Aging and Disease最新文献_第2页

Brain Aging and the Pursuit of Longevity: Biological Mechanisms and Clinical Implications. 脑老化和对寿命的追求：生物学机制和临床意义。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-15 DOI: 10.14336/AD.2026.0269

Myung-Hoon Han, Shin-Woong Ko, Seong-Ho Koh

{"title":"Brain Aging and the Pursuit of Longevity: Biological Mechanisms and Clinical Implications.","authors":"Myung-Hoon Han, Shin-Woong Ko, Seong-Ho Koh","doi":"10.14336/AD.2026.0269","DOIUrl":"https://doi.org/10.14336/AD.2026.0269","url":null,"abstract":"Brain aging is an inevitable but modifiable process in which cellular, molecular, and systemic alterations converge on the central nervous system to determine cognitive health span. Much of the existing literature examines the biological mechanisms of aging, the distinction between normal and pathological brain aging, and lifestyle or pharmacological interventions as separate domains, with few integrative analyses connecting these elements into a clinically relevant conceptual framework. This knowledge gap limits the effective translation of geroscience advances into practical, lifespan-oriented strategies for prevention and care. This review aims to: (1) distinguish systemic aging from cognitive frailty within a brain-oriented clinical framework; (2) summarize key molecular mechanisms of brain aging, including telomere shortening, genomic instability, epigenetic alterations, loss of proteostasis, and mitochondrial dysfunction; (3) contrast clinical features of normal brain aging with neurodegenerative disease; and (4) evaluate emerging therapeutic strategies, including senolytics, gene modulation, and nutrient-sensing pathway regulation, while critically appraising the translational readiness of each. Integrating proactive lifestyle measures with advances in geroscience may provide a cohesive framework for promoting not only longer life but also healthier brain aging, although most interventional evidence to date remains preclinical, and substantial translational gaps must be addressed before these strategies can be validated in clinical practice.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809015","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}

引用次数: 0

Targeting Meningeal Lymphatic Vessels to Advance Stroke Therapy. 靶向脑膜淋巴管推进脑卒中治疗。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-15 DOI: 10.14336/AD.2026.0125

Yang Liu, Xiansheng Liu, Shihao Lin, Tao Lv, Zhi-Peng Xiao, Wenwu Liu, Heng Zhao, Shuang Liao, Xiaohua Zhang, Qin Hu

{"title":"Targeting Meningeal Lymphatic Vessels to Advance Stroke Therapy.","authors":"Yang Liu, Xiansheng Liu, Shihao Lin, Tao Lv, Zhi-Peng Xiao, Wenwu Liu, Heng Zhao, Shuang Liao, Xiaohua Zhang, Qin Hu","doi":"10.14336/AD.2026.0125","DOIUrl":"https://doi.org/10.14336/AD.2026.0125","url":null,"abstract":"Meningeal lymphatic vessels (mLVs) have recently emerged as pivotal regulators of central nervous system homeostasis, orchestrating cerebrospinal fluid (CSF) drainage, metabolic waste clearance, and neuroimmune surveillance at the brain and meningeal interface. Stroke, ischemic or hemorrhagic, exerts profound functional insults on mLVs, disrupting clearance pathways. These disturbances not only exacerbate acute edema and neuroinflammation but also dictate long-term outcomes, including post-stroke cognitive decline. In this review, we synthesize current understanding of mLVs anatomy and physiology, emphasizing their dynamic remodeling after stroke. We further examine the context-dependent immune functions of mLVs, and their role in shaping post-stroke brain injury and repair. In addition, we discuss emerging therapeutic strategies targeting the glymphatic-lymphatic axis and outline key translational challenges. Although these findings support a framework in which impaired fluid clearance contributes to stroke pathophysiology, most mechanistic insights derive from preclinical models, and direct evidence in human stroke remains limited. Accordingly, therapeutic implications should be interpreted with caution and require rigorous clinical validation.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809379","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}

引用次数: 0

Sex- and Age-Dependent Metabolic and Inflammatory Pathways in Cardiomyopathy: The Role of Sirtuins, Inflammaging and Mitochondrial Homeostasis. 心肌病中性别和年龄依赖的代谢和炎症途径：Sirtuins、炎症和线粒体稳态的作用。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-14 DOI: 10.14336/AD.2025.1591

Maria Luisa Barcena

{"title":"Sex- and Age-Dependent Metabolic and Inflammatory Pathways in Cardiomyopathy: The Role of Sirtuins, Inflammaging and Mitochondrial Homeostasis.","authors":"Maria Luisa Barcena","doi":"10.14336/AD.2025.1591","DOIUrl":"https://doi.org/10.14336/AD.2025.1591","url":null,"abstract":"Aging and biological sex modulate cardiomyopathy through interconnected metabolic, inflammatory and mitochondrial pathways. Aging impairs Sirt1/Sirt3-AMPK signaling, promotes low-grade inflammation and mitochondrial dysfunction, while sex hormones shape dimorphic resilience and vulnerability across the life course. In dilated cardiomyopathy (DCM) and inflammatory cardiomyopathy (DCMI), age aggravates Sirt1 loss, triggers compensatory AMPK activation and reduces mitochondrial proteins (TOM40/TIM23/SOD2), particularly in older men. In DCMI, Sirt1 levels stay stable but processes differ by sex. Older men show increased mitophagy; women have impaired biogenesis. Inflammaging with elevated NF-κB/IL-12 and macrophage infiltration is stronger in men. E2 suppresses NF-κB/ROS via ERα/β and promotes M2 polarization, whereas testosterone enhances PGC-1α-dependent metabolism but amplifies fibrosis. Collectively, these findings define an age-sex framework of cardiomyopathy vulnerability and support precision strategies targeting sirtuins, inflammasomes and hormone-related pathways to slow or modify disease progression.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147809364","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}

引用次数: 0

Extension of Lifespan and Amelioration of Alzheimer's Disease Phenotypes by Genetic Manipulation of Mitochondrial NAD⁺/NADH Ratio. 通过基因操作线粒体NAD+/NADH比率延长寿命和改善阿尔茨海默病表型。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-13 DOI: 10.14336/AD.2026.0011

Suman Rimal, Jae-Hyuk Lee, Yanzi He, Bingwei Lu

{"title":"Extension of Lifespan and Amelioration of Alzheimer's Disease Phenotypes by Genetic Manipulation of Mitochondrial NAD+/NADH Ratio.","authors":"Suman Rimal, Jae-Hyuk Lee, Yanzi He, Bingwei Lu","doi":"10.14336/AD.2026.0011","DOIUrl":"https://doi.org/10.14336/AD.2026.0011","url":null,"abstract":"Aging remains the most significant risk factor for common neurodegenerative diseases including Alzheimer's disease (AD). According to the geroscience hypothesis, aging is malleable and that by targeting basic aging physiology, we can alleviate many of the age-related chronic diseases. The common mechanisms driving aging and age-related diseases remain poorly defined. Mitochondrial dysfunction is recognized as a fundamental hallmark of aging, and recent studies implicate mitochondrial reverse electron transport (RET) as a driver of aging. The key outcomes of RET, increased ROS and decreased NAD+/NADH ratio, have both been associated with aging and age-related disease, but the causal relationship remains uncertain. Here we applied causal metabolism to test the role of mitochondrial NAD+/NADH in aging and AD, using Drosophila as a model system. By using a mitochondrial targeted version of Lactobacillus brevis NADH oxidase (LbNox) to boost mitochondrial NAD+/NADH ratio independent of the energy state of the cell, we found that increasing mitochondrial NAD+/NADH ratio in neuronal or muscle tissues is sufficient to extend lifespan. Moreover, boosting mitochondrial NAD+/NADH ratio is beneficial in two independent models of AD, rescuing the proteostasis failure, locomotor and cognitive deficits, and lifespan shortening in these models. Our results identify altered mitochondrial NAD+/NADH ratio as a major contributor to the biological effects of RET on aging and age-related diseases and a potential therapeutic target.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687556","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}

引用次数: 0

InflammAging and Human Diversity: Expanding Horizons in Age-Related Chronic Disease. 炎症和人类多样性：年龄相关慢性疾病的扩展视野。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-07 DOI: 10.14336/AD.2026.0077

José M Izquierdo

{"title":"InflammAging and Human Diversity: Expanding Horizons in Age-Related Chronic Disease.","authors":"José M Izquierdo","doi":"10.14336/AD.2026.0077","DOIUrl":"https://doi.org/10.14336/AD.2026.0077","url":null,"abstract":"InflammAging (IA) is a sterile, low-grade systemic inflammation characterizing human aging. This chronic inflammatory state, combining \"inflammation\" and \"aging\", drives the aging trajectory and associated pathology even in the absence of acute clinical signs. IA is a key etiological factor for numerous age-associated diseases, including neurodegeneration (e.g., Alzheimer's disease), cardiovascular disorders, diabetes, sarcopenia, cancer, frailty, and multimorbidity, by exacerbating tissue/organ damage and impairing endogenous repair. Historically viewed as a universal hallmark of aging, this concept is now being refined. Current research highlights how human diversity-encompassing genetic, ethnic, gender, sex, environmental, socioeconomic, and lifestyle variations-could modulate the expression and severity of IA. This interplay, as emerging hypotheses, represents a new horizon in gerontology and chronic diseases, necessitating a potential paradigm shift from a one-size-fits-all model to personalized, population-specific approaches. This evolving nuanced understanding might be crucial for the successful implementation of precision medicine and for advancing global health strategies targeting age-related chronic diseases.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687569","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}

引用次数: 0

Dietary Interventions for Healthy Aging: An Epigenetic Perspective. 饮食干预健康老龄化：一个表观遗传学的观点。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-06 DOI: 10.14336/AD.2026.0333

Xinyu Zhang, Ziyue Xie, Huimin Bian, Yu Li, Ruigong Zhu, Jia Sun

引用次数: 0

Fine-Tuning Autophagy in Skeletal Muscle: From Homeostasis to Muscle Wasting Disorders. 骨骼肌的微调自噬：从稳态到肌肉萎缩障碍。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-03 DOI: 10.14336/AD.2026.0170

Qian Gou, Shi Chee Ong, Wen Xing Lee, Priya D Gopal Krishnan, Hong-Wen Tang

{"title":"Fine-Tuning Autophagy in Skeletal Muscle: From Homeostasis to Muscle Wasting Disorders.","authors":"Qian Gou, Shi Chee Ong, Wen Xing Lee, Priya D Gopal Krishnan, Hong-Wen Tang","doi":"10.14336/AD.2026.0170","DOIUrl":"https://doi.org/10.14336/AD.2026.0170","url":null,"abstract":"Skeletal muscle homeostasis and regenerative capacity depend on efficient protein turnover, organelle quality control, and metabolic adaptation. Disruption of these processes contributes to muscle atrophy and functional decline during aging and various pathological conditions. Autophagy, a lysosome-dependent degradative pathway, maintains muscle integrity by clearing damaged proteins and organelles, preserving mitochondrial quality, and supporting muscle stem cell (MuSC) function. Both insufficient and excessive autophagy are detrimental: reduced flux impairs proteostasis, mitochondrial function, and regeneration, whereas hyperactivation drives excessive protein degradation, mitochondrial loss, and muscle wasting under stress. This review discusses molecular mechanisms regulating autophagy in skeletal muscle, including nutrient- and energy-sensing pathways (AMPK and mTORC1), transcriptional control of autophagy and lysosomal genes, and mitochondrial modulators. Evidence from genetic models and disease contexts indicates that both insufficient and excessive autophagy are associated with muscle degeneration, highlighting the need for balanced autophagic control rather than simple activation or inhibition. Together, these observations support a conceptual framework in which skeletal muscle health depends on maintaining autophagic activity within a context-dependent functional range, although this range is not yet quantitatively defined. This framework provides a useful basis for considering therapeutic strategies targeting muscle wasting.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687535","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}

引用次数: 0

MAMs as a promising therapeutic strategy for age-related neurodegenerative diseases. MAMs作为一种治疗与年龄相关的神经退行性疾病的有前途的策略。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-02 DOI: 10.14336/AD.2025.1342

Giacoma Galizzi

{"title":"MAMs as a promising therapeutic strategy for age-related neurodegenerative diseases.","authors":"Giacoma Galizzi","doi":"10.14336/AD.2025.1342","DOIUrl":"https://doi.org/10.14336/AD.2025.1342","url":null,"abstract":"Aging is a natural process leading to the slow and progressive deterioration of numerous physiological functions. It is the main risk factor for several neurodegenerative diseases. Mitochondria-associated membranes (MAMs) or mitochondria-ER contacts (MERCs) are essential and dynamic sites of contact between mitochondria and the endoplasmic reticulum (ER) and are involved in numerous cellular processes, such as calcium (Ca2+) homeostasis, reactive oxygen species (ROS) production, autophagy, inflammation, mitochondrial dynamics, apoptosis, lipid biosynthesis, and trafficking. As a result, they play a significant role in maintaining cellular functionality regulating metabolism and ensuring proper stress responses. Recently, MAMs have been widely investigated to understand their critical role in cell physiology as well as in different pathological conditions. Increasing evidence indicates that alterations in ER-mitochondria communication contribute to aging and the development of age-related diseases. However, the cellular mechanisms underlying this link remain unclear. Understanding how these interactions change with age could provide further insights into the aging process and the mechanisms underlying age-related diseases, suggesting potential new therapeutic strategies. This review summarizes the current knowledge on MAM biology, focusing on their role in the pathogenesis of age-related brain disorders. Their therapeutic potential in limiting the progression of some neurodegenerative disorders such as Alzheimer's disease, Parkinson's disease and amyotrophic lateral sclerosis, and slowing the physiological aging process are also explored.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687586","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}

引用次数: 0

The Lung-Brain Axis in Cognitive Impairment and Dementia: Mechanisms and Therapeutic Prospects. 认知障碍和痴呆的肺脑轴：机制和治疗前景。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-02 DOI: 10.14336/AD.2026.0095

Liying Zhang, Abigail Dove, Juan Du, Dan Yang, Qiaoli Su, Xiaoli Huang, Jiao Wang, Jirong Yue

引用次数: 0

Clock and the Cleaner: Circadian Rhythms and Autophagy Coupling in Alzheimer's Disease. 时钟和清洁工：阿尔茨海默病的昼夜节律和自噬耦合。

IF 6.9 2区医学

Aging and Disease Pub Date : 2026-04-02 DOI: 10.14336/AD.2025.1496

Liyun Ma, Zhenxiang Gong, Rong Gao, Lina Zhu, Liru Wu, Min Zhang, Li Ba

{"title":"Clock and the Cleaner: Circadian Rhythms and Autophagy Coupling in Alzheimer's Disease.","authors":"Liyun Ma, Zhenxiang Gong, Rong Gao, Lina Zhu, Liru Wu, Min Zhang, Li Ba","doi":"10.14336/AD.2025.1496","DOIUrl":"https://doi.org/10.14336/AD.2025.1496","url":null,"abstract":"Alzheimer's disease (AD) continues to progress despite decades of research on protein aggregation, highlighting the need to understand upstream homeostatic failures. Among the earliest alterations in AD are disruptions of circadian rhythms and autophagy, which are mechanistically intertwined. Although circadian dysfunction and autophagic failure have been studied separately, the stage-dependent, region-specific, and cell-type-specific interplay between these systems remains poorly integrated, limiting the development of targeted interventions. In a healthy brain, the circadian clock and autophagy mutually interact, maintaining proteostasis, neuronal function, and rhythmic metabolic and immune processes. In early-stage AD, circadian rhythms show mild disruption and autophagy initiation remains active, but downstream autophagosome-lysosome fusion and lysosomal degradation are impaired, leading to the accumulation of AD pathological proteins. Dysregulation is cell-type-specific: neuronal clocks remain relatively intact, whereas astrocytic and microglial clocks exhibit altered metabolic and immune rhythms, contributing to early pathogenic events. In late-stage AD, severe circadian disruption likely uncouples circadian control from autophagy, and these dysfunctions mutually exacerbate each other, driving neuroinflammation, neuronal dysfunction, and further accumulation of pathological proteins. This review synthesizes current evidence on the circadian-autophagy axis, highlighting mechanistic insights and therapeutic opportunities, and emphasizes the importance of integrating stage-, region-, and cell-type-specific dynamics for the development of precise interventions in AD.","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-04-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147687447","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}

引用次数: 0