Aging and Disease最新文献

{"title":"Circadian Rhythms, Metabolic Disorders, and Cardiovascular Aging: Molecular Crosstalk and Clinical Translation.","authors":"Jing Wang, Qianwen Xu, Dongchen Zhou, Biqi Zhang, Xiaosheng Hu, Ting Chen","doi":"10.14336/AD.2026.0314","DOIUrl":"https://doi.org/10.14336/AD.2026.0314","url":null,"abstract":"<p><p>Circadian rhythms play a crucial role in regulating physiological processes, and disruptions caused by aging, shift work, or irregular schedules are closely associated with metabolic dysfunction and accelerated cardiovascular aging. Age-related declines in circadian clock function contribute to metabolic imbalances and cardiovascular decline through pathways involving inflammation, oxidative stress, and mitochondrial dysfunction. Research has identified complex molecular networks linking circadian dysregulation to metabolic disorders and cardiovascular diseases, highlighting potential therapeutic targets such as sirtuin 1, peroxisome proliferator-activated receptor α, and reverse erythroblastosis virus α. Interventions based on circadian principles-such as time-restricted eating, chronotherapy, lifestyle modifications, and light therapy-exhibit promise in mitigating cardiovascular aging. However, several of these strategies require further validation in older adults, and challenges persist in clinical implementation owing to a lack of large-scale trials, population diversity, and real-world barriers. This review synthesizes current mechanistic evidence and underscores the necessity for personalized circadian-based approaches to enhance cardiovascular health in aging populations.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248706","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 Dynamics in Cellular Senescence: Mechanisms, Context Dependence, and Therapeutic Potential.","authors":"Dan Wu, Shihao Jiang, Chenyang Li, Xianqi Wang, Yuexiang Ma, Peiwen Wang, Yanan Xu, Heliang Fu, Qianmei Wang, Kuo Shen, Rui Zheng, Junjie Li","doi":"10.14336/AD.2026.0323","DOIUrl":"https://doi.org/10.14336/AD.2026.0323","url":null,"abstract":"<p><p>Mitochondria function as the primary energy centers of cells, and the dynamic equilibrium between their fission and fusion is essential for preserving cellular functional integrity and metabolic homeostasis. As research in cell biology has advanced, an imbalance in mitochondrial dynamics is tightly and bidirectionally linked to cellular aging. It not only contributes to aging-related functional decline but is also exacerbated by the senescent state itself, creating a vicious cycle that impacts key biological processes. Recent studies have demonstrated that the disruption of mitochondrial fission and fusion during aging, through mechanisms such as impaired cellular energy metabolism, increased oxidative stress, compromised mitophagy, and the induction of senescence-associated secretory phenotypes, collectively accelerates the functional decline of cells and organs. Nonetheless, many questions remain regarding the specific regulatory network of mitochondrial dynamics and its variations across different stages of aging. The aim of this review is to systematically elucidate the fundamental role of imbalances in mitochondrial dynamics in the context of cellular aging, along with its underlying molecular mechanisms. This review summarizes various intervention strategies targeting this process, including targeted therapies, small molecule regulators, stem cell therapy, lifestyle modifications, and innovative mitochondrial transplantation technology, whereas these approaches are still in experimental or early-stage development, and their translational potential requires further validation. The ultimate objective is to offer novel theoretical insights and potential therapeutic approaches for mitigating aging and associated diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248771","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":"Epigenetic Clocks in the Cosmic Silence of a Deep Underground Laboratory: Implications for Aging and Space Exploration.","authors":"Javier A Menendez, Carlos Peña-Garay, Tomás Alarcón, Elisabet Cuyàs","doi":"10.14336/AD.2026.0468","DOIUrl":"https://doi.org/10.14336/AD.2026.0468","url":null,"abstract":"<p><p>DNA methylation aging clocks are among the most accurate biomarkers of chronological and biological age, yet why the methylome encodes time with reproducible precision remains unclear. Current models emphasize developmental patterning, imperfect epigenetic maintenance, chromatin drift, and remodeling associated with DNA repair. However, they do not consider whether the persistent physical noise from Earth's radiation environment contributes to clock variance or coherence. Here, we propose DEEP-CLOCK, an experimental framework that uses the deep underground laboratory (LSC-DUL) at Canfranc (Spain) as a natural protector from a primary external stochastic input, namely surface-level cosmic-ray muons. DULs suppress the muon component of cosmic-ray background radiation by several orders of magnitude without eliminating endogenous biochemical noise and other radiation sources. This enables DNA methylation clocks to be interrogated as noise-limited biosensors by measuring mean epigenetic-age trajectories, clock-CpG variance, and methylation entropy under matched underground and above-ground conditions. Two outcomes are envisioned. Muon depletion may narrow clock variance while preserving the mean trajectory, which is consistent with improved timekeeping precision. Alternatively, muon depletion could reveal structured drift, altered slopes, or metastable offsets, suggesting that extreme radiobiological quietness could destabilize clock coherence. Neither outcome would by itself imply slowed aging, rejuvenation, or improved function alone. However, DEEP-CLOCK will test whether epigenetic clock behavior is fully intrinsic or partly calibrated by chronic low-dose radiobiological background. This reductionist framework could clarify the physical constraints on epigenetic timekeeping and inform how aging clocks function in shielded terrestrial, lunar, and Martian habitats during aging, disease, and future space habitation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248678","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":"Cognitive Frailty in Older Adults with Ischemic Stroke: Epidemiology, Mechanisms, and Multidimensional Management Strategies.","authors":"Yang Li, Xiaoxing Lai, Wanchen Song, Kexin Zhang, Donglei Shi, Zhiyuan Zhang","doi":"10.14336/AD.2026.0305","DOIUrl":"https://doi.org/10.14336/AD.2026.0305","url":null,"abstract":"<p><p>As global population aging accelerates, the number of older adults with ischemic stroke (IS) continues to rise. Cognitive frailty (CF), a geriatric syndrome, exhibits relatively high prevalence in this population and is associated with substantially elevated risks of disability, mortality, and poor prognosis. This review summarizes the epidemiological characteristics, underlying pathological mechanisms, and key influencing factors of CF in older patients with IS, and proposes a personalized prevention and management framework guided by digital and intelligent technologies through multidisciplinary collaboration. The aim is to provide a robust theoretical foundation and practical guidance for early identification and precise intervention targeting CF in older adults with IS. With the caveat that current evidence is constrained by regional concentration and heterogeneity in CF definitions and assessment tools, pending prospective validation through standardized protocols.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248699","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":"Optimizing Antibody-Based Therapies for Alzheimer's Disease: From Clinical Limitations to Molecular Engineering Innovations.","authors":"Qian Liu, Rong-Rong Lin","doi":"10.14336/AD.2026.0292","DOIUrl":"https://doi.org/10.14336/AD.2026.0292","url":null,"abstract":"<p><p>Antibody-based immunotherapy represents one of the most promising disease-modifying strategies for Alzheimer's disease (AD). Recent anti-amyloid-β (Aβ) antibodies have achieved robust plaque clearance and modest cognitive benefits in early AD, establishing clinical proof of concept. However, limited efficacy and safety concerns, particularly amyloid-related imaging abnormalities (ARIA), continue to restrict their therapeutic potential. This review outlines the current clinical status of antibody therapies targeting Aβ, tau, and neuroinflammatory pathways, and summarizes key antibody optimization strategies, including aggregation-state-selective targeting, Fc engineering, brain shuttle technologies, nanobody platforms, and nanotechnology-enabled delivery. We further discuss emerging concepts from tumor immunotherapy, such as antibody-guided protein degradation and conditionally active biologics, as potential avenues for next-generation AD treatment.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248753","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":"Delphi-derived Framework for Healthspan-Oriented Care: The Cardiometabolic Health Perspective.","authors":"Marek Postula, Svjatoslavs Kistkins, Anna Nowak-Szwed, Salvatore DeRosa, Karol Kaminski, Anna Erat, Uģis Klētnieks, Othmar Moser, Dmitrijs Bliznuks, Ilia Stambler, Emīls Sjundjukovs, Jaron Rabinovici, Morten Scheibye-Knudsen, Alex Zhavoronkov, Vadim N Gladyshev, Steve Horvath, Bruno Vellas, George A Kuchel, Harald Sourij, Evelyne Bischof, Andreas F H Pfeiffer","doi":"10.14336/AD.2026.0279","DOIUrl":"https://doi.org/10.14336/AD.2026.0279","url":null,"abstract":"<p><p>This Delphi-derived expert consensus provides a clinical framework to optimize and maintain healthspan along the lifespan from the cardiometabolic health perspective in both healthy individuals and individuals with well-controlled cardiometabolic diseases. The framework guides the shaping of the evidence base in the clinical approach for assessing and targeting intrinsic capacity and healthspan. This approach integrates well-established cardiometabolic guidelines with the innovative and rapidly developing field of healthspan medicine. Recommendations were developed through a literature review and structured Delphi consensus. To ensure methodological rigor, recommendations were developed using a grading framework adapted from AHA/ESC guidelines. This system applied standardized Classes of Recommendation (I, IIa-c, III) and added novel Class IIc to designate interventions with uncertain or minimal benefit, supported by limited or inconclusive evidence. Evidence levels ranged from multiple RCTs/meta-analyses (A) to single RCTs or non-RCT studies (B) to expert consensus (C). Such an approach is a crucial step toward building both evidence and credibility for clinical strategies aimed at preserving healthspan-specifically by preventing cardiometabolic pathological aging and the associated decline in intrinsic capacity. The healthspan-oriented care framework defines healthy aging from a cardiometabolic perspective, classifying individuals into \"healthy aging without CMD\" and \"healthy aging with well-controlled CMD\" based on clinical, laboratory, and functional criteria. The framework also evaluates emerging diagnostic tools and their role in risk stratification. While emerging approaches show considerable promise, their clinical translation requires further validation, standardization, and large-scale evidence. This Delphi-derived expert consensus outlines a comprehensive framework for the cardiometabolic healthspan-oriented model of care by integrating evidence-based clinical criteria, functional assessments, and emerging geroscience insights.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248686","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":"Brain Dysfunction in Genetically Determined Accelerated Aging Syndromes.","authors":"Jelena Vasilevska, Nelli A Arakelyan, Anastasiya L Kungurtseva, Alisa V Vitebskaya, Evgeny I Rogaev","doi":"10.14336/AD.2026.0370","DOIUrl":"https://doi.org/10.14336/AD.2026.0370","url":null,"abstract":"<p><p>Human progeroid syndromes, caused by single-gene mutations, offer unique insights into the genetic determinants of brain development, ageing, and neurodegeneration. However, the link between these mutations and neurological phenotypes remains poorly understood. This integrative translational review synthesizes clinical, neuroimaging, cognitive, and experimental data across DNA repair disorders, RecQ helicase-associated syndromes, laminopathies, and other rare conditions. We propose a working hypothesis: severe, primary neurodegeneration occurs most consistently when the mutant gene is functionally expressed in post-mitotic neurons, as seen in DNA repair disorders. However, exceptions and complexities exist. Neurological phenotypes can also arise secondarily from glial dysfunction (e.g., Penttinen syndrome), vascular pathology (e.g., strokes in Hutchinson-Gilford progeria), or systemic disease. Furthermore, neuron-specific protective mechanisms, such as miR-9-mediated silencing of progerin, can uncouple systemic ageing from brain ageing. Current animal models often fail to replicate human gene expression patterns and neuropathology, limiting translational utility. This framework integrates clinical observations with biological mechanisms, supporting practical monitoring strategies while emphasising the need for human-relevant models to clarify how genetic mutations lead to brain dysfunction.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155164","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 Biomarkers in Osteoporosis: A Systematic Review of Molecular Mechanisms, Biological Aging, and Population Evidence.","authors":"Miaosen Liu, Su Yon Jung","doi":"10.14336/AD.2025.1653","DOIUrl":"https://doi.org/10.14336/AD.2025.1653","url":null,"abstract":"<p><p>While chronological age is an important risk factor for osteoporosis, biological aging measures may better capture nuances in systemic and bone-tissue aging among same-age individuals. This review aims to summarize the associations between DNA methylation/telomere dysfunction (mainly telomere shortening) and bone health. We searched for human epidemiological studies that examined the associations between blood-based epigenetic aging clocks or leukocyte telomere length (LTL) and osteoporosis-related outcomes on PubMed and Embase. Five epigenetic aging-related studies and 14 LTL-related studies were eventually included, from which data on study design, population, bone health-related outcomes, and statistically significant effect estimates were extracted. Risk of bias was assessed using the Newcastle-Ottawa Scale for observational studies. Findings were summarized narratively due to heterogeneity in study design, biomarkers, and outcome definitions. This review concludes that while laboratory-based studies often provide evidence of aging biomarkers' association with bone outcomes, population-level epidemiological studies provide inconclusive evidence, highlighting limited studies on epigenetic aging clocks and bone health, and inconsistent findings regarding the association between LTL and bone health. Challenges many of the human studies faced include small sample sizes, inadequate study designs, non-diverse cohorts, and heterogeneity in epigenetic clock selection and/or bone health outcomes. Future research should focus on conducting prospective studies with larger, independent cohort sizes and comprehensive adjustment for intervening factors to paint a clearer picture of the biological aging markers' associations with osteoporosis and provide guidance on their potential clinical relevance in bone health.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155138","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":"PCSK9 in Brain Health and Disease: Liver-Vascular-Brain Interactions in Aging and Disease.","authors":"Mengqi Zhang, Neel S Singhal","doi":"10.14336/AD.2026.0209","DOIUrl":"https://doi.org/10.14336/AD.2026.0209","url":null,"abstract":"<p><p>Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key regulator of peripheral cholesterol metabolism. Inhibitors of hepatic PCSK9 potently reduce low-density lipoprotein cholesterol (LDL-C) and have become a staple of lipid-lowering therapeutic regimens for patients with atherosclerotic cardiovascular disease. Although the role of PCSK9 in the central nervous system (CNS) is less well-defined, accumulating evidence suggests that it modulates CNS cholesterol homeostasis and responses to injury, neuroinflammation, and amyloid-β and tau protein deposition. Thus, peripheral and central PCSK9 molecular actions have important pathophysiological consequences for aging, cerebrovascular disease, and neurodegenerative disease. In this review, we summarize PCSK9 functions in the context of the liver-vascular-brain axis and examine mechanistic and therapeutic links in PCSK9 biology and neurological diseases. By integrating insights from preclinical and clinical research, we highlight the current state of knowledge regarding the potential relevance of PCSK9-inhibiting therapies in brain health and disease. Given the remarkable lipid-lowering effects of PCSK9 inhibitors, advancing our understanding of the multi-organ interactions influenced by PCSK9 may inform future therapeutic strategies, although clinical evidence supporting neurological benefit currently remains limited.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148154873","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":"Astrocytic Ferroptosis: An Integrative Hub Linking Metabolic Dyshomeostasis, Glial Crosstalk, and Neurodegeneration in Alzheimer's Disease.","authors":"Zhimin Lu, Chang Meng, Xiaoyan Ren, Shuo Zhang, Xinqing Xu, Shaofei Hao, Qinglu Wang, Daoqing Zhou","doi":"10.14336/AD.2026.0328","DOIUrl":"https://doi.org/10.14336/AD.2026.0328","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a widespread age-related neurodegenerative disorder. Current therapies targeting Aβ plaques and hyperphosphorylated Tau show limited efficacy. The core pathology of AD involves neuroglial metabolic network collapse, which is tightly associated with brain iron dyshomeostasis and abnormal ferroptosis. As the main iron storage and antioxidant cells in the CNS, astrocytes transform into disease-associated astrocytes under AD conditions. Metabolic reprogramming switches them from a neuroprotective to a pro-ferroptotic phenotype, contributing to thereby exacerbating systemic metabolic dyshomeostasis. This review systematically elaborates the regulatory mechanisms of astrocytic ferroptosis in AD: disordered iron metabolism (e.g., aberrant DMT1/FPN1 expression) induces iron accumulation as the initiation prerequisite; excessive oxidative stress (Ang II/HIF-1α-NOX4 axis-mediated ROS generation) and impaired antioxidant defense (Nrf2-SLC7A11/GPX4 inactivation, ApoE4 dysfunction) serve as core regulatory modules; FTH1 and SAT1 dysregulation elevates the labile iron pool, while AQP4 dysfunction impairs metabolite clearance, amplifying ferroptosis. Moreover, aberrant crosstalk among astrocytes, microglia and oligodendrocytes exacerbates AD-related neurodegeneration. Collectively, astrocytic ferroptosis acts as a key integrative mechanism linking iron dysmetabolism, oxidative stress, neuroinflammation and Aβ/Tau pathology, offering a potential new avenue for decoding AD pathogenesis. Targeting astrocytic ferroptosis is expected to overcome the long-standing therapeutic limitations of conventional AD treatments, providing theoretical support and new directions for developing disease-modifying AD therapies. While individual components including disease-associated astrocytes, brain iron dyshomeostasis, NOX4- and NRF2-related ferroptosis have been documented separately, this review represents the first comprehensive synthesis that identifies astrocytic ferroptosis as a central hub that unifies these fragmented mechanisms into a cohesive pathogenic cascade driving AD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148155157","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}