Aging and Disease最新文献

{"title":"Cellular Senescence Drives Diabetic Atherosclerosis: Aging Mechanisms and Integrative Therapeutic Implications.","authors":"Yu Deng, Guangtao Pan, Shanyan Chen, Xiang Jia, Xu Zhang, Tianle Wang, Aochuan Sun, Zhengtang Liu, Mishan Wu, Chaojun Chen","doi":"10.14336/AD.2026.0182","DOIUrl":"https://doi.org/10.14336/AD.2026.0182","url":null,"abstract":"<p><p>Cellular senescence is increasingly recognized as a key mechanism linking aging to chronic disease. Diabetic atherosclerosis (DAS), a major macrovascular complication of type 2 diabetes, often progresses despite standard metabolic and lipid-lowering therapies, highlighting the involvement of aging-related processes beyond classical metabolic and inflammatory pathways. This review synthesizes evidence to propose a conceptual framework in which stress-induced senescence is a key disease-oriented aging mechanism contributing to DAS initiation and progression. Hyperglycemia and lipotoxicity induce premature senescence in endothelial cells, vascular smooth muscle cells, and macrophages through oxidative stress, mitochondrial dysfunction, and activation of the NLR Family Pyrin Domain Containing 3 (NLRP3) inflammasome. Senescent cells secrete a senescence-associated secretory phenotype (SASP), which amplifies chronic vascular inflammation, promotes plaque instability, and facilitates systemic propagation of senescence, thereby contributing to multi-organ dysfunction in the heart, brain, and kidneys. Together, these features position DAS as a representative model of stress-accelerated vascular aging. From a therapeutic perspective, we discuss emerging senescence-targeted strategies, including senolytics, senomorphics, and multi-target interventions derived from integrative medicine, with emphasis on their potential to modulate the aging tissue microenvironment and delay disease progression. By framing diabetic atherosclerosis within the context of aging biology, this review provides a disease-focused perspective on mechanisms and therapeutic opportunities underlying age-associated vascular disorders.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809216","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":"Circadian Rhythm, Clock Genes and Osteoarthritis: The Dream of a Good Night's Sleep.","authors":"Hong Xu, Xinzhan Mao, Qichen Long, Antonia Rujia Sun, Indira Prasadam, Ross Crawford, Yang Chen, Yanping Wang, Xiwei Fan","doi":"10.14336/AD.2026.0105","DOIUrl":"https://doi.org/10.14336/AD.2026.0105","url":null,"abstract":"<p><p>Circadian rhythm is an endogenous 24-hour timing system that coordinates metabolic, inflammatory, and reparative processes required for tissue homeostasis. Disruption of this temporal organization, increasingly common because of shift work, sleep disturbance, and other modern lifestyle factors, has been implicated in chronic inflammatory and metabolic diseases, including osteoarthritis (OA). Experimental studies indicate that circadian dysregulation in joint tissues can alter chondrocyte metabolism, extracellular matrix turnover, synovial inflammatory tone, and subchondral bone remodeling. At the molecular level, perturbation of core clock components such as BMAL1, PER, and CRY is associated with oxidative stress, an imbalance between anabolism and catabolism, and increased sensitivity to inflammatory stimuli. Human evidence currently supports an association between circadian misalignment, disturbed sleep, and greater OA symptom burden, but direct causal inference remains limited. OA-related pain, reduced physical activity, and metabolic dysfunction may, in turn, aggravate sleep and circadian disruption, creating a bidirectional cycle. This review synthesizes mechanistic, animal, and human evidence on circadian regulation of joint homeostasis and discusses translational opportunities, including chronotherapy, rhythm-aligned behavioral interventions, and pharmacological modulation of clock pathways. We also highlight major limitations of the current literature and priorities for future phase-informed precision studies in OA.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809278","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":"Peanut Procyanidin A Delays Hematopoietic Stem Cells Aging through Cox5a.","authors":"Ying Wang, Bingzheng Zhang, Junfei Lu, Lin Liu, Xiaoyu Tang, Changzheng Li, Xi Zeng, Chuqing Fan, Yuncong Qiao, Cheng Chen, Yu Zhang, Jiajia Chen, Zhiyi Li, Yucheng Luo, Guizhi Yang, Juan Shen, Bing Liu","doi":"10.14336/AD.2025.1354","DOIUrl":"https://doi.org/10.14336/AD.2025.1354","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) are essential for maintaining blood system homeostasis. Their aging leads to functional decline and increased susceptibility to blood disorders, largely driven by elevated reactive oxygen species (ROS). Here, we identify peanut procyanidin A (PPA) as a potent compound that delays HSC aging by targeting cytochrome c oxidase subunit 5a (Cox5a). Through screening of 234 FDA-approved natural compounds, we found that PPA significantly reduces mitochondrial ROS and improves the function of aged HSCs in mice. Transcriptomic analysis revealed that PPA induces a metabolic shift from oxidative phosphorylation toward glycolysis, reminiscent of a youthful HSC state. Moreover, PPA rescues aging phenotypes in human CD34+ hematopoietic progenitor cells. Our study establishes Cox5a as a druggable target for HSC rejuvenation and highlights PPA as a promising therapeutic candidate for age-related hematopoietic decline.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809249","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":"Therapeutic Potential of Micheliolide and ACT001 in Age-Related Diseases: Molecular Mechanisms and Clinical Prospects.","authors":"Hui Xu, Xin Cong, Lian-Jun Lin","doi":"10.14336/AD.2025.1556","DOIUrl":"https://doi.org/10.14336/AD.2025.1556","url":null,"abstract":"<p><p>Aging is the predominant risk factor for several chronic disorders; therefore, elucidating the molecular and cellular mechanisms underlying age-related pathologies is essential for therapeutic advancement. Micheliolide (MCL), a naturally occurring guaianolide sesquiterpene lactone derived from Michelia champaca and Michelia compressa, has attracted increasing attention for its pharmacological potential. Its derivative, ACT001, enables the sustained release of MCL into the plasma in vivo, thereby enhancing oral bioavailability and improving therapeutic efficacy. ACT001 has recently received orphan drug designation for glioblastoma treatment, highlighting its clinical feasibility and safety profile. Increasing evidence indicates that MCL regulates age-related diseases by modulating inflammation, cell cycle, mitochondrial dysfunction, oxidative stress, and autophagy. By targeting key signaling pathways, including NF-κB, STAT3, NRF2, AMPK, and NLRP3, MCL/ACT001 demonstrated its protective effect against age-related diseases. This paper summarizes the current mechanistic insight and disease-specific evidence regarding MCL/ACT001 and further evaluates their therapeutic repositioning potential for age-related diseases, including cardiovascular and cerebrovascular diseases, fibrotic conditions, immune disorders, metabolic diseases, and tumors. Additionally, we discussed key translational challenges.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809320","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":"Aging-Associated CCL8⁺ Senescent Macrophages Recruit CCR1⁺ Neutrophils to Promote NETs Formation and Impair Meningeal Lymphatic Drainage.","authors":"Ye Yuan, Ruoli Wang, Qiuguang He, Zhongyi Zhang, Xuan Wu, Jing Yi, Junyi Chen, Yuxin Xie, You You, Linhui Zhang, Ziyi Yang, Shengwan He, Yihao Tao, Zongyi Xie","doi":"10.14336/AD.2026.0132","DOIUrl":"https://doi.org/10.14336/AD.2026.0132","url":null,"abstract":"<p><p>Meningeal lymphatic vessels (mLVs) are essential for central nervous system (CNS) waste clearance and brain homeostasis, yet their functional decline during aging remains poorly understood. Here, through integrated single-cell and bulk transcriptomic analyses, we identify a distinct macrophage subset characterized by high CCL8 expression (CCL8⁺ macrophages) that accumulates in aged meninges and exhibits a pronounced senescence-associated secretory phenotype (SASP). Trajectory analysis positions CCL8⁺ macrophages at a senescence-associated terminal differentiation state. Mechanistically, CCL8⁺ macrophages engage in pro-inflammatory crosstalk with neutrophils via the CCL8-CCR1 axis, promoting aberrant neutrophil recruitment and excessive neutrophil extracellular traps (NETs) formation within meningeal lymphatic niches. These NETs structurally and functionally impair meningeal lymphatic drainage. Importantly, pharmacological inhibition of CCR1 with BX471 or enzymatic degradation of NETs with DNase I restores meningeal lymphatic function and ameliorates spatial learning and memory deficits in aged mice. Notably, CCR1 antagonist BX471 has previously been evaluated in early human clinical trials and shown favorable tolerability, supporting the translational feasibility of targeting this pathway. In addition, machine learning approaches identify a robust predictive gene signature associated with this senescent macrophage phenotype. Collectively, our findings reveal a previously unrecognized macrophage-neutrophil-NETs axis that links meningeal immunosenescence to meningeal lymphatic dysfunction and cognitive decline and may represent a promising therapeutic target for aging-related neurodegenerative disorders.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809095","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":"Inflammaging: From Mechanisms to Clinical Implications and Targeted Interventions.","authors":"Rola S Zeidan, Aditya S Shirali, Simon Reinhard, Anna Picca, Patricia Vial, Lisiane Pruinelli, Joe G N Garcia, Christian Leeuwenburgh, Stephen Anton","doi":"10.14336/AD.2025.1557","DOIUrl":"https://doi.org/10.14336/AD.2025.1557","url":null,"abstract":"<p><p>Inflammaging refers to the chronic, low-grade, sterile inflammatory state that emerges as a hallmark of biological aging and is increasingly recognized as a contributor to functional decline, frailty, and the progression of multiple age-associated diseases. While acute inflammation supports host defense and tissue repair, persistent and unresolved inflammatory signaling promotes tissue damage, metabolic dysregulation, and impaired immune homeostasis. Inflammaging reflects a dysregulated physiological state associated with elevated damage-associated molecular patterns (DAMPs), pro-inflammatory cytokines, altered immune cell composition, metabolic imbalance, and the accumulation of senescent cells exhibiting a senescence-associated secretory phenotype (SASP). Together, these processes impair immune surveillance, increase oxidative stress, and tissue vulnerability, potentially accelerating functional decline and amplifying disease trajectories that may originate earlier in life. Despite ongoing challenges in precisely defining and measuring inflammaging, evidence suggests that its development is shaped not only by chronological aging but also by behavioral, environmental, psychosocial, and genetic factors, highlighting its dynamic and potentially modifiable nature. In this review, we distinguish inflammaging from general chronic inflammation, synthesize current understanding of its biological origins and mechanistic drivers, and examine its role in clinical outcomes including sarcopenia, neurodegeneration, and cardiovascular disease. We propose a conceptual translational framework linking biological mechanisms of inflammaging to multilayer biomarker signatures, AI-based risk stratification, and precision interventions. Additionally, we discuss the opportunities and limitations of these approaches for identifying individuals at risk for chronic disease and informing multi-dimensional strategies to promote resilience and extend health-span.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809287","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":"Perceived Hypoacusis and Loneliness: A Longitudinal Between- and Within-Individual Association in Mexican Older Adults.","authors":"Liliana Giraldo-Rodríguez, Diana Ramos-Félix, Paloma Roa-Rojas, Karen Eloina Pérez-D'Aquino, Teresa Álvarez-Cisneros","doi":"10.14336/AD.2025.1199","DOIUrl":"https://doi.org/10.14336/AD.2025.1199","url":null,"abstract":"<p><p>Hearing loss is highly prevalent among older adults and is associated with negative psychosocial outcomes such as loneliness. Loneliness is a major public health concern due to its links with functional decline, morbidity, and mortality. While international studies have identified associations between hearing loss and loneliness, few examine this relationship longitudinally, particularly in Latin America. Furthermore, little is known about whether these associations arise from structural differences between individuals or from changes within the same individual over time. We conducted a longitudinal observational study using data from the 2015, 2018, and 2021 waves of the Mexican Health and Aging Study (MHAS). The sample included participants aged 60 years and above with complete data on hearing, loneliness, and covariates. Subjective hearing was self-reported and loneliness was measured using the short-form UCLA scale. A hybrid random-effects model was employed to separate between-individual differences from within-individual changes, adjusting for sociodemographic characteristics, health conditions, and functional status. Progressive subjective hearing decline within the same individual was significantly associated with greater loneliness (p < 0.01), independent of socioeconomic and health factors. Between-individual effects lost significance after adjustment, suggesting that cross-sectional differences may be explained by underlying health and social conditions. Functional disability and multiple chronic conditions independently predicted loneliness. Progressive subjective hearing loss was associated with higher loneliness scores, highlighting the importance of valuing patients' self-reported hearing experiences. Findings underscore the need for timely hearing interventions, integrated geriatric assessments, and policies that address sensory health as part of healthy aging strategies.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809349","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":"Targeting PPAR Signaling for Neurovascular Protection: Advances in Natural Product-Based Therapeutics.","authors":"Xinyi Ouyang, Yijing Xiang, Longbiao Tan, Jiali Zou, Yufan Long, Kangwen Ning, Shuang Zhang, Fenglin Wang, Ting Liu, Dan Huang, Huiping Liu, Guomin Zhang","doi":"10.14336/AD.2026.0094","DOIUrl":"https://doi.org/10.14336/AD.2026.0094","url":null,"abstract":"<p><p>Central nervous system diseases such as ischemic stroke, cerebral hemorrhage and Alzheimer's disease have high fatality and disability rate. Their common pathological mechanisms involve neuroinflammation, oxidative stress, mitochondrial dysfunction and blood-brain barrier damage. As a ligand-dependent nuclear transcription factor, peroxisome proliferator activated receptor (PPARs) plays a key role in lipid metabolism, energy homeostasis and inflammation regulation. In particular, PPAR-γ shows significant neurovascular protective effect through multiple signaling axes such as NF-κB, Nrf2 and AMP-activated protein kinase (AMPK). In recent years, a large number of studies have confirmed that a variety of natural products (e.g., flavonoids, phenolic acids, glycosides and triterpenes) can activate or regulate the PPAR pathway, mediate anti-inflammatory, antioxidant, prevent blood-brain barrier damage and promote neurotrophic factor expression, thereby improving the pathological phenotype of ischemic or degenerative encephalopathy. In addition, some components (such as Stevioside, Catalpol, Morin, etc.) have shown potential PPAR regulatory ability, but lack direct validation in encephalopathy models, and are worth further exploration. In conclusion, natural products targeting PPAR signal have the comprehensive advantages of multiple pathways and multiple targets, which represent an important direction for the intervention of cerebrovascular diseases. In the future, we should strengthen the verification of \"component pathway phenotype\" association, combine multi-omics and structural optimization strategies, so as to promote the development of natural product PPAR modulators to precision and transformation applications.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809374","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":"The Relationship between Ergothioneine, Allantoin and Neocortical Amyloid Load.","authors":"Shaun Eslick, Irwin Cheah Kee-Mun, Pratishtha Chatterjee, Sarah Jerome, Barry Halliwell, Ralph Martins","doi":"10.14336/AD.2026.0091","DOIUrl":"https://doi.org/10.14336/AD.2026.0091","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is characterised by hallmark pathology of amyloid beta (Aβ) plaques and hyperphosphorylated tau neurofibrillary tangles in the brain. Ergothioneine (ET) is a potent antioxidant, and anti-inflammatory compound that has shown potential as a therapeutic for neurodegenerative disease*. Cross-sectional analyses of cognitively normal individuals aged 65-90yrs from the Kerr Anglican Retirement Village Initiative in Ageing Health (KARVIAH) cohort were stratified by amyloid status (Aβ+, SUVR >1.35). Plasma ET, its metabolites and urinary allantoin, were quantified by liquid chromatography-mass spectrometry. Plasma Aβ1-40, Aβ1-42, GFAP, and NFL were measured by SIMOA and pTau181 and pTau231 were measured via ELISA. No differences in plasma ET or metabolites were observed between AB- (n=65) and AB+ (n=35) groups. Partial correlation analysis highlighted positive correlations between allantoin, and NFL (r = 0.40, pFDR < 0.01), pTau181 (r = 0.47, pFDR < 0.01) and GFAP (r = 0.31, pFDR = 0.01). Partial correlation by subgroup, revealed positive correlations between plasma ET (r = 0.48, pFDR = 0.05) with Aβ42/40 in the AB+ group only. Evidence indicates that ET may protect the brain from oxidative damage and neuroinflammation. Higher urinary allantoin levels were associated with higher plasma AD biomarkers. Further, plasma ET levels were higher in individuals with a higher AB42/40 ratio, within the AB+ group, suggestive that high ET may potentially have neuroprotective effects. More research will be imperative to validate the significance of ET as a therapeutic for prevention of cognitive decline.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809352","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":"Chronic Swimming Routine Promotes Gut Microbiota Remodeling and Improvements in Physical Resilience, Episodic-Like Memory, and Inflammatory Status in Late Middle-Aged Mice.","authors":"Paola Llanos, Ronakarina Pires-Valero, Johana Rojas-Paillal, Jamileth More, Francisco Silva-Olivares, Luan Americo da Silva, Camila Astudillo-Guerrero, Pamela J Urrutia, Fernanda Figueroa-Ajraz, Claudia Ibacache-Quiroga, Yulia A Nevzorova, Francisco J Cubero, Gonzalo Jorquera","doi":"10.14336/AD.2026.0192","DOIUrl":"https://doi.org/10.14336/AD.2026.0192","url":null,"abstract":"<p><p>Population aging is associated with progressive declines in physical and cognitive function driven by chronic low-grade inflammation and dysregulation of interconnected biological systems. Within the geroscience framework, we tested whether chronic swimming initiated in late midlife attenuates age-related deficits by modulating body composition, systemic and hippocampal inflammation, episodic-like memory and gut microbiota composition. Male C57BL/6 mice were trained for 8 weeks starting at 14 months; age-matched controls remained sedentary. Swimming reduced weight gain and epididymal fat mass and progressively improved muscle strength and endurance. Exercised mice showed enhanced short-term spatial discrimination and long-term associative recognition in object location and object-in-place tasks without changes in locomotion or anxiety-like behavior. These cognitive benefits coincided with reduced circulating pro-inflammatory cytokines and a hippocampal shift toward a neuroprotective profile, with down-regulation of inflammatory and glial activation markers and up-regulation of brain-derived neurotrophic factor (BDNF). Muscle performance correlated positively with hippocampus-dependent memory, linking physical resilience to cognitive outcomes. In parallel, 16S rRNA gene sequencing revealed an exercise-induced remodeling of the gut microbiota, characterized by significant changes in community structure and coordinated shifts in the relative abundance of shared taxa. Exercise enriched genera associated with metabolic homeostasis and anti-inflammatory functions, including Akkermansia, Odoribacter and Alistipes, while reducing taxa more prevalent in sedentary animals, such as Romboutsia. Collectively, these findings demonstrate that moderate-intensity swimming initiated during late middle age concurrently improves physical performance, cognitive resilience, inflammatory status and gut microbiota composition, supporting exercise as a multi-system intervention associated with coordinated adaptations across the muscle-gut-brain axis during aging.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809251","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}