbances, particularly those associated with amino acid, energy, and lipid metabolism. These findings provide novel insights into the geroprotective potential of TDP and support its further investigation as a potential geroprotective candidate.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057960","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":"Erigeron breviscapus alleviates senescence via AMPK-SIRT1 signaling by modulating FOXO3a-mediated antioxidant defense and p53-dependent apoptosis.","authors":"Yuanzhu Pu, Can Su, Xinyi Wang, Haifeng Chen","doi":"10.1007/s10522-026-10511-3","DOIUrl":"https://doi.org/10.1007/s10522-026-10511-3","url":null,"abstract":"<p><p>Erigeron breviscapus Hand-Mazz. (EBHM) is a well-documented herbal medicine with recognized antioxidant, anti-apoptotic, and anti-inflammatory bioactivities. However, its anti-senescence effects and the underlying mechanisms remain poorly understood. Here, we investigated the anti-senescence potential of EBHM employing Caenorhabditis elegans and SAMP8 mice. In C. elegans, EBHM treatment prolonged the average lifespan of C. elegans to a maximum of 18.68%, while also significantly enhancing stress resistance and motor function. The lifespan-extending effects of EBHM were abolished in mutants of aak-2, sir-2.1, daf-16, and cep-1. EBHM treatment increased p-AMPK/AMPK ratio and elevated levels of SIR-2.1 protein, facilitated the nuclear import of DAF-16::GFP as well as the upregulation of SOD-3::GFP expression, lowered MDA content, and enhanced the enzymatic activities of SOD, GSH-Px and CAT through a DAF-16-dependent mechanism. Furthermore, EBHM downregulated the mRNA levels of the pro-apoptotic genes cep-1and ced-3 (CASP3 homolog), while upregulating the anti-apoptotic gene ced-9 (Bcl-2 homolog) in C. elegans. In SAMP8 mice, EBHM reduced SA‑β‑gal‑positive cells, collagen deposition, and α-SMA expression in the liver and kidney, elevated the p-AMPK/AMPK ratio and SIRT1 expression, decreased levels of acetyl-FOXO3a, p53, acetyl-p53, p16, and p21, lowered MDA levels while enhancing antioxidant enzyme activities, diminished the proportion of apoptotic cells, downregulated Bax and CASP3, and upregulated Bcl-2. Collectively, these findings suggest that EBHM prolongs lifespan and healthspan in C. elegans and ameliorates aging‑associated tissue alterations in SAMP8 mice through activation of the AMPK-SIRT1 pathway, which enhances FOXO3a-dependent antioxidant defenses and modulates p53-mediated apoptosis, thereby alleviating oxidative stress and cellular damage.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057922","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":"Mesenchymal stem/stromal cell senescence in aging and regenerative medicine: a systematic review.","authors":"Letícia Odaguiri Watanabe, Luana Roleto Cardoso, Johnny Carvalho da Silva, Larissa Di Carvalho, Vitoria Castro, Juliana Lott Carvalho, Eliete Guerra, Taia Maria Berto Rezende","doi":"10.1007/s10522-026-10501-5","DOIUrl":"10.1007/s10522-026-10501-5","url":null,"abstract":"","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13615060/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149057909","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":"Cellular senescence and the SASP in skeletal ageing: convergent mechanisms of progressive bone loss in osteoporosis.","authors":"Haotian Liu, Bingjun Lei","doi":"10.1007/s10522-026-10508-y","DOIUrl":"https://doi.org/10.1007/s10522-026-10508-y","url":null,"abstract":"<p><p>Skeletal ageing involves changes in endocrine regulation, mechanical loading and cellular function that can impair bone remodelling. Cellular senescence and the senescence-associated secretory phenotype (SASP) have emerged as mechanisms that help close this gap. In the ageing bone microenvironment, senescent osteocytes, mesenchymal stem cells, osteoblasts, immune cells, and vascular endothelial cells secrete pro-inflammatory cytokines, chemokines, matrix metalloproteinases, and Wnt antagonists such as sclerostin. Rather than acting as a parallel pathway, these factors converge on the same RANKL/OPG, Wnt/β-catenin, and NF-κB axes through which classical triggers operate, adding a locally generated, persistent input that promotes resorption and suppresses formation. Clearance of senescent cells prevents age-related bone loss in mice, indicating that the SASP is a distinct and independently addressable contributor to skeletal ageing. Here we review the components, regulation, and cell type-specific profiles of the bone-related SASP, and its differential involvement across age-related, postmenopausal, and secondary osteoporosis. We also assess senolytic and senomorphic approaches in relation to established osteoporosis treatments, discussing source-specific mechanisms, biomarker validation and longer-term skeletal outcomes as priorities for evaluating these approaches.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023793","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":"Tissue-specific aging clocks map structured aging-modulatory drug-score patterns across 49 human tissue and cell-line categories.","authors":"Dongdong Zhang","doi":"10.1007/s10522-026-10512-2","DOIUrl":"https://doi.org/10.1007/s10522-026-10512-2","url":null,"abstract":"<p><p>Aging clocks are typically trained on pooled multi-tissue data, implicitly assuming that aging is uniform across organs. Here we challenge this assumption by constructing 49 transcriptomic clocks across 47 tissue types and 2 cell-line categories from GTEx v8 (948 unique donors contributing to the retained clock categories) using donor-grouped cross-validation. Clocks achieved a median Pearson r of 0.543 (best: artery aorta, r = 0.855). We identified 10,253 unique clock genes, of which 69.2% appeared in only one tissue; however, null simulation confirmed that this low overlap is the expected consequence of sparse elastic-net selection rather than biological tissue-specificity. We then projected 3,926 LINCS L1000 compound-name entries onto each clock to build a drug × category age-reversal matrix. At a permissive threshold (|score|> 1.0), 94.2% of drugs showed mixed score directions (positive in some categories and negative in others). This permissive mixed-direction proportion was descriptive and did not itself exceed shuffled expectations. Under a more stringent exploratory criterion requiring |score|> 2.0 in at least three categories in each direction, 2.8% of compound entries showed pronounced bidirectional divergence, compared with approximately 0.1% under the shuffled null. Compound rankings remained stable when analysis was restricted to the 34 clocks with r ≥ 0.5 (Spearman ρ = 0.897 versus the full analysis). A Jaccard-based enrichment statistic yielded highly concordant compound rankings (median per-category Spearman ρ = 0.961), indicating that results were not artifacts of the enrichment method. After Benjamini-Hochberg FDR correction across all 192,374 drug-category pairs, only 0.79% reached FDR < 0.05, indicating that individual drug-category calls require caution. Rapamycin showed net pro-aging transcriptional signatures in our system; we explicitly emphasize that transcriptome-based scores and organismal lifespan are distinct endpoints. DepMap CRISPR analysis was repeated after GTEx-based standardization across 13 matched categories, although individual gene-level results were limited. Four statistical robustness tests confirmed model stability. These findings describe category-associated drug-score patterns and provide a tissue-aware resource for generating hypotheses about drug responses, while cautioning against over-interpretation of individual drug-category predictions without experimental validation.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 5","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-09-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149023805","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}