Aging and Disease最新文献

{"title":"Functional Imaging in Osteoarthritis: Bridging Mechanistic Insight and Therapeutic Translation.","authors":"Xiwei Fan, Fumin Yuan, Feng Gao, Chaoshuo Liu, Indira Prasadam, Antonia Rujia Sun, Ross Crawford, Yanping Wang, Siyi Chen, Qichen Long, Xinzhan Mao","doi":"10.14336/AD.2026.0304","DOIUrl":"https://doi.org/10.14336/AD.2026.0304","url":null,"abstract":"<p><p>Functional imaging provides a decision-oriented framework for evaluating osteoarthritis (OA) beyond late structural morphology. OA is a heterogeneous, aging-associated whole-joint disease in which cartilage matrix disruption, synovial inflammation, subchondral bone remodelling, altered mechanics, and pain-circuitry changes may evolve before radiographic end-stage features dominate. Conventional radiography and symptom scores remain indispensable, but they provide limited information about active biological processes and are often poorly aligned with pain, progression risk, or treatment response. In this Perspective, we argue that functional imaging should be selected according to a defined decision context rather than technical novelty alone. Quantitative and compositional magnetic resonance imaging (MRI), dynamic contrast-enhanced MRI, selected positron emission tomography (PET)-based approaches, procedure-linked optical coherence tomography, neurofunctional imaging, mass spectrometry imaging, and isotope-informed spatial methods occupy different positions along the translational pathway. Near-term clinical and trial value is most plausible for risk enrichment, mechanistic phenotyping, longitudinal monitoring, and target-engagement assessment; discovery platforms remain essential for target nomination and endotype refinement. We therefore propose a restrained roadmap that separates candidate signals from qualified biomarkers and prioritises reproducibility, biological specificity, and clinical utility.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597378","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-Related Metaflammation and Mitochondrial Dysfunction in Neurodegenerative Diseases.","authors":"Wenting Gao, Hye-Yeon Lee, Kyung-Jin Min","doi":"10.14336/AD.2026.0366","DOIUrl":"https://doi.org/10.14336/AD.2026.0366","url":null,"abstract":"<p><p>Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS) are increasingly recognized as manifestations of aging-associated systemic dysfunction, rather than isolated brain disorders. Central to this dysfunction is the interplay among metaflammation, mitochondrial breakdown, and chronic neuroinflammation. Metaflammation, driven by peripheral metabolic stress, may prime the brain's immune environment through cytokine signaling and blood-brain barrier compromise. This metabolic-inflammatory crosstalk is thought to impair mitochondrial integrity in neurons and glial cells, promoting oxidative stress and the release of pro-inflammatory mitochondrial components. These mitochondrial signals, in turn, may activate microglial and astrocytic innate immune responses, creating a potentially self-reinforcing cycle of neuroinflammation and energy failure that may contribute to neuronal loss. This review outlines a proposed framework linking metaflammation to neurodegeneration, emphasizing shared mechanisms across AD, PD, and ALS. We further examine preclinical and clinical advances in therapeutic strategies that target this axis including anti-inflammatory agents, caloric restriction, mitophagy enhancers, mitochondrial antioxidants, and senescence-targeted therapies. Together, these interventions reflect a shift from symptom management to systemic metabolic and immune modulation, offering a unified framework for understanding and potentially influencing age-related neurodegeneration.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597655","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":"From Structure to Function: Cognitive Impairment and Its Heterogeneity in Cerebral Small Vessel Disease.","authors":"Wei Sun, Aini He, Benke Zhao, Xuefan Yao, Xiao Wu, Haiqing Song","doi":"10.14336/AD.2026.0351","DOIUrl":"https://doi.org/10.14336/AD.2026.0351","url":null,"abstract":"<p><p>Cerebral small vessel disease (CSVD) is a common, age-related microvascular brain disorder and a major vascular cause of cognitive impairment. However, individuals with similar magnetic resonance imaging (MRI) lesion burdens often follow different cognitive trajectories, indicating that conventional imaging captures only late-stage manifestations of a broader pathological cascade. This review focuses on cognitive heterogeneity in CSVD through a heterogeneity-oriented conceptual framework, discussing how divergent cognitive trajectories may arise through the interaction of lesion-related factors, network-mediated consequences, biological and pathological modifiers, and individual susceptibility factors. We highlight the importance of lesion topography, particularly damage to strategic network hubs and connections. Beyond focal lesions, structural network disruption and remote structural and functional abnormalities beyond MRI-visible lesions further shape clinical heterogeneity. We additionally examine biological and pathological modifiers, including molecular biomarkers, heterogeneous neuropathological substrates, and mixed pathology, as well as individual susceptibility factors, such as life-course influences, brain reserve, and resilience. Together, these interacting mechanisms help explain why individuals with comparable structural lesion burdens may experience divergent cognitive trajectories. By reframing CSVD-related cognitive impairment beyond a simple lesion-burden model, this review highlights implications for diagnosis, prognostication, and future individualized approaches to cognitive impairment in CSVD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597410","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-Cell RNA Sequencing Characterizes Microglial Phenotypic Heterogeneity Across Different Stroke Subtypes.","authors":"Yiyan Guo, Tongtong Xu, Chang Liu, Shiyu Deng, Lin Gan, Qianyuan Lian, Jing Ye, Wanlu Li, Zhijun Zhang, Guo-Yuan Yang, Jixian Wang, Yaohui Tang","doi":"10.14336/AD.2026.0803","DOIUrl":"https://doi.org/10.14336/AD.2026.0803","url":null,"abstract":"<p><p>Microglia-mediated neuroinflammation is a key contributor to secondary brain injury across diverse cerebrovascular pathologies, yet the precise transcriptomic diversity and temporal evolution of microglial states across different stroke subtypes remain to be fully elucidated. We utilized single-cell RNA sequencing to profile the temporal transcriptomic landscape of the immune microenvironment in mouse models of ischemic stroke (IS), hemorrhagic stroke (HS), and chronic cerebral hypoperfusion (CCH) at 3, 7 and 14 days post-injury. Our data showed a \"temporal mismatch\" in immunological trajectories between acute and chronic insults. Specifically, IS and HS triggered an immediate, burst-like microglial activation as early as 3 days, the CCH model exhibited a significant latency window, maintaining a predominantly homeostatic profile until a profound transcriptomic transition toward active phenotypes occurred at 14 days. Notably, we identified a prominent S100A8⁺/CHIL3⁺ inflammatory cluster enriched during the hyperacute phase of HS, which may represent an early inflammatory signature associated with intraparenchymal hemorrhage. Interestingly, despite these early divergent responses, the 14-day microglial landscapes across the three models showed a putative shared chronic activation pattern characterized by SPP1⁺ DAM-like signatures and MHC-II-associated antigen-presentation features. Furthermore, we identified a pre-existing stress-responsive signature (Hspa1a⁺/ Hspa1b⁺) in steady-state white matter microglia. These findings provide a high-resolution roadmap of the divergent and convergent immune signatures across cerebrovascular disease spectra, offering hypothesis-generating insights for the development of stage-specific and etiology-tailored immunotherapeutic interventions. Overall, our pooled-library scRNA-seq analysis provides a descriptive and hypothesis-generating framework for stroke-associated microglial and supported by selected tissue-level validation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148597521","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":"Metabolism of Young and Aged Hematopoietic and Acute Myeloid Leukemia Stem Cells: Insights for Rejuvenation and Therapy.","authors":"Alhomidi Almotiri","doi":"10.14336/AD.2026.0302","DOIUrl":"https://doi.org/10.14336/AD.2026.0302","url":null,"abstract":"<p><p>Hematopoietic stem cells (HSCs) reside in the adult bone marrow and sustain the lifelong production of blood and immune cells. The processes of HSC quiescence, activation, and aging are complex and are orchestrated by a combination of intrinsic and extrinsic stimuli. Similarly, leukemic stem cells (LSCs) are responsible for the initiation of leukemia and drug resistance. Metabolic adaptations are critical for these processes, and research in this area is rapidly evolving. In this review, the metabolic programs, including glycolysis, mitochondrial metabolism, and amino acid and lipid metabolism, of young HSCs, aged HSCs, leukemia blasts, and LSCs are comparatively presented, with a greater focus on aged HSCs and LSCs, as aging and leukemia represent substantial health challenges. The clinical implications of metabolic vulnerabilities, either for rejuvenating aged HSCs or selectively killing LSCs, are also discussed.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350290","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":"Vitamin C, ACSL4, and Ferro-Aging: Mechanistic Insights and Translational Perspectives from Primate Studies.","authors":"Chenxi Li, Zhongcheng Gong, Jishi Ye, Yuchen Ni","doi":"10.14336/AD.2026.0371","DOIUrl":"https://doi.org/10.14336/AD.2026.0371","url":null,"abstract":"<p><p>The concept of ferro-aging has been proposed as an evolutionarily conserved, iron-driven aging trajectory orchestrated by acyl-coenzyme A (CoA) synthetase long-chain family member 4 (ACSL4), which links lipid peroxidation, cellular senescence, and systemic organ decline in primates. Emerging evidence from non-human primate studies suggests that vitamin C (VC), traditionally viewed as a broad-spectrum antioxidant, has been proposed to interact with and inhibit ACSL4 activity at supraphysiological concentrations, potentially reversing multi-omic markers of biological age and preserving neural architecture, functional connectivity, and metabolic homeostasis in aged individuals. However, the precise molecular mechanism of VC-mediated ACSL4 inhibition remains unconfirmed, and the geroprotective efficacy of VC in humans is yet to be validated. This Perspectives critically critically discusses the mechanistic underpinnings of the VC-ACSL4-ferro-aging axis, examines key limitations of current evidence, and highlights the translational potential and unresolved challenges of targeting ferro-aging for promoting healthy aging.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350281","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":"Chronogeroprotection: Circadian Action Bundles for Healthy Aging.","authors":"Jasmin Weninger, Shadab Rahman, Mustafa Özcürümez","doi":"10.14336/AD.2026.0646","DOIUrl":"https://doi.org/10.14336/AD.2026.0646","url":null,"abstract":"<p><p>Aging is a multidimensional biological process characterized by a progressive decline in physiological resilience to stressors, shaped by molecular dysregulation and cumulative behavioral and environmental challenges, and accompanied by an increased risk of disease. Despite advances in geroscience, biological time remains underused in prevention, clinical care, and public-health strategy. Here we propose chronogeroprotection as a novel circadian-informed perspective on the preservation of physiological resilience across the life span. We synthesize evidence showing that circadian regulation coordinates near-24-hour rhythms in metabolism, immune function, DNA repair, and sleep-wake regulation, thereby influencing vulnerability to age-related diseases. We then translate these insights into a prevention-oriented model for healthy aging. We suggest that chronogeroprotective action bundles, which consist of interventions, properly synchronized to light exposure, sleep, meal timing, physical activity, pharmacology, diagnostics, and patient care workflows according to biological time, will help bridge the hallmarks of aging and healthcare system redesign. Through integration of circadian principles into diagnostic procedures, electronic health records, clinical workflows, educational programs, research networks, and public-health policy, biological time can become a tangible preventive and therapeutic factor relevant for healthy aging consistent with the WHO Decade of Healthy Ageing priorities.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350211","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":"Staging of Neuropil Morphological Alterations in Alzheimer's Disease.","authors":"Zhi-Yi Zhang, Xin-Meng Wang, Xin Ma, Yi Wang, Shuai-Deng Wang, Yi-Lin Peng, Kun Cheng, Yue-Ru Shen, Guo-Zhang Tang, Chen-Wei Wang, Jiang-Ning Zhou","doi":"10.14336/AD.2026.0213","DOIUrl":"https://doi.org/10.14336/AD.2026.0213","url":null,"abstract":"<p><p>Alzheimer's disease (AD) involves the progressive fragmentation of neural connectivity. This study aims to investigate the morphological degeneration of neuropil fibers in AD and evaluate their utility as a marker for pathological severity. Post-mortem brain tissues from 92 cases across eight distinct regions were analyzed. We used Bielschowsky silver staining with automated quantitative morphometry to measure neuritic fiber length and curvature in the neuropil, and immunofluorescence to detect neurite cytoskeletal markers. Finally, a novel histological staging system for neuropil disruption was established to assess disease progression. Morphometric analysis revealed progressive reductions in neuritic fiber length and increased curvature tracking with disease severity, a significant negative correlation confirmed these are coupled degenerative manifestations. Immunofluorescence demonstrated extensive cytoskeletal fragmentation that corresponded to the pattern observed with silver staining. Based on morphometric analysis, a novel four-tier staging system was established, defined neuropil by homogeneous compactness (-), initial (+), extensive (++) disruption, and complete fragmentation (+++), which correlated preferentially with Phospho-Tau load. Crucially, subtle neuropil alterations were detectable in the entorhinal cortex, amygdala, and anterior hippocampus even in Braak 0 stage, suggesting a potential association between these early changes and the initial stages of tau pathogenesis. This study establishes a staging system for assessing neuropil degeneration, demonstrating that neuropil fragmentation and geometric distortion are candidate AD pathological markers. By systematically analyzing neuritic fiber morphology and proposing a neuropil disruption stage, this work provides critical insights into early AD pathogenesis, offering a foundation for future diagnostic strategies pending validation in independent cohorts with clinical correlations.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350346","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 Cellular Senescence as a Therapeutic Strategy to Attenuate Pulmonary Fibrosis Associated with Metabolic Syndrome.","authors":"Michaela Rennerova, Tereza Havrlantova, Igor Simonik, Renata Pavlovicova, Miloslava Cechova, Anna Cinkajzlova, Dan-Diem Thi Le, Jana Klouckova, Jiri Fronek, Filip Thieme, Jiri Neuzil, Lukas Werner, Jan Stursa, Milos Mraz, Martin Haluzik, Sona Stemberkova Hubackova","doi":"10.14336/AD.2026.0150","DOIUrl":"https://doi.org/10.14336/AD.2026.0150","url":null,"abstract":"<p><p>Metabolic dysfunction, in particular obesity and type 2 diabetes mellitus, increases susceptibility to pulmonary fibrosis via chronic inflammation, oxidative stress, and the accumulation of senescence. Senescent cells promote secretion of pro-fibrotic mediators that impair lung structure and repair. Here, we investigated whether reducing senescent cell burden using the mitochondria-targeted senolytic agent MitoTam, or weight-loss-induced improvement after bariatric surgery, can attenuate metabolic-associated pulmonary injury. In mice with diet-induced obesity, MitoTam improved glucose homeostasis, reduced adiposity, and markedly decreased senescence markers in lungs. This was accompanied by reduced inflammatory and fibrotic gene expression, diminished myofibroblast accumulation, and alleviated lung hypoxia. MitoTam also lowered senescence and expression of key pro-fibrotic factors, including GDF15, FGF2, TGFβ, and endothelin-1 (EDN1) in subcutaneous adipose tissue, indicating both direct pulmonary and systemic endocrine effects. In patients with class III obesity, laparoscopic sleeve gastrectomy induced substantial body weight loss, improved metabolic parameters, and significantly reduced adipose tissue senescence and pro-fibrotic signaling, including EDN1 expression and its level in the circulation. These findings identify cellular senescence as a modifiable driver linking metabolic dysfunction to pulmonary fibrosis and highlight mitochondria-targeted senolysis with MitoTam as a promising therapeutic approach.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350368","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":"Lifelong Consumption of Freeze-Dried Parabacteroides Distasonis Improves Gut Barrier Integrity and Extends Lifespan and Health Span in Drosophila Melanogaster.","authors":"Sarah Shnayder, Vicki Do, Junyue Wang, Luana Machado, Sofia Rosa, Lora Kusaku, Benjamin Kuo, Jill Hutchinson, Grace Ogden, Neja Majeti, Weimin Guo, Samuel Beck, Mitch McVey, Jimmy W Crott","doi":"10.14336/AD.2025.1584","DOIUrl":"10.14336/AD.2025.1584","url":null,"abstract":"<p><p>Chronic inflammation has been shown to be associated with aging. In Drosophila melanogaster, age-related inflammation in the gut results in a disruption of gut barrier integrity, which can lead to reduced intestinal function and death. The anaerobic bacterium Parabacteroides distasonis (Pd) has anti-inflammatory properties and can attenuate tumorigenesis and promote intestinal barrier integrity in a mouse model of colorectal cancer. Here, we show that administration of Pd to adult Drosophila significantly increases median lifespan and promotes maintenance of climbing ability throughout adult life. Furthermore, Pd supplementation enhances gut barrier integrity in aged adults. RNA-Seq analysis of adult gut tissue revealed that the elevated healthspan in Pd supplemented flies is accompanied by transcriptional upregulation of genes involved in DNA replication and maintenance of genome integrity. These results suggest that Pd supplementation may induce a transcriptional shift towards augmented DNA repair in the aging gut that prevents the breakdown of gut barrier integrity and promotes healthy aging.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350320","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}