Aging and Disease最新文献

{"title":"Senolytic Treatment Triggered by Carotid Occlusion Confers Protection Against Later Acute Ischemic Stroke in Aged Rats.","authors":"Szilvia Kecskés, Péter Makra, Tamás Monostori, Zoltán Veréb, Ferenc Bari, Ákos Menyhárt, Eszter Farkas","doi":"10.14336/AD.2026.0537","DOIUrl":"https://doi.org/10.14336/AD.2026.0537","url":null,"abstract":"<p><p>Advanced age is associated with larger infarct volumes and poorer functional recovery after acute ischemic stroke (AIS). Carotid stenosis is also a common comorbidity in older individuals and often predicts subsequent AIS. However, no age-specific therapy is currently available to protect the aging brain from aggravated ischemic injury. Here, we investigated whether a senolytic approach could improve cerebrovascular status and reduce ischemic brain injury in a comorbid aging model of AIS. Unilateral common carotid artery occlusion was induced in young and aged rats and served as a diagnostic trigger for chronic senolytic therapy with dasatinib plus quercetin (D+Q). Two weeks later, the distal middle cerebral artery was occluded for 60 min. Compared with vehicle-treated animals, infarct size was measured, spreading depolarizations (SDs) were recorded electrophysiologically, cerebral blood flow (CBF) dynamics were monitored by laser speckle contrast imaging, and cerebrovascular senescent cell burden was assessed by immunocytochemistry. Cerebral angiogenesis, central and systemic inflammatory markers, and metabolic status were evaluated using protein arrays and blood glucose measurements. Aged rats developed larger infarcts than young controls, and this age-related increase was attenuated by D+Q treatment. D+Q reduced the higher frequency of SDs observed in the aged ischemic brain. Increased cerebrovascular senescence in aged animals was diminished by D+Q, accompanied by enhanced angiogenesis, although CBF responses to SDs and reperfusion were unchanged. In addition, D+Q modulated central and systemic inflammatory profiles and counteracted age-related metabolic impairment. Senolytic D+Q therapy administered after carotid artery occlusion confers multifaceted protection against subsequent AIS in the aged brain. By targeting fundamental aging mechanisms that exacerbate brain vulnerability to AIS, D+Q enhanced the resilience of the aging neurovascular niche. Long-term neurological outcomes were not assessed in the present study; therefore, the results provide a rationale for further investigation of senolytic strategies in age-related stroke vulnerability.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Profiling Reveals Divergent Kidney and Brain Immune Responses during Metabolic Syndrome.","authors":"Laura Van der Taelen, Sara M P Lambrichts, Lieve Temmerman, Romaysa El Ajjouri, Marion J Gijbels, Nicole Bitsch, Jean Scheijen, Marjo van de Waarenburg, Martina Kutmon, Thomas Unger, Julie Staals, Casper G Schalkwijk, Ana M Briones, Robert J van Oostenbrugge, Sébastien Foulquier","doi":"10.14336/AD.2026.0557","DOIUrl":"https://doi.org/10.14336/AD.2026.0557","url":null,"abstract":"<p><p>Chronic kidney disease (CKD) and cerebral small vessel disease (cSVD) share major cardiometabolic risk factors, including hypertension, diabetes, and obesity. The immune system may play a key role in kidney-brain interactions and disease development. However, whether circulating inflammatory mediators reflect similar immune responses in the kidney and brain remains unclear. We therefore characterized circulating, renal and cortical cerebral responses in a rat model of metabolic syndrome. Lean and Obese ZSF1 rats were studied at 8-9, 22-23, and 34-35 weeks of age. Systemic inflammation was assessed using multiplex plasma cytokine/chemokine analysis and flow cytometry of circulating immune cells. Kidney injury was evaluated by histopathology and expression of injury markers. Renal and cerebral blood flow were measured by Laser Speckle Contrast Imaging. Renal macrophage accumulation and cortical cerebral immune cell readouts were assessed by immunohistochemistry. Progression of metabolic syndrome in Obese ZSF1 rats was associated with elevated circulating inflammatory mediators, including IP-10, MCP-1, and RANTES, together with increased classical monocytes from 8-9 weeks and non-classical monocytes from 22-23 weeks onward. Kidney pathology was further characterized by progressive macrophage accumulation and reduced renal blood flow. In contrast, cortical cerebral analyses showed no evidence of macrophage infiltration, while CD68 positivity was reduced in Iba1+ microglia in Obese rats at 34-35 weeks. Despite marked systemic inflammation and renal immune activation, the cerebral cortex displayed a distinct immune response with no macrophage infiltration and altered microglial activity. Rather than indicating a uniform inflammatory response across organs, these descriptive findings provide insight into kidney-brain immune divergence during metabolic syndrome.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148886028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-Nucleus RNA-Seq of Human and Rat Cardiomyocytes Identifies Shared and Distinct Regulators and Features of Aging and Disease.","authors":"Samaneh Ekhteraei-Tousi, Rosa Doñate Puertas, Mohamad Youness, Onne A H O Ronda, Magnus Aronsen, Emil K S Espe, Arne Olav Melleby, Ida Marie Hauge-Iversen, Ella Cutsforth, Lirong Li, Emma L Robinson, Einar Sjaastad Nordén, Mani Sadredini, Filip Rega, Kenneth C Bedi, Kenneth B Margulies, Karin R Sipido, Ivar Sjaastad, H Llewelyn Roderick","doi":"10.14336/AD.2026.0357","DOIUrl":"https://doi.org/10.14336/AD.2026.0357","url":null,"abstract":"<p><p>Age is the greatest risk factor for cardiovascular diseases, including heart failure (HF), which is a leading cause of morbidity and mortality. While left ventricular fibrosis, hypertrophy and decreased contractility are associated with cardiac aging, age is not sufficient for HF development. Despite diminished cardiomyocyte (CM) function being central to cardiac pathology, whether factors predisposing the aged CM to disease are the same or distinct from those underlying disease are not determined. To address this, we integrated our own and published single-nucleus RNA-Seq data of different cardiomyopathies and from young and old human samples and probed for unique and overlapping features. To test the utility of rodents for modelling human aging and disease, we compared human data with data from deeply phenotyped relevant rat models. We identified diverse CM substates, which were significantly altered in proportion with pathology in human and in both pathology and age in rat. In human and rat, CM exhibited substantial transcriptomic changes with age and pathology. In addition to established hallmarks of cardiomyopathy and aging, we detected etiology/age-specific differentially expressed genes/pathways and identified candidate nodal regulators underlying these changes. In human and rat, CM exhibited greater cellular and transcriptional heterogeneity in pathology and age. While rats showed substantial differences to humans, overlapping features, including increased CM heterogeneity and altered expression of genes related to epigenetic, fibrotic and hypertrophic remodelling, were also detected. Although some pathways, differentially expressed genes and trajectories are shared between age and pathology, unique aspects support age and pathology as distinct entities.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710977","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex as a Missing Moderator in the Dual-Pathway Neuroprotection Hypothesis.","authors":"Zehui Gong, Liang Xiang, Jianrong Yuan, Zhaobing Xiang","doi":"10.14336/AD.2026.0914","DOIUrl":"https://doi.org/10.14336/AD.2026.0914","url":null,"abstract":"<p><p>The Dual-Pathway Neuroprotection Hypothesis, recently proposed by Badea and colleagues, distinguishes voluntary from enforced exercise and links each to distinct neural pathways, moving beyond the unitary view of exercise as a homogeneous intervention. However, the hypothesis does not consider sex as a biological variable. Given that AD is a sex-biased disease affecting approximately 65-70% women, and that the neuroprotective effects of exercise are sexually dimorphic, we argue that sex may function as a critical moderator of this framework. We propose three testable predictions: (1) voluntary exercise's cortico-limbic effects may be potentiated in females through estrogen-BDNF signaling, but this effect may be constrained by menopausal status; (2) structured/supervised exercise may yield sex-divergent outcomes-with preliminary observations suggesting Aβ clearance in females versus neurotrophic upregulation in males-though evidence remains preliminary and derives from a limited number of heterogeneous studies; and (3) stress burden may reduce the net benefit of enforced exercise, but this will require direct testing. These predictions converge on a formal revision in which sex is not a confounder to be controlled for, but a core biological moderator that may moderate modality-specific neuroprotection. This extended model provides a hypothesis-generating framework for designing future sex-aware exercise studies in AD, but does not yet support sex-stratified clinical prescriptions. This framework is predominantly based on preclinical and indirect evidence from heterogeneous models, necessitating cautious interpretation and rigorous validation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710993","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"KDM4C inhibition reinforces NK cell cytotoxicity through the cGAS-STING pathway in TP53-mutated AML.","authors":"Xinyi Zhang, Huilan Liu, Liangquan Geng, Panpan Huang, Mengqing Gao, Qian Fan, Kaishuang Jiang, Na Zhao, Xuxu Zhao, Huaiping Zhu, Cihangir Duy, Haiming Wei, Dongyao Wang","doi":"10.14336/AD.2026.0432","DOIUrl":"https://doi.org/10.14336/AD.2026.0432","url":null,"abstract":"<p><p>TP53-mutated acute myeloid leukemia (AML) is associated with an extremely poor prognosis and is refractory to conventional chemotherapy and allogeneic hematopoietic stem cell transplantation (allo-HSCT). We identified high expression of lysine demethylase 4C (KDM4C) in AML, particularly in TP53-mutated AML. Pharmacological inhibition of KDM4C with QC6352 predominantly induced apoptosis in TP53-wild-type AML cells, whereas it caused limited apoptosis but pronounced senescence and growth arrest in TP53-mutated AML cells. In TP53-mutated AML cells, QC6352 induced senescence-associated cytosolic DNA accumulation and activated the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway, leading to the upregulation of NK cell-activating ligands and enhancing NK cell-mediated cytotoxicity. In vivo, QC6352 effectively attenuated AML progression, and its combination with NK cell therapy further reduced leukemic burden and prolonged survival in mice. Collectively, these findings demonstrate that pharmacological KDM4C inhibition with QC6352 induces cellular senescence and enhances the intrinsic immunogenicity of TP53-mutated AML cells through activation of the cGAS-STING pathway. The study supports KDM4C inhibition as a potential therapeutic strategy for TP53-mutated AML, particularly in patients receiving NK cell-based immunotherapy or undergoing allo-HSCT.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Old Hosts, Young Models: Rethinking Cancer Immune Evasion in Aging.","authors":"Nigar Karimova, Leyla Karimova, Bayram Bayramov, Rena Karimova","doi":"10.14336/AD.2026.0738","DOIUrl":"https://doi.org/10.14336/AD.2026.0738","url":null,"abstract":"<p><p>Cancer is largely a disease of older adults, yet the framework used to explain how tumors evade immunity was built almost entirely on young, specific-pathogen-free mouse models and on clinical trials that under-enroll older adults. This review examines whether that framework holds when the host is old. Rather than surveying cancer immunology and aging comprehensively, it focuses on one question: whether the four host capacities the standard account of immunoediting and checkpoint blockade assumes still hold in the aged host. These are a naive T-cell repertoire wide enough to generate tumor-specific clones, a stromal environment that does not suppress priming, functional natural killer [NK] cell surveillance, and an immune baseline free of chronic inflammation. Aging alters all four, but not uniformly. Thymic involution and NK cell decline result in the immune system operating at reduced capacity, representing a shift in severity rather than a fundamental change in mechanism. The NK cell axis is disproportionately significant, as no approved therapies currently restore its function. In contrast, aged stromal senescence and inflammaging represent qualitative changes: the tissue environment becomes suppressive prior to tumor development, rather than as a consequence of tumor presence. The clinical evidence neither confirms nor refutes this interpretation. Older and younger patients gain similar benefit from checkpoint blockade, which is easily read as age being immunologically irrelevant. We argue instead that chronological age bundles aging changes acting on response in opposite directions. What predicts response is more accurately captured by immunological age than by chronological age. This reframing has a clear translational consequence. Therapeutic approaches should not only target the release of suppressed immune responses but also address the correction of the aged microenvironment. This hypothesis is currently being evaluated by senolytic strategies, which have been tested in an initial clinical trial and are supported by converging preclinical evidence.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal Clustering Identifies Different Rates of Cortical Aging in Healthy Older Adults.","authors":"Benita Schmitz-Koep, Fabian Bongratz, Vivian Schultz, Aurore Menegaux, Melissa Thalhammer, Severin Schramm, Su Hwan Kim, Claus Zimmer, Jan S Kirschke, Christian Sorg, Christian Wachinger, Panteleimon Giannakopoulos, Marie-Louise Montandon, Cristelle Rodriguez, Sven Haller, Dennis M Hedderich","doi":"10.14336/AD.2026.0434","DOIUrl":"https://doi.org/10.14336/AD.2026.0434","url":null,"abstract":"<p><p>Global trajectories of brain aging are well-characterized thanks to many large MRI datasets in the general population. However, regional patterns that may reflect individual differences in brain aging remain less well understood. In this study, we aim to identify differences in brain aging in a longitudinal study of healthy older individuals using a clustering approach and test predictors of cluster membership. Cortical thickness (CTh) is an important biomarker of cortical macrostructure, relevant both in normal aging processes and in many pathologies. CTh was assessed in 176 healthy individuals aged 68-85 years at two time points (mean time interval: 5 ± 1 years) using T1-weighted magnetic resonance imaging (MRI). Regional cortical atrophy was identified based on the annualized percent change (APC) of CTh. Different aging clusters were then classified using hierarchical cluster analysis based on APC values. Two clusters emerged: one with minimal atrophy and the other with more pronounced atrophy of CTh, particularly in left prefrontal and central regions. There were no significant group differences in age or sex between the two clusters. The cluster with more pronounced atrophy was significantly associated with education in the univariate analysis and at borderline significance in the adjusted analysis and showed a non-significant trend of association with cognitive decline. Our results indicate different rates of cortical aging within the context of healthy aging processes.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148710987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Interpreting Divergent Short-Chain Fatty Acid Effects in Alzheimer's Disease: A Seven-Axis Framework.","authors":"Shuo Liu, Danrui Han, Tao Bai, He Chen, Jian-Ping Li","doi":"10.14336/AD.2026.0777","DOIUrl":"https://doi.org/10.14336/AD.2026.0777","url":null,"abstract":"<p><p>Studies of short-chain fatty acids (SCFAs) in Alzheimer's disease (AD) report protective, neutral, and adverse findings, but the same class label often conceals non-equivalent exposures and endpoints. We propose an AD-specific interpretive framework that organizes this heterogeneity as a causal sequence: source or intervention → SCFA species, dose, and route → absorption and metabolic filtering → target-compartment exposure → host and disease state → responding cell type → endpoint. Seven interdependent axes-SCFA species, dose, route, compartment, exposure context, disease stage, and responding cell type-identify the coordinates needed to compare studies. This organization separates administered dose from achieved exposure, direct entry into the central nervous system from blood-brain barrier or peripheral gut-brain signaling, and stage-related disease biology from evidence of stage-specific treatment efficacy. It also requires symmetric interpretation of null findings according to exposure verification, target engagement, power, cellular resolution, and endpoint specificity. The framework integrates rather than replaces established microbiome, pharmacological, and neuroimmune principles and has not been validated as a predictor of effect direction. Its explanatory value can be tested by prespecified meta-regression, variance partitioning, interaction analysis, matched-exposure replication, and causal mediation. Persistent opposite effects under matched coordinates would indicate missing dimensions or failure of the framework. This Perspective therefore supports mechanism-linked, biomarker-informed research rather than nonspecific SCFA supplementation in unselected patients.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711041","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Endocrino-Immuno-Senescence and Its Correlation with Age-Related Diseases: Molecular Insights into Immunomodulatory Strategies for Healthy Aging.","authors":"Pulak R Manna, Shengping Yang, Chayan Manna, Hafiz Khan, P Hemachandra Reddy","doi":"10.14336/AD.2026.0585","DOIUrl":"https://doi.org/10.14336/AD.2026.0585","url":null,"abstract":"<p><p>Regulation of the endocrine and immune system is pivotal for bodily homeostasis and healthy physiology, and these processes deteriorate as life progresses from adulthood to senescence. Aging, progressively weakening the structural and functional efficacies of the hypothalamic-pituitary-thyroid-adrenal-gonadal autoregulating axis, results in endocrino-immuno-senescence (EIS) that modulates a variety of complications and diseases. Both endocrine and immune responses are compromised during aging, along with impaired tissue regeneration, weakened pathogen detection, and decreased immune surveillance, and these events increase the susceptibility to infection, autoimmunity, cancers, and chronic disorders. Nonetheless, while immunosenescence modulates systemic inflammation and overall host defense, inflammaging accelerates tissue deterioration and intensifies diverse pathologies. Dysregulation of hormonal, genetic, and epigenetic machineries dampens the immune system, elevates pro-inflammatory activity, and fails to defend an organism against foreign pathogens, representing a link between cellular dysfunction and EIS. To mitigate these events, immunomodulation is an important therapeutic strategy that helps renew endocrine and immune dysregulation and simultaneously diminish age health disparities. Moreover, preservation of hormonal stability, involving immune response, emerges as a central determinant and could serve as a preventive medicine for the health and well-being of aged populations. This review provides a comprehensive understanding of the mechanisms by which EIS is coordinately associated with a variety of pathological processes and delineates new insights into immunomodulatory strategies ameliorating age-related diseases for healthy aging and quality living.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial Inflammation and Muscle Aging: Targeting the Inflammatory Microenvironment in Sarcopenic Muscle.","authors":"Xuesong Wang, Shannah Erasmus, Zewen Chu, Xiaomin Tu, Tursen Alima, Yajie Tao, Lei Fang","doi":"10.14336/AD.2026.0331","DOIUrl":"https://doi.org/10.14336/AD.2026.0331","url":null,"abstract":"<p><p>Sarcopenia is an age-related progressive degenerative disorder of skeletal muscle characterized by declining muscle mass, strength, and function. Increasing evidence indicates that chronic low-grade inflammation plays an important contributory role in its pathogenesis. The inflammatory microenvironment contributes to sarcopenia through complex interactions involving cellular senescence, mitochondrial dysfunction, and sustained inflammatory signaling, forming a self-reinforcing pathological cycle within skeletal muscle. This review synthesizes current evidence on the molecular mechanisms underlying inflammation-driven sarcopenia, with particular emphasis on how inflammatory signaling disrupts protein turnover and satellite cell metabolism. In addition, exercise is examined as a precision \"hormone-like\" intervention tailored to different sarcopenia phenotypes, highlighting the distinct mechanisms through which resistance training, aerobic exercise, and combined training modulate the senescence-associated phenotype and inflammatory responses. The review further evaluates anti-inflammatory therapeutic strategies, including nutritional interventions, pharmacotherapy, and acupuncture. These approaches improve muscle health by restoring immune balance, enhancing mitochondrial function, modulating the gut-muscle axis, reducing oxidative stress, and promoting the clearance of senescent cells. Finally, emerging precision medicine frameworks and multi-omics strategies that may support individualized sarcopenia management are discussed. Overall, this review provides an integrated perspective on inflammatory signaling in sarcopenia and outlines potential therapeutic strategies targeting the inflammatory microenvironment, offering insights for future research and clinical management.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711000","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}