Aging and Disease最新文献

{"title":"The Clinical Relevance of FTO as a Demethylase Beyond Cancer: Molecular Mechanisms and Therapeutic Opportunities.","authors":"Cun-Yang Guo, Yi-Fei Du, Hui-Cong Yan, Xin-Ming Fan, Fang-Qi Tian, Ping Xu","doi":"10.14336/AD.2025.0916","DOIUrl":"https://doi.org/10.14336/AD.2025.0916","url":null,"abstract":"<p><p>The fat mass and obesity-associated (FTO) gene is a key gene that has been linked to obesity and metabolic regulation. FTO single nucleotide polymorphisms (SNPs) significantly contribute to the pathophysiology of various multisystem diseases via epigenetic mechanisms. Although FTO has been extensively reviewed in the context of cancer, a comprehensive evaluation of its role in non-malignant diseases is currently lacking. This review aimed to systematically assess the molecular functions of FTO in the context of diseases other than cancer based on recent insights from the literature. Relevant studies were retrieved by systematically searching the PubMed database to explore the mechanisms through which FTO acts as a mediator of demethylation, its biological activities, and its functional roles in a spectrum of non-oncologic diseases. To explore pharmacological interactions, AutoDockTools 1.5.7 was used to simulate binding interactions between FTO and conventional therapeutic agents. Additionally, we conducted a bibliometric analysis using VOSviewer to visualize the frequency and co-occurrence of FTO-related terms, thereby helping to map research trends and knowledge gaps in the field. FTO regulates gene expression by modulating RNA methylation, particularly through the demethylation of N6-methyladenosine (m⁶A), thereby influencing RNA splicing, stability, and translation. This regulatory activity plays a major role in processes such as inflammation and fibrosis. Dysregulation of FTO has been implicated in several non-malignant diseases, including metabolic disorders, neurological diseases, and cardiovascular conditions. Computational docking studies showed that FTO exhibited strong binding affinity with two drugs and moderate affinity with eight others. Bibliometric analysis revealed high-frequency keywords and visualized research hotspots pertaining to FTO, providing valuable insight into current areas of scientific interest and potential future directions of study. FTO functions as a key epigenetic regulator in non-cancerous diseases and represents a promising biomarker and therapeutic target. Our findings underscore the importance of FTO-drug interactions and suggest that small-molecule FTO modulators may hold therapeutic value for managing a variety of non-oncologic conditions.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074363","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 the Milieu in Neurodegenerative Disease: Time for \"Imprecision Medicine\"?","authors":"Joseph F Quinn","doi":"10.14336/AD.2025.0966","DOIUrl":"https://doi.org/10.14336/AD.2025.0966","url":null,"abstract":"<p><p>The possibility of developing precision therapies for neurodegenerative disease is tantalizing, and efforts are under way with several diseases, including Alzheimer's, Parkinson's and Huntington's disease. Despite strong basic neuroscience foundations and excellent clinical trial design, however, these efforts have been disappointing. We present an argument for a complementary approach of targeting the brain milieu in order to achieve disease-modifying effects in patients with or at risk of neurodegenerative disease. We suggest that a milieu-directed \"brain health\" approach can be applied across a range of at-risk individuals in a specific, quantitative, evidence-based manner. In support of this position, we present data from epidemiologic studies and clinical trials. We propose a program of rigorous research to validate and implement this complement to precision medicine which skeptics might call \"imprecision medicine.\"</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074367","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":"Linking Individual Variability of Multi-modal Connectivity, Lifestyle, Psycho-Social Factors and Cognition in Older Adults.","authors":"Mingxian Zhang, Susanne Moebus, Nico Dragano, Nora Bittner, Svenja Caspers","doi":"10.14336/AD.2025.0428","DOIUrl":"https://doi.org/10.14336/AD.2025.0428","url":null,"abstract":"<p><p>Older adults exhibit greater heterogeneity than younger adults in behavior, cognition, and brain, which may be influenced by a range of factors, including lifestyle. While previous studies have assessed brain heterogeneity by evaluating the dissimilarity of individual brain connectivity, further empirical evidence is needed to understand the factors behind brain heterogeneity in older adults. Using data from the 1000BRAINS study (N = 461, aged 55-85 years), we analyzed the individual variability (IV) of the functional (IVFC) and structural (IVSC) connectivity across 421 brain regions. We aimed to explore the relationship between network-wise and region-wise brain connectivity IV (i.e., both IVFC and IVSC), lifestyle, including psycho-social factors (e.g., self-reported smoking, physical activity, alcohol consumption, and social integration), and cognitive function via partial least squares correlation, stratifying analyses by age subgroups (55-64, 65-74, and ≥ 75 years), separately. Our results showed that higher connectivity IV was linked to lower social integration and/or higher smoking, and lower cognitive performance (e.g., episodic memory and executive control). For the network-wise analysis, we observed contributions from both IVFC and IVSC across eight networks, especially IVSC in the salience and ventral attention networks. Region-wise, significant contributions came primarily from the connectivity IV of specific brain regions (e.g., inferior frontal gyrus, right anterior cingulate cortex). This result pattern varied by age group. Connectivity IV was positively correlated with smoking in the age 65-74 group and negatively correlated with alcohol consumption in the age ≥ 75 years group. Overall, IVSC contributed more than IVFC with age. These findings suggest that unhealthy lifestyle and social isolation might be associated with differences in neural resources, which may be linked to increased individual brain heterogeneity and, in turn, to lower cognitive performance in older adults, supporting the revised Scaffolding Theory of Aging and Cognition (STAC-r).</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074284","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":"Association between Visual, Hearing and Dual Sensory Impairment and the Frailty Syndrome.","authors":"Humberto Yévenes-Briones, Francisco Félix Caballero, Aitana Vázquez-Fernández, Pablo Martinez-Amezcua, Teresa T Fung, Esther Lopez-Garcia","doi":"10.14336/AD.2025.0342","DOIUrl":"https://doi.org/10.14336/AD.2025.0342","url":null,"abstract":"<p><p>Sensory loss has been associated with multiple adverse health conditions. However, the combined effect of visual and hearing impairment on frailty is unknown. The aim of this study was to examine the association between visual, hearing, and dual-sensory impairment and frailty prevalence. This cross-sectional study investigated 105,406 participants aged ≥39 years from the UK Biobank study. Visual acuity was measured with a chart, as the logarithm of the minimum angle of resolution (LogMAR); functional auditory capacity was measured with a digit triplet test, as the speech reception threshold in noise (SRTn). Dual sensory impairment was defined as the presence of both visual impairment (LogMAR &;gt 0.3 units) and hearing impairment (SRTn ≥ -5.5 dB SNR). To define the frailty syndrome, two methods were used, the frailty phenotype and the FRAIL scale. Analyses were conducted using logistic models adjusted for relevant confounders. Among the participants, 54.3% were women, with a mean age of 56.8 years (SD: 8.1, range 39 to 72). The prevalence of frailty was 3.5%, defined with the frailty phenotype, and 3.6%, using the FRAIL scale. For visual impairment, the OR (95% CI) of frailty was 1.51 (1.28-1.79) for the frailty phenotype, and 1.31 (1.10-1.57), for the FRAIL scale. For hearing impairment, in comparison with having normal hearing, the OR (95% CI) associated with insufficient and poor hearing were 1.32 (1.20-1.45) and 1.83 (1.53-2.19), respectively for the frailty phenotype, and 1.32 (1.19-1.46) and 1.93 (1.60-2.33) for the FRAIL scale. Estimates for the association between dual-sensory impairment and frailty were 2.22 (1.65-2.99) for the frailty phenotype, and 1.73 (1.23-2.42) for the FRAIL scale. Visual and hearing impairments were related to frailty. Having dual-sensory impairment was associated with twice the likelihood of frailty syndrome in comparison with having none of them.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074346","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 Dual Decline to Clinical Consequences: Mechanistic Pathways and Health Outcomes of Motoric Cognitive Risk Syndrome.","authors":"Yiwei Zhao, Tao Wei, Bo Zhao, Yuanyuan Chen, Zhibin Wang, Yi Tang","doi":"10.14336/AD.2025.0730","DOIUrl":"https://doi.org/10.14336/AD.2025.0730","url":null,"abstract":"<p><p>Motoric cognitive risk (MCR) syndrome, defined by the coexistence of slow gait and subjective cognitive decline (SCD), is increasingly recognized as an intermediate stage between normal aging and overt cognitive impairment. Its prevalence varies across populations, largely shaped by demographic, socioeconomic, and lifestyle factors. Neuroimaging evidence further supports this construct, demonstrating gray matter atrophy in prefrontal and premotor regions alongside white matter hyperintensities, both of which have been linked to motor and cognitive deficits in individuals with MCR. The pathogenesis of MCR is likely multifactorial, involving metabolic, inflammatory, and genetic mechanisms that interact to accelerate vulnerability to neurodegeneration. Importantly, MCR has been shown to predict adverse outcomes, including dementia, falls, frailty, and increased mortality, underscoring its potential utility as an early clinical marker of neurodegenerative progression. Given these implications, recent studies have explored preventive and therapeutic strategies, such as aerobic exercise, dual-task cognitive training, dietary interventions, and pharmacological approaches targeting inflammation and metabolic dysfunction, that may mitigate MCR-related risks. Future research should aim to refine diagnostic criteria, integrate multimodal assessments, and develop personalized interventions to more effectively prevent or delay cognitive and motor decline in aging populations.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074359","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":"Lactylation Modification and Aging: A Molecular Link in the Life Process.","authors":"Min Shi, Honyu Li, Haiyan Lin, Qiang Tang","doi":"10.14336/AD.2025.0509","DOIUrl":"https://doi.org/10.14336/AD.2025.0509","url":null,"abstract":"<p><p>In recent years, significant progress has been made in the research of aging and aging-related diseases. Epigenetic alterations, as an important marker of aging, are also one of the mechanisms that trigger aging. Lactylation modification, also known as lactylation, is a post-translational modification form (PTM) that uses lactate and lysine residues as substrates and belongs to an important field of epigenetic alterations. As an emerging research hotspot in recent years, it has made considerable breakthroughs in the study of human-related diseases, especially cancer. During the aging process, lactylation modification occurs in the body due to changes in lactate concentration, thereby affecting other aging mechanisms. This article reviews lactylation modification and cellular senescence, mitochondrial dysfunction, autophagy and energy metabolism, summarizes the current influence of lactylation modification on aging-related mechanisms, and makes bold predictions for future research based on the existing research differences.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074352","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":"Gut Virome and Aging: Phage-Driven Microbial Stability and Immune Modulation.","authors":"Kaleem Ullah, Rabia Kanwar, Saqib Ali, Saif Uddin, Izza Izza, Irfan Ahmad, Khalid J Alzahrani, Abdul Qadeer, Chun-Ting Chu, Chien-Chin Chen","doi":"10.14336/AD.2025.0854","DOIUrl":"https://doi.org/10.14336/AD.2025.0854","url":null,"abstract":"<p><p>The gut harbors trillions of microbes that play essential roles in metabolism and immunological functions. The virome, an important but understudied component of the gut microbiota, comprises bacteriophages commonly referred to as bacterial viruses, among other inhabitants. Understanding the interplay between the gut virome and bacteria can illuminate the dynamics of microorganisms in both healthy and diseased states. This knowledge can open new avenues for treatment, such as phage therapy and microbiota modulation, which aim to restore balance in the gut and improve overall health. The composition and diversity of the gut microbiome and virome undergo significant changes, which have been linked to increased susceptibility to infections, chronic inflammation, and age-related disease. Exploring the gut virome's role in aging may provide insights into how viral and bacterial interactions influence immune senescence and gut resilience in the elderly population. This review provides an overview of the current understanding of the relationship between the gut virome, specifically phages associated with gut bacteria, and mechanisms of phage-host interactions, shedding light on how these factors affect and influence communities. Additionally, this review also explores the impact of the gut virome on gut resilience and its role in shaping and influencing the host's immune response. Maintaining a healthy gut requires a stable and robust virome. Therefore, future research on the virome is crucial for the development of microbe-based products that enhance human and animal health and aid in addressing specific diseases.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145085016","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":"Circulating Cell-free DNA Fragmentomics Detection and Beyond.","authors":"Tianliang Liu, Zhicheng Li, Shifu Chen, Jiasheng Zhong","doi":"10.14336/AD.2025.1029","DOIUrl":"https://doi.org/10.14336/AD.2025.1029","url":null,"abstract":"<p><p>Circulating cell-free DNA (cfDNA) comprises DNA fragments released into bodily fluids via apoptosis, necrosis, or phagocytosis. cfDNA encapsulates both fragmentomics (structural) and non-fragmentomics (sequence/epigenetic) information from source cells, thereby representing a promising biomarker. While non-fragmentomics analyses have enabled diverse diagnostic applications, they often falter in diseases with subtle or widespread genomic changes due to low cfDNA abundance and clonal hematopoiesis interference. Emerging evidence reveals that cfDNA fragmentation is shaped by nucleosome occupancy, nuclease activity, and epigenetic factors, yielding distinct patterns in fragment size, end motifs, nucleosome footprints, and topology. These fragmentomics signatures diverge markedly between healthy and diseased states, and across age group, offering opportunities to complement non-fragmentomics and enhance accuracy. This review delineates key cfDNA fragmentomics targets, elucidates fragmentation mechanisms, and explores clinical applications in the context of diseases and aging. We further survey cutting-edge technologies and computational algorithms and discuss implementation challenges alongside future prospects.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074301","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":"Fever Induces Long-Term Synaptic Enhancement and Protects Learning in an Accelerated Aging Model.","authors":"Fusheng Du, Qi Wan, Oleg O Glebov","doi":"10.14336/AD.2025.0591","DOIUrl":"https://doi.org/10.14336/AD.2025.0591","url":null,"abstract":"<p><p>The physiological impact of fever on the brain remains poorly understood. Here, we demonstrate that temperature increases by yeast injection in rats (N=9) and by whole-body hyperthermia in mice (N=7) triggers structural synaptic enhancement in the prefrontal cortex through a mechanism involving AMPA-type glutamate receptors and protein translation (N=6). Repeated pyrexia induction in juvenile rats (N=9) results in synaptic strengthening that persists into adulthood, mitigating learning deficits and synaptic loss in a D-galactose model of accelerated aging (N=9-11). Our results show how common environmental conditions may shape brain function in the long-term via synaptic plasticity, warranting further exploration of thermal treatment for cognitive protection in aging.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074340","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":"PGC-1α Regulates Exercise Intensity-Dependent Atrial Remodeling and Fibrillation in Rats.","authors":"Jingwen Xiao, Jiancheng Zhang, Yan Zhang, Yu Jiang, Chenqi Yang, Xiaona Lin, Zhengnan Lin","doi":"10.14336/AD.2025.10621","DOIUrl":"https://doi.org/10.14336/AD.2025.10621","url":null,"abstract":"<p><p>Exercise has well-documented cardiovascular benefits, but excessive training has been associated with an increased risk of atrial fibrillation (AF). The molecular mechanisms linking exercise intensity to atrial remodeling and AF susceptibility remain incompletely understood. Here, we investigated the effects of varying treadmill exercise intensities on atrial structure, metabolism, and electrophysiology in rats. AF inducibility was assessed using burst pacing, and atrial dimensions were evaluated by echocardiography. Histology was performed to quantify fibrosis and lipid accumulation. Metabolic and signaling pathways were examined through biochemical assays and Western blotting. We found that exercise intensity exhibited a nonlinear, J-shaped relationship with AF susceptibility. Moderate training (B-Mod) resulted in the lowest AF incidence and duration, whereas high-intensity training (B-Int) produced frequent and sustained episodes. Echocardiography revealed atrial enlargement in sedentary (B-Sed) and B-Int groups but preserved dimensions in B-Mod. Histological analysis showed marked fibrosis in B-Int but only minimal changes in B-Mod, along with progressive lipid deposition and impaired glucose handling at higher intensities. Importantly, PGC-1α expression paralleled AF susceptibility, peaking at moderate intensity, and was associated with decreased TGF-β and enhanced MAPK signaling. Pharmacological inhibition of PGC-1α with SR-18292 abolished these protective adaptations, increased fibrosis, disrupted glucose-lipid balance, and eliminated the correlation between Kv1.5 expression and AF resistance. In summary, moderate-intensity exercise protects against AF by optimizing atrial remodeling, metabolism, and electrophysiology through PGC-1α-dependent pathways. Both insufficient and excessive training impair these adaptations, increasing AF susceptibility. These findings identify PGC-1α as a central regulator of atrial health and a potential therapeutic target for AF prevention.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145074369","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}