Biogerontology最新文献

{"title":"Emodin alleviates radiation-induced pulmonary fibrosis by targeting cellular senescence via the mtDNA-cGAS-STING axis.","authors":"Wei Duan, Yanling Sha, Xi Tang, Riu Liu, Bin Su, Meijing Huang, Xin Xun, Yunfei Ye","doi":"10.1007/s10522-026-10472-7","DOIUrl":"10.1007/s10522-026-10472-7","url":null,"abstract":"<p><p>Radiation-induced pulmonary fibrosis (RIPF) is a severe complication of thoracic radiotherapy with limited effective treatment options. Cellular senescence has emerged as a critical driver of age-related tissue fibrosis; however, its role in RIPF and potential as a therapeutic target are underexplored. In this study, we investigated whether emodin, a natural compound with known anti-aging properties, alleviates RIPF by suppressing radiation-induced cellular senescence. In a mouse model exposed to 16 Gy thoracic irradiation, emodin treatment significantly attenuated pulmonary fibrosis, reduced collagen deposition, and downregulated fibrotic markers. Notably, emodin markedly suppressed radiation-induced senescence in pulmonary epithelial cells, accompanied by reduced secretion of senescence-associated secretory phenotype (SASP) factors. Mechanistically, emodin preserved mitochondrial integrity, curbed mitochondrial reactive oxygen species (mtROS) accumulation, and prevented mitochondrial DNA (mtDNA) leakage into the cytoplasm, thereby inhibiting the cGAS-STING-NF-κB signaling pathway, a key pro-inflammatory axis in senescent cells. Importantly, knockdown of cGAS or treatment with the mitochondrial uncoupler CCCP attenuated the anti-senescent effects of emodin, underscoring the centrality of mitochondrial dysfunction and the mtDNA-cGAS-STING axis in senescence-driven fibrosis. Collectively, these findings identify emodin as a novel senescence-targeting agent that mitigates RIPF by alleviating mitochondrial dysfunction and disrupting the mtDNA-cGAS-STING pathway, highlighting its therapeutic potential in age-related fibrotic diseases.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148390043","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":"Natural modulators of enhancer of zeste homolog 2 (EZH2): potential epigenetic regulators of aging-associated pathways.","authors":"Vassiliy Shmarin, Zulfiia Guvatova, Alexey Moskalev","doi":"10.1007/s10522-026-10467-4","DOIUrl":"10.1007/s10522-026-10467-4","url":null,"abstract":"<p><p>The review summarizes the context-dependent role of enhancer of zeste homolog 2 (EZH2) in cellular senescence and aging-associated tissue dysfunction. It discusses a conceptual shift from strong pharmacological EZH2 inhibition toward a more nuanced, context-dependent epigenetic modulation by natural compounds. Aging is associated with tissue‑specific alterations in EZH2 expression-both its decline and overexpression have been linked to cellular senescence, impaired regeneration, and age‑related pathologies, challenging the view of EZH2 as a purely oncogenic target. We critically assess the mechanisms by which natural compounds may influence aging and their potential relevance as candidate EZH2 modulators in geroprotection. The evidence suggests that careful EZH2 modulation may help restore epigenetic balance without disrupting essential chromatin functions. A deeper understanding of EZH2's tissue-specific regulatory networks and downstream effectors is needed to develop safe, epigenetically balanced interventions targeting aging. This knowledge will be essential for advancing the development of novel, safe, epigenetically-targeted geroprotective therapies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148381386","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":"MSC-derived extracellular vesicles accelerate wound healing in senescent fibroblast cultures.","authors":"Ekaterina Rudnitsky, Naomy Vineshtock, Natali Yakubov, Alex Braiman, Yael Segev, Marina Wolfson, Khachik K Muradian, Vera Gorbunova, Gadi Turgeman, Michaela Ben Shahar, Vadim E Fraifeld","doi":"10.1007/s10522-026-10468-3","DOIUrl":"10.1007/s10522-026-10468-3","url":null,"abstract":"<p><p>Wound healing (WH) is a multi-component and highly orchestrated process, in which fibroblasts play a pivotal role. Wound healing is commonly attenuated during aging and the course of cellular senescence (CS). A growing body of evidence demonstrates that mesenchymal stem cell (MSC)-derived extracellular vesicles (EVs) can mitigate the aging and CS phenotype. In this study, we evaluated the effects of EVs derived from naïve MSCs (nMSCs) or anti-inflammatory polarized MSCs (pMSCs) on the rate of in vitro wound healing in primary cultures of human pulmonary fibroblasts (HPF) at various stages of cellular senescence. The major finding of this study is that MSC-derived EVs increase the rate of in vitro WH in senescent but not young HPF cultures. Yet, the pMSC-derived EVs had a stronger impact on WH acceleration in senescent cultures as compared to the nMSC-derived EVs, and this impact was apparently attributed to cell migration.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13328317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148366756","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":"A multi-ingredient food supplement slows age-dependent decline of mobility and influences gene expression in C. elegans.","authors":"Chad Yanyatan, Karthik Mohanraj, Michael Fasseas, Sushmita Maitra, Ed Van Harmelen, Chris Saunter, David Weinkove","doi":"10.1007/s10522-026-10463-8","DOIUrl":"10.1007/s10522-026-10463-8","url":null,"abstract":"<p><p>The goal of developing interventions to slow ageing is not only lifespan extension but more importantly to increase healthspan, the period of life spent in active good health. Nutritional interventions have emerged as a potential strategy to maintain health with age. Testing these interventions for effects on human ageing would take several years and require large cohort sizes. We therefore employed C. elegans as a rapidly ageing model organism to investigate the effects of two commercially available nutrition-based products on ageing-related decline of mobility as an indication of healthspan. These products are multi-ingredient formulations comprising vitamins, minerals, antioxidants, amino acids and botanical extracts. They include compounds expected to positively influence ageing such as Dihydronicotinamide mononucleotide, NAD + booster, trans-resveratrol, taurine, pterostilbene and bioflavonoids. V14™ contains 40 + ingredients and AG1® contains 70 + ingredients with 5 additional probiotic strains. Mobility-based readouts over time were obtained using WormGazer™ imaging technology. Worms exposed to V14™ showed increased movement and speed with age compared to those exposed to AG1® and to a solvent control. To investigate the underlying mechanisms, transcriptomic profiling was performed on V14™ exposed worms, revealing modulation of pathways involved in metabolism and stress responses, processes associated with ageing. Collectively, these findings suggest that V14™ delays age-related decline in C. elegans and highlight the potential of targeted nutritional interventions to modulate pathways relevant to human ageing.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13310222/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337665","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":"Correction: Hormetic efficacy of rutin to promote longevity in Drosophila melanogaster.","authors":"Debarati Chattopadhyay, Atith Chitnis, Aishwarya Talekar, Prajakta Mulay, Manyata Makkar, Joel James, Kavitha Thirumurugan","doi":"10.1007/s10522-026-10462-9","DOIUrl":"10.1007/s10522-026-10462-9","url":null,"abstract":"","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148337644","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":"Identifying potential drug targets for physical and cognitive frailty: an integrative analysis of CHARLS cohort, mendelian randomization, and gene colocalization.","authors":"Wen Liu, Jie Zhao, Zeng-Qiang Liu, Xiao-di Sun, Yuan-Yuan Dong, Yu-Jie Meng, Wei-Dong Jiang, Zhen Liu","doi":"10.1007/s10522-026-10466-5","DOIUrl":"10.1007/s10522-026-10466-5","url":null,"abstract":"<p><p>With the aging of the population, frailty has become a common syndrome that severely affects the quality of life of older adults. This study aims to analyze the correlation between cognition and frailty, physical activity and frailty, and elucidate the potential pharmacological targets of cognitive frailty and physical frailty.We conducted logistic regression analyses using data from the China Health and Retirement Longitudinal Study (CHARLS) to examine the associations between total cognition and frailty, physical activity and frailty. Furthermore, summary-data-based Mendelian randomization (SMR) and two-sample Mendelian randomization (TSMR) were employed to explore potential pharmacological targets for frailty. Genes associated with physical frailty and cognitive frailty were identified, followed by analysis via colocalization analysis, phenome-wide association studies (PheWAS), and DsigDB drug prediction. Cross-sectional analysis of CHARLs revealed that total cognition(OR 0.93, 95% CI 0.92-0.95) and middle physical activity(OR 0.95, 95% CI 0.92-0.97) were negatively correlated with frailty. SMR identified 41 drug genes associated with frailty, and subsequent TSMR validation and co-localization analysis showed that 11 candidate genes exhibited strong colocalization (PP.H4 > 0.8). GRPEL 1, PABPC 4, and WBP 2NL were ultimately identified as potential drug targets associated with physical frailty, while LANCL1, LRPPRC, FADS1, and WBP2NL were identified as potential drug targets associated with cognitive frailty. Phenome-wide association analysis(PheWAS) did not reveal any significant associations between these genes and other phenotypes at the genome-wide significance threshold. Laudanosine, 25-hydroxycholesterol, and hexadecanal emerged as the top three candidate compounds for therapeutic intervention. We identified potential drug targets for physical frailty and cognitive frailty through comprehensive analysis and elucidated drugs associated with potentially relevant genetic markers, thereby laying the foundation for a deeper understanding of the mechanisms of frailty.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148306695","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":"RNA-binding proteins in aging and age-related diseases: roles, mechanisms, and a large language model analysis.","authors":"Qunhua Han, Shunmei Huang, Suisui Luo, Dianqiang Yang","doi":"10.1007/s10522-026-10464-7","DOIUrl":"10.1007/s10522-026-10464-7","url":null,"abstract":"<p><p>Aging is a progressive and irreversible biological process that contributes to the pathogenesis of numerous age-related diseases. Elucidating the molecular mechanisms of aging is crucial for promoting healthy aging and extending healthspan. RNA-binding proteins (RBPs) are pivotal regulators of post-transcriptional gene expression and play essential roles in diverse biological processes. RBPs interact with both coding and non-coding RNAs to regulate RNA metabolism, stability, localization, and translation. Dysregulated RBP-RNA interactions have been closely associated with aging and age-related diseases. This review systematically summarizes the structural characteristics of RBPs and the evolution of methods used to study them. We focus on the molecular mechanisms of six key RBPs, namely HuR, AUF1, TTP, IGF2BP2, QKI, and LARP7, in the context of aging and age-related diseases. In addition, we discuss the regulatory functions of post-translational modifications of RBPs. Furthermore, we provide a multidimensional overview of RBP involvement in aging and age-related diseases through large language model (LLM)-based text-mining analysis. Our study provides a foundation for the comprehensive characterization of RBPs in aging and age-related diseases.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148293300","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":"Hyperspectral imaging and healthy aging: an observational study using hand skin as surface for monitoring healthy aging processes.","authors":"Maddalena M Bolognesi, Teresa Sassetti, Martina Caramenti, Chiara Ceriani, Gloria Bertoli, Tecla Aramini, Marcella Bonanomi, Daniela Gaglio, Michele Caccia, Francesca Gallivanone","doi":"10.1007/s10522-026-10461-w","DOIUrl":"10.1007/s10522-026-10461-w","url":null,"abstract":"<p><p>With the global rise in life expectancy, promoting healthy aging has become a central focus in biomedical research. From global initiatives like The World Health Organization's Decade of Healthy Ageing (2021-2030) to local ones, they highlight the need for accessible, non-invasive, and cost-effective tools to monitor aging-related physiological changes. Since the hand skin is an easily accessible tissue, it can offer valuable insights into aging processes, influenced by age, gender, and environment, as suggested by the paradigm of One Health. In this study, we exploited the potential of Visible and Near-Infrared Hyperspectral Reflectance Imaging (Vis-NIRHSI) as a quantitative, non-invasive method for monitoring skin aging in healthy individuals. A dataset of 101 hand-skin hypercubes images, from healthy volunteers over 40 years old, was acquired with a dedicated camera and analyzed in the range of 410 - 820 nm. A total of 224 spectral and texture features were extracted at selected wavelengths to investigate age-related variations in skin properties and to establish a standard reference map. Among these, 15 were retained as significant descriptors of the aging process and were used to build reference curves for the \"healthy status condition.\" A questionnaire about quality and perception of lifestyle was administered to describe the sampled population in terms of exposome. Our findings suggest that hyperspectral skin analysis can serve as a promising biomonitoring approach for assessing aging dynamics and may contribute to the development of reliable tools for supporting healthy aging monitoring strategies.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13275750/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148263146","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":"Unlocking the aging brain: mTORC1 as a convergent integrator for neurodegeneration and therapeutic intervention.","authors":"Mokhtar Rejili, Hayder M Al-Kuraishy, Mustafa M Shokr, Gaber El-Saber Batiha","doi":"10.1007/s10522-026-10457-6","DOIUrl":"10.1007/s10522-026-10457-6","url":null,"abstract":"<p><p>Aging is the primary risk factor for neurodegenerative diseases, characterized by a progressive decline in cellular homeostasis. Central to this process is the mammalian target of rapamycin complex 1 (mTORC1), a convergent integrator regulator of metabolism that integrates nutrient sensing with cellular growth. While essential for development, chronic mTORC1 hyperactivity, termed mTORopathy, emerges during aging, driving a deleterious cycle of mitochondrial dysfunction, neuroinflammation, and impaired protein clearance. This pathological state promotes the accumulation of toxic proteins, such as amyloid-beta, tau, and alpha-synuclein, while simultaneously suppressing autophagy and glymphatic function. Furthermore, mTORC1 overactivation in glial cells fuels inflammaging by inducing cellular senescence and the senescence-associated secretory phenotype (SASP), which compromises blood-brain barrier integrity and synaptic plasticity. Conversely, pharmacological inhibition of mTORC1 using rapamycin or its analogs (rapalogs) has demonstrated significant neuroprotective potential. By restoring autophagic flux, rebalancing metabolic axes (AMPK/SIRT1), and suppressing chronic inflammation, these compounds can rescue synaptic function and reactivate neurogenesis. This review synthesizes current evidence regarding mTORC1 as a convergent integrator for brain aging and evaluates the clinical prospects of mTOR-targeted therapies in mitigating neurodegenerative decline.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249091","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":"Nacre extract attenuates age-related functional and tissue alterations under post-onset intervention conditions in two murine aging models.","authors":"Momoko Kawaminami, Saki Kimoto, Hana Yamamoto, Yasushi Hasegawa","doi":"10.1007/s10522-026-10459-4","DOIUrl":"10.1007/s10522-026-10459-4","url":null,"abstract":"<p><p>Aging is accompanied by the accumulation of senescent cells and chronic low-grade inflammation, which together contribute to functional decline and tissue remodeling across organs. We previously reported that long-term nacre extract supplementation can delay age-related deterioration when initiated early; however, whether it can provide benefit under post-onset intervention conditions remains unclear. Here, we evaluated a water-soluble nacre extract derived from Pinctada fucata using (i) senescence-accelerated mouse prone 8 (SAMP8) mice and (ii) a D-galactose-induced aging paradigm, with treatment administered after the emergence of age-related phenotypes. In SAMP8 mice, nacre extract improved cognitive and neuromuscular performance, including Y-maze spontaneous alternation, novel object recognition, and forelimb grip strength, and showed a partial improvement in composite aging indices. These benefits were accompanied by reduced senescence-associated markers (p16, p21, and phosphorylated histone H2AX (γH2AX)) in skeletal muscle and peripheral organs, suppression of inflammation-associated signaling in skeletal muscle, and improved redox-related marker profiles. Nacre extract also increased satellite cell- and contractile marker-related immunoreactivity in aged skeletal muscle, suggesting improved regeneration- and maturation-related tissue characteristics. In the D-galactose model, nacre extract was introduced after impairments emerged and administered during the final 11 weeks of continued D-galactose exposure; under these post-onset intervention conditions, nacre extract improved grip strength, showed trends toward improved cognitive performance, and reduced senescence-associated markers in skeletal muscle and adipose tissue, supporting reproducibility across paradigms. Collectively, these findings indicate that nacre extract attenuates aging-associated functional and tissue alterations under post-onset intervention conditions by attenuating senescence- and inflammation-associated tissue responses and improving organism-level homeostasis.</p>","PeriodicalId":8909,"journal":{"name":"Biogerontology","volume":"27 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148249089","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}