Aging Cell最新文献

{"title":"The Thymic Microenvironment Shapes Age-Related Qualitative Changes in the TCR Repertoire","authors":"Jasmine Rowell,&nbsp;Diana C. Yanez,&nbsp;Susan Ross,&nbsp;Ching-In Lau,&nbsp;Eden Zhang,&nbsp;Amir Monfared,&nbsp;Oscar A. Peña,&nbsp;Benny Chain,&nbsp;Tessa Crompton","doi":"10.1111/acel.70675","DOIUrl":"https://doi.org/10.1111/acel.70675","url":null,"abstract":"<p>Ageing impairs immune function, increasing susceptibility to infection, autoimmunity and inflammation. The thymus undergoes involution during childhood, and thymocyte and thymic epithelial cell (TEC) numbers decline. Given that adaptive immunity depends on T-cells recognising diverse antigens via their unique T-cell receptor (TCR), the precise age-related changes in TCR repertoire composition are key to understand immunity. To investigate the influence of age on the thymic TCR repertoire we sequenced TCRα and TCRβ transcripts from developmentally defined thymocyte populations from 4-week, 12-month and 18-month-old mice, and from thymocytes recovering from hydrocortisone-treatment, and athymic recipients of RAG1-deficient thymus transplants. The 18-month thymus selected TCR repertoires with distinctive patterns of VxJ and CDR3 k-mer usage compared to young thymus, indicating it had a qualitatively different repertoire with different specificity. It also selected a less diverse TCRβ repertoire with more expanded clones than young thymus. On recovery from hydrocortisone-treatment, both 4-week and 12-month thymus showed bias towards foetal-like 3′TRAVx5′TRAJ rearrangements, but 12-month thymus also produced less diverse and evenly distributed TCRβ repertoires, with increased expansion of TCRβ clones at the CD4⁻CD8⁻CD25⁺CD44⁻intracellularTCRβ⁺ stage, increased TRBJ-1-cluster usage and distinctive patterns of combinatorial VxJ usage. Transplantation of athymic nude recipients with old RAG1-deficient thymus generated less diverse, less evenly distributed TCR repertoires with different combinatorial VxJ usage than those generated by young transplants. Taken together our experiments show that the old thymus generates qualitatively different TCR repertoires than young thymus and the non-lymphoid compartment of the thymus contributes strongly to these changes and to age-associated decline in TCR repertoire diversity.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70675","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Molecular Mechanisms of Age-Related Taste Dysfunction Deciphered by Spatiotemporal Transcriptomics","authors":"Wandong Zhao,&nbsp;Xudong Cha,&nbsp;Yingqi Xie,&nbsp;Enhao Wang,&nbsp;Wenlu Xing,&nbsp;Zengyi Xu,&nbsp;Langchao Liang,&nbsp;Changhai Xiong,&nbsp;Morong Zhou,&nbsp;Penghui Fu,&nbsp;Zhe Wang,&nbsp;Xin Liu,&nbsp;Yiqun Yu,&nbsp;Huanhai Liu,&nbsp;Hanbo Li,&nbsp;Wenwen Ren","doi":"10.1111/acel.70674","DOIUrl":"https://doi.org/10.1111/acel.70674","url":null,"abstract":"<p>Age-related taste dysfunction impairs nutrition and quality of life, contributing to metabolic disorders and frailty in the elderly, yet its cellular and molecular basis remains poorly understood. By integrating single-cell RNA and spatial transcriptomics sequencing, we systematically mapped murine taste bud aging across five developmental stages from neonatal to aged. Our findings reveal that age-associated taste impairment is driven by the progressive depletion of stem/progenitor cell differentiation capacity, predominantly characterized in the posterior tongue, and mediated by inflamm-aging responses and micro-environmental alterations. Specifically, we identified macrophage infiltration and polarization shifts in aged circumvallate and foliate papillae, underscoring the crucial role of macrophages in age-related taste decline. A co-culture model using taste organoids with conditioned media from polarized macrophage revealed that M1-polarized cells suppress taste organoid proliferation and differentiation. Mechanistically, this inhibition may be mediated by macrophage-derived Thbs1, as recombinant Thbs1 treatment directly suppressed taste progenitor cell expansion in vitro. Together, this study provides the first comprehensive spatiotemporal atlas of taste bud aging and identifies novel therapeutic targets for the treatment of age-related taste disorders.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70674","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Surviving Fibroblasts After Treatment With Mitomycin C Exhibit SASP-Like Phenotype After Glaucoma Filtration Surgery","authors":"Akitoshi Kimura,&nbsp;Tomokazu Fujimoto,&nbsp;Satoshi Iraha,&nbsp;Kei-Ichiro Yasunaga,&nbsp;Miyuki Inoue-Mochita,&nbsp;Naofumi Funagura,&nbsp;Shunsuke Tanigawa,&nbsp;Daisuke Kurotaki,&nbsp;Tomoaki Koga,&nbsp;Fumika Watanabe-Kitamura,&nbsp;Utako Tsutsumi-Kuroda,&nbsp;Mitsuyoshi Nakao,&nbsp;Toshihiro Inoue","doi":"10.1111/acel.70680","DOIUrl":"https://doi.org/10.1111/acel.70680","url":null,"abstract":"<p>The clinical outcomes of trabeculectomy, a standard glaucoma filtration surgery (GFS), have dramatically improved with the introduction of mitomycin C (MMC), an antimetabolite widely used to inhibit postoperative scarring. MMC exerts anti-scarring effects primarily by promoting apoptosis and suppressing fibroblast proliferation at the surgical site. However, despite these beneficial effects, MMC also induces the production of inflammatory cytokines, and its full mechanism of action remains incompletely understood. Moreover, a subset of patients continues to experience poor surgical outcomes even after MMC application, highlighting the need for complementary therapeutic strategies. Comprehensive transcriptomic analysis of postoperative GFS tissues revealed that MMC promoted the expression of genes associated with cellular senescence and inflammatory responses. Supporting this, in vitro experiments suggested that the transcriptional changes were associated with MMC-induced senescence-associated secretory phenotype (SASP)-like changes in the fibroblasts. Single-cell RNA sequencing (scRNA-Seq) analyses of postoperative GFS tissues also revealed that fibroblasts after GFS with MMC secrete SASP factors. Furthermore, Cell–Cell communication analysis identified CCL7 as one of the key molecules involved in inflammatory cell migration and the promotion of fibrosis. Importantly, we demonstrated that fibroblasts exhibiting SASP-like features can be selectively eliminated by a specific senolytic agent, suggesting a novel and promising therapeutic approach that may improve long-term surgical outcomes after GFS.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70680","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784820","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aged Mitochondrial DNA Is Associated With Aberrant Acute Exercise-Induced Redox Responses in Human Skeletal Muscle","authors":"Bradley A. Ruple,&nbsp;Nicholas A. Carlini,&nbsp;Jason S. Kofoed,&nbsp;Helya Rostamkhani,&nbsp;Brady E. Hanson,&nbsp;Jesse C. Craig,&nbsp;Shelby C. Osburn,&nbsp;Allison M. Manuel,&nbsp;Paul A. Stewart,&nbsp;Jonathan Wanagat,&nbsp;Ryan M. Broxterman,&nbsp;Joel D. Trinity","doi":"10.1111/acel.70678","DOIUrl":"https://doi.org/10.1111/acel.70678","url":null,"abstract":"<p>Redox imbalances and mitochondrial dysfunction are key contributors to age-related declines in skeletal muscle and may contribute to impaired exercise responsiveness. Here, we investigated the influence of aging on skeletal muscle redox at rest and in response to acute exercise, examining how mitochondrial quality and quantity relate to skeletal muscle redox status. Skeletal muscle biopsies were obtained from 12 young (22 ± 4 years) and 10 older adults (66 ± 7 years) before and immediately after 60-min of high-intensity knee-extension exercise. We assessed mitochondrial respiration, mitochondrial DNA (mtDNA) copy number and deletion mutation frequency at baseline, while skeletal muscle redox proteomics was performed on pre- and post-exercise biopsies in a subset of participants. Mitochondrial respiration was preserved with age (max respiration, <i>p</i> = 0.123). However, the older adults had a lower mtDNA copy number (<i>p</i> = 0.046) and higher mtDNA deletion frequency (<i>p</i> = 0.001), with widespread remodeling of the skeletal muscle redox proteome, including altered thiol occupancy of proteins involved in metabolism, immune function, and extracellular matrix organization. In response to exercise, young skeletal muscle exhibited predominantly reversible peptide reductions, whereas preferential oxidation of mitochondrial antioxidant proteins, including PRDX3, occurred in older muscle. Both mtDNA deletion frequency and mitochondrial respiration were strongly associated with exercise-induced redox modifications in mitochondrial proteins. These findings suggest that aging alters both the regulation and resolution of exercise-induced redox signaling, with mitochondrial genomic instability and respiration shaping redox responsiveness.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 9","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70678","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148784821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Featured Cover","authors":"Dandan Zhong,&nbsp;Chang Hao,&nbsp;Mengyue Li,&nbsp;Jing Liu,&nbsp;Zheng Xu,&nbsp;Jianteng Zhou,&nbsp;Lu Zhao,&nbsp;Siyu Ni,&nbsp;Zhenchao Hu,&nbsp;Yue Sun,&nbsp;Yingying Zou,&nbsp;Dong Sun,&nbsp;Hao Guo,&nbsp;Zhanjun Jia,&nbsp;Dong Guo,&nbsp;Jun-Li Cao,&nbsp;Ying Sun","doi":"10.1111/acel.70665","DOIUrl":"https://doi.org/10.1111/acel.70665","url":null,"abstract":"<p>Cover legend: The cover image is based on the article <i>Podocyte mPGES-2 Determines Renal Aging and Contributes to Senile Osteoporosis</i> by Dandan Zhong et al., https://doi.org/10.1111/acel.70609.\u0000 <figure>\u0000 <div><picture>\u0000 <source></source></picture><p></p>\u0000 </div>\u0000 </figure></p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/acel.70665","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148753556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondria Dictate Progressive Versus Bimodal Aging of the Mammary Gland","authors":"Edmund Charles Jenkins,&nbsp;Mrittika Chattopadhyay,&nbsp;Thelma Mashaka,&nbsp;Miguel Torres-Martin,&nbsp;Daniela Sia,&nbsp;Igor Bado,&nbsp;Doris Germain","doi":"10.1111/acel.70661","DOIUrl":"10.1111/acel.70661","url":null,"abstract":"<p>The incidence of breast cancer shows its largest peak around the age of 65 but also a peak around 45 indicating a bimodal distribution. While some potential explanations, such as age-related enrichment in specific breast cancer sub-types and BRCA1/2 mutations were proposed, they do not explain why the peaks are at 45 and 65, raising the possibility that the way the breast ages may play a role. Here using two mouse models, we show two distinct aging patterns of the mammary gland; one being progressive, the other bimodal. In the bimodal model, waves of overlapping genes and proteins associated with breast cancer pathways are observed at 11 and 19 months but are absent at 3 and 14 months. Further, in the bimodal model, the mammary glands at 11 and 19 months are more permissive to the growth of cancer cells but not at 14 or &gt; 22 months, while in the progressive model, the growth of cancer cells increases starting at 14 months of age. Using scRNAseq, we established a bimodal aging signature. Since 11 and 19 months in mice correlate with 45 and 65 in humans, we tested the mammary gland-derived bimodal signature in two breast cancer databases and found that the signature is enriched in women diagnosed at 45 and 65. Therefore, our study raises the possibility that distinct patterns of aging of the breast exist and that they may contribute to the bimodal distribution of breast cancer. Further, our study adds to the growing evidence of non-linear aging.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13454215/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148700174","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of Physical Activity on Brain White Matter Integrity Are Region-, Dose-, and Age-Dependent: Findings From the Population-Based Rhineland Study","authors":"Eva Saxler,&nbsp;Fabienne A. U. Fox,&nbsp;Alexandra Koch,&nbsp;Xingwang Yang,&nbsp;Weiyi Zeng,&nbsp;Santiago Estrada,&nbsp;Monique M. B. Breteler,&nbsp;N. Ahmad Aziz","doi":"10.1111/acel.70659","DOIUrl":"10.1111/acel.70659","url":null,"abstract":"<p>White matter integrity is a sensitive marker of cerebrovascular health and aging. Physical activity may promote white matter health, but previous studies were limited by self-reported activity and small sample sizes. We examined the association between accelerometer-based physical activity and novel indices of white matter integrity while identifying potential mediators. We analyzed cross-sectional baseline data from 4188 participants (58% women, mean age: 55.4 years) of the Rhineland Study, a prospective cohort study in Bonn, Germany. Physical activity measures (independent variables) were derived from activPAL3 micro-accelerometers. Fractional anisotropy, mean diffusivity, free water fraction, orientation dispersion, and neurite density (outcomes) were obtained from 3 T MR images for the whole brain and across 27 white matter tracts. We performed multivariable polynomial regression and mediation analyses for cardiometabolic and inflammatory factors. Higher energy expenditure was related to lower orientation dispersion, with the association leveling off at higher amounts (standardized <i>β</i>_linear = −0.153 [−0.183; −0.122]; <i>β</i>_quadratic = 0.034 [0.017; 0.051]; both <i>p</i> &lt; 0.001). Physical activity was linked to lower neurite density in motor tracts (<i>β</i>s between −0.133 and −0.056, all <i>p</i> &lt; 0.001). However, with advancing age, physical activity became more strongly associated with higher neurite density and lower mean diffusivity of supratentorial fibers. Body weight, cardiometabolic, and inflammatory factors partly mediated effects of physical activity on white matter microstructure. Physical activity is related to white matter integrity in a nonlinear, age- and region-specific way. Physical activity's effects are greatest in sedentary and older individuals, likely mediated through its impact on body composition, cardiometabolic health, and systemic inflammation.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13451344/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148688362","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"HNRNPC Succinylation Influences the Neurodegeneration of Alzheimer's Disease Through YME1L1-Mediated Mitochondrial Metabolism","authors":"Xuewei Li,&nbsp;Fan Yang,&nbsp;Yuyan Jiang,&nbsp;Fei Zhao,&nbsp;Fan Liu","doi":"10.1111/acel.70646","DOIUrl":"10.1111/acel.70646","url":null,"abstract":"<p>Mitochondrial dysfunction and abnormal energy metabolism are important pathological features of Alzheimer's disease (AD). This study investigates how mitochondrial protease YME1L1 affects mitochondrial function and its upstream regulation in the pathogenesis of AD. The AD model was established by using APP/PS1 transgenic mice, primary neurons treated with Aβ1-42, and HT22 cells. The silencing of YME1L1 was achieved to evaluate its effects on mitochondrial function and OPA1 protein hydrolysis. RIP-qPCR and RNA pull-down test were used to evaluate the interaction between HNRNPC and YME1L1 mRNA. The protein succinylation level was detected by proteomic analysis of succinylation, and co-immunoprecipitation (Co-IP) was used to verify the succinylation of HNRNPC. Cognitive ability was tested by behavioral tests, including the Morris water maze, Y-maze, object recognition test, and olfactory test. Finally, the therapeutic potential of SIRT5 was studied by an overexpression experiment in an AD model. YME1L1 was significantly upregulated in the AD model, which promoted mitochondrial dysfunction and neuronal damage through OPA1 hydrolysis. HNRNPC enhances the stability of YME1L1 mRNA through an m6A-dependent mechanism, while its own K50 succinylation enhances the stability of HNRNPC by competitively inhibiting TRIM25-mediated ubiquitination, further amplifying the expression of YME1L1. SIRT5 downregulation in AD elevated HNRNPC succinylation levels. SIRT5 overexpression promoted HNRNPC desuccinylation, reduced YME1L1 expression, restored mitochondrial function, and ameliorated Aβ deposition and cognitive deficits in AD mice. The SIRT5-HNRNPC-YME1L1 axis contributes to AD pathogenesis by disrupting OPA1 proteolysis and mitochondrial dynamics. Targeting HNRNPC succinylation represents a promising therapeutic strategy for AD.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13443708/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148676304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endothelial AGGF1 Deficiency Causes Mitochondrial Dysfunction and Contributes to Age-Elevated Blood Pressure","authors":"Weixin Lv,&nbsp;Xiaojuan Zhong,&nbsp;Qiang Yuan,&nbsp;Xueting Gong,&nbsp;Ya Zhao,&nbsp;Shilin Zhang,&nbsp;Andong Wu,&nbsp;Ming Wan,&nbsp;Xueer Li,&nbsp;Yangyi Zheng,&nbsp;Jiankun Liu,&nbsp;Bingbing Zhou,&nbsp;Yuanzheng Zhu,&nbsp;Limin Zhao,&nbsp;Qiquan Wang,&nbsp;Yang Xiang,&nbsp;Xiao-Li Tian","doi":"10.1111/acel.70652","DOIUrl":"10.1111/acel.70652","url":null,"abstract":"<p>Endothelial cells are critical in the regulation of blood pressure. We previously demonstrated AGGF1 was crucial for maintaining endothelial cell function. This study aims to examine whether AGGF1 regulates blood pressure. Here, we found that AGGF1 expression was inversely correlated with blood pressure with age. In male mice, endothelial-specific loss of function of <i>Aggf1</i> (<i>Aggf1</i>^{<i>flox/flox</i>}<i>/Tie2-Cre</i>⁺) significantly increased blood pressure, whereas endothelial-specific human <i>AGGF1</i> overexpression (TGM(Tie2-hAGGF1)) suppressed age-elevated blood pressure. The endothelial-specific loss of AGGF1 accelerated early vascular aging, characterized by increased arterial stiffness, impaired endothelium-dependent vasorelaxation, reduced eNOS phosphorylation, and augmented ROS production, whereas AGGF1 overexpression rescued these phenotypic changes. Mechanistically, we found that nuclear-localized AGGF1 bound to the SESN2 promoter and enhanced its transcription. This upregulation of SESN2 attenuated mitochondrial dysfunction, including respiratory dysfunction and elevated mitochondrial ROS, and ultimately led to increased p-eNOS levels and improved endothelial function. Furthermore, SESN2 overexpression rescued early vascular aging and reduced blood pressure in <i>Aggf1</i>^{<i>flox/flox</i>}<i>/Tie2-Cre</i>⁺ mice, while SESN2 knockdown attenuated the beneficial vascular effects of AGGF1. Together, we demonstrate that endothelial AGGF1/SESN2/p-eNOS is a novel and important signaling axis in the maintenance of blood pressure. Age suppresses the AGGF1/SESN2/p-eNOS signaling cascade, leading to an elevation of blood pressure. Our study provides new insights into age-elevated blood pressure in male mice and suggests AGGF1 as a potentially valuable target for prehypertension intervention in the elderly male population.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13430426/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148662936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the Lactate Receptor GPR81 Ameliorates Senescence Hallmarks and Improves Muscle Function in Cellular and Progeroid Models of Aging","authors":"Pihu Mehrotra,&nbsp;Sai Harsha Bhamidipati,&nbsp;Pedro Lei,&nbsp;John Toftegaard,&nbsp;Debanik Choudhury,&nbsp;Maryam Elsayed,&nbsp;Yali Zhang,&nbsp;Jianmin Wang,&nbsp;Shweta Chitkara,&nbsp;G. Ekin Atilla-Gokcumen,&nbsp;Song Liu,&nbsp;Stelios T. Andreadis","doi":"10.1111/acel.70647","DOIUrl":"10.1111/acel.70647","url":null,"abstract":"<p>Skeletal muscle aging is associated with increased lipid accumulation, or myosteatosis, leading to lipotoxicity and loss of muscle function. Here, we report that loss of the lactate receptor GPR81 in cellular and progeroid models of muscle aging is associated with impaired lipid oxidation and enhanced lipid accumulation. Knockdown of GPR81 in young healthy myoblasts led to an increase in senescence hallmarks such as DNA damage, accumulation of reactive oxygen species (ROS), impaired mitochondrial activity, and autophagy. Conversely, treatment of senescent myoblasts with GPR81 agonists enhanced lipid oxidation, leading to a decrease in lipid accumulation, ultimately resulting in decreased DNA damage, ROS accumulation, and enhanced ability to form myotubes. In agreement with our in vitro findings, we observed significant improvement in muscle regeneration and overall health of progeric mice that were treated with GPR81 agonists. Our findings suggest that GPR81 plays a key role in skeletal muscle lipid metabolism, and agonists of GPR81 might play a promising role in reversing age-associated lipid accumulation and loss of muscle function.</p>","PeriodicalId":55543,"journal":{"name":"Aging Cell","volume":"25 8","pages":""},"PeriodicalIF":7.7,"publicationDate":"2026-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13429102/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148652581","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}