Ageing research reviews最新文献

{"title":"Aging, Regeneration, and Peripheral Nerve Repair: Integrated Multi-Omics Biomarkers and AI-Enabled Therapeutic Discovery Approaches.","authors":"Muhanad Musaad Alhujaily, Amal Adnan Ashour, Alaa Shafie, Farah Anjum, Tooba Naz Shamsi, Taj Mohammad","doi":"10.1016/j.arr.2026.103424","DOIUrl":"https://doi.org/10.1016/j.arr.2026.103424","url":null,"abstract":"<p><p>Peripheral nerve injury (PNI) remains a major cause of long-term sensory and motor dysfunction, imposing a substantial clinical and socioeconomic burden worldwide. Although peripheral nerves possess intrinsic regenerative capacity, functional recovery is often incomplete because of the complex interplay among axonal degeneration, Schwann cell plasticity, neuroimmune responses, extracellular matrix remodeling, metabolic reprogramming, remyelination, and target reinnervation. Recent advances in transcriptomics, proteomics, epigenomics, metabolomics, and single-cell technologies have expanded molecular characterization of nerve degeneration and regeneration, revealing numerous candidate biomarkers and therapeutic targets. However, biological heterogeneity, fragmented datasets, and the lack of robust predictive frameworks still limit translation into clinical practice. In this review, we provide a comprehensive overview of the cellular and molecular mechanisms governing peripheral nerve repair and examine emerging biomarker classes associated with regenerative competence, neuroinflammation, remyelination, and functional recovery. We also discuss therapeutic strategies targeting Schwann cell reprogramming, axonal growth, immune modulation, metabolic adaptation, and remodeling of the regenerative microenvironment. We further examine how artificial intelligence (AI) and machine learning (ML) may support multi-omics integration, biomarker prioritization, outcome prediction, and therapeutic target discovery, while emphasizing that PNI-specific clinical validation remains limited. We propose a systems-level framework that links molecular signatures with clinical outcomes and highlights the potential of AI-enabled multimodal analytics to support translational research. Age-related molecular variation should be incorporated as an additional analytical dimension, allowing comparison of regenerative and non-regenerative signatures across younger and older tissues. Together, these approaches provide a framework for testing age-aware molecular markers and computational models in future translational studies.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103424"},"PeriodicalIF":12.4,"publicationDate":"2026-10-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149225315","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pain Management Strategies for Older Adults in Palliative Care: A Scoping Review.","authors":"Mélanie Bérubé, Sandrine Linsotan, Lynn Gauthier, Bradley Godwin, Étienne Belzile, Félix Pageau, Thomas Hadjistavropoulos, Michael Verret, Laurence Bourque, Giada Giorgini, Axel Benhamed, Esther van Lieshout, Emil Schemitsch, Line Guénette, Diane Tapp, Steven Papp, Natasha Galant, Éric Troncy, Imane Labzagui, Chantal Morency, Norbert Dion, Guillaume Léonard, Stéphane Pelet","doi":"10.1016/j.arr.2026.103423","DOIUrl":"https://doi.org/10.1016/j.arr.2026.103423","url":null,"abstract":"<p><strong>Background: </strong>With the aging population, the demand for palliative care is expected to increase. Pain management is a critical component of palliative care with unique considerations for older patients. The aim of this scoping review was to map the nature and extent of the evidence on pain management strategies in this population.</p><p><strong>Methods: </strong>We searched databases for peer-reviewed studies and grey literature on pain management in older adults receiving palliative care. Strategies were classified as opioid analgesics, non-opioid medications, procedural, non-pharmacological, educational, and multifaceted interventions. Frequencies and proportions were used to describe the strategies, reported improvements, and levels of evidence.</p><p><strong>Results: </strong>We included 117 studies. Most focused on cancer populations (82/117, 71%), and the majority of participants (98/114, 86%) were aged 65-74 years on average. Overall, 68% of the studies yielded moderate to low level of evidence. Opioids and multifaceted interventions were the most frequently evaluated strategies, each examined in 32% (37/117) of studies. Across both high- and moderate/low-evidence studies, pain reduction was most consistently reported for procedural interventions (3/3, 100%; 3/3, 100%), opioids (3/5, 60%; 25/32, 78%), and multifaceted interventions (4/9, 44%; 20/23, 87%). Favourable findings were most often reported for combinations of opioids, opioids for breakthrough pain, nerve blocks or local anesthesia, cannabis, music or massage therapy, exercise, and biopsychosocial or care organization interventions.</p><p><strong>Conclusion: </strong>This review mapped pain management strategies for older adults in palliative care, identified key evidence gaps, particularly among oldest-old individuals and those with non-cancer conditions, and highlighted the need for stronger research.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103423"},"PeriodicalIF":12.4,"publicationDate":"2026-10-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149221256","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tissue coordination in ageing and disease.","authors":"Kez Cleal","doi":"10.1016/j.arr.2026.103422","DOIUrl":"10.1016/j.arr.2026.103422","url":null,"abstract":"<p><p>How cellular and microenvironmental changes are translated into tissue-level decline remains incompletely understood. Here, we view tissue maintenance through the lens of multicellular coordination, defined as the endogenous management of dependencies among component activities. These dependencies are embodied in a tissue's relational state across signalling networks, epigenetic states, cell composition, and extracellular matrix. The different turnover timescales of these substrates may permit system memory and path dependence. We analyse two constraints that may limit coordination and distributed maintenance: self-reference, wherein the maintenance machinery is itself vulnerable to decline, and a sensing bottleneck, which limits the extent to which cells can perceive and represent age-related change. We explore how tissue architecture and renewal shape the consequences of these constraints for coordination, relational state and tissue function. In some cases, coordination may stabilise a pathological state even after removal of the initiating driver, creating a coordination trap. This view may help explain why tissues exhibit different age-related trajectories and suggests that interventions may also need to restore functional tissue coordination.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103422"},"PeriodicalIF":12.4,"publicationDate":"2026-10-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149217588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The FOXO-aging axis: Epigenetic insights and chromatin mechanisms.","authors":"Tongfeng Fang, Ruihan Ke, Hongyu Ming, Siqi Ye, Dan He, Tao Chen, Yingying Wu","doi":"10.1016/j.arr.2026.103421","DOIUrl":"10.1016/j.arr.2026.103421","url":null,"abstract":"<p><p>Aging is frequently accompanied by profound alterations in the chromatin landscape, leading to widespread changes in transcriptional programs and cellular functions. Forkhead box O (FOXO) proteins, traditionally viewed as downstream effectors of insulin and stress-response signaling, are now emerging as dynamic chromatin regulators that integrate metabolic cues with epigenetic remodeling during aging. In this review, we first outline the major epigenetic and chromatin alterations associated with aging and then examine the emerging role of FOXO proteins as chromatin regulators in this context. We discuss evidence for FOXO pioneer activity and the structural features that facilitate chromatin engagement, followed by FOXO-mediated regulation through ATP-dependent chromatin remodeling and histone modifications, and consider how these mechanisms may shape age-associated chromatin states and cellular senescence. Finally, we discuss the current FOXO-targeting therapeutic strategies and the challenges of achieving isoform- and chromatin context-specific FOXO modulation. Collectively, this review provides a chromatin-centered perspective on the FOXO-aging axis and offers a conceptual framework for future translational and therapeutic studies.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103421"},"PeriodicalIF":12.4,"publicationDate":"2026-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149208285","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multikingdom Gut Microbiome and Immune Aging: A Host-Microbial Signaling Perspective.","authors":"Bowen Jiang, Tianhao Liu, Wenhui Duan, Yuzheng Xue","doi":"10.1016/j.arr.2026.103414","DOIUrl":"https://doi.org/10.1016/j.arr.2026.103414","url":null,"abstract":"<p><p>Immune aging comprises heterogeneous changes in hematopoietic output, immune-cell function, inflammatory regulation, and tissue-specific immune states. In parallel, the gut microbiome undergoes ecological and functional remodeling across the bacteriome, mycobiome, virome, and archaeome, but these changes do not define a single \"aged microbiome\" and vary with host health, frailty, diet, medication exposure, and environmental context. Here, we examine how multikingdom gut microbiome remodeling intersects with distinct trajectories of immune aging. Rather than treating dysbiosis as a uniform upstream cause of immunosenescence, we organize the evidence around four interconnected processes: microbial signal generation, tissue access and compartmentalization, host sensing, and cell-specific interpretation. Age-associated changes in microbial metabolites and immunostimulatory products can influence epithelial barrier function, inflammatory signaling, immunometabolism, hematopoiesis, and lymphoid and myeloid cell states, but evidence strength varies substantially across pathways and microbial kingdoms. Causal support is most developed for selected bacteriome-associated mechanisms in experimental models, whereas aging-specific mechanistic evidence for the mycobiome, virome, and archaeome remains comparatively limited. Importantly, this relationship is reciprocal, because intrinsic immune and tissue aging can also reshape microbial ecology and functional capacity. We therefore view the gut microbiome as a dynamic and potentially modifiable component of immune aging rather than an autonomous driver of immunosenescence. This perspective shifts the translational focus from restoring a youthful microbiome toward targeting microbiome-associated functions and host-response pathways linked to specific immune-aging phenotypes.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103414"},"PeriodicalIF":12.4,"publicationDate":"2026-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186615","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chrononutrition in the aging era: Circadian regulation of metabolism, resilience, and healthy longevity.","authors":"Nadia Granero, Francesca Mancinetti, Patrizia Mecocci, Virginia Boccardi","doi":"10.1016/j.arr.2026.103416","DOIUrl":"https://doi.org/10.1016/j.arr.2026.103416","url":null,"abstract":"<p><p>The increasing prevalence of obesity, type 2 diabetes, cardiovascular disease, and age-related disorders has been linked to a growing mismatch between modern lifestyles and the biological rhythms that regulate human physiology. Chrononutrition, which explores the interaction between meal timing, circadian rhythms, and metabolism, has emerged as a promising strategy to improve metabolic health and support healthy aging. This review examines the molecular and physiological foundations of chrononutrition, focusing on the interplay between central and peripheral circadian clocks, metabolic regulation, and aging processes. We discuss the role of environmental and behavioural zeitgebers, including light exposure, feeding schedules, sleep, and physical activity, in maintaining circadian alignment and metabolic homeostasis. Attention is given to Time-Restricted Eating (TRE) and related meal-timing interventions. Current evidence indicates that aligning food intake with endogenous circadian rhythms improves insulin sensitivity, metabolic flexibility, lipid metabolism, blood pressure regulation, and inflammatory balance, often independently of weight loss. Mechanistically, chrononutrition may also modulate key biological processes associated with aging, including mitochondrial function, autophagy, nutrient sensing, oxidative stress, and inflammaging. By restoring temporal organization across physiological systems, chrononutrition may enhance metabolic resilience and contribute to healthspan extension. Future studies should clarify its long-term effects on biological aging, resilience, and healthy longevity, while defining personalized interventions based on circadian phenotypes.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"103416"},"PeriodicalIF":12.4,"publicationDate":"2026-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149186578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lactylation and methylation: Dual epigenetic codes and potential therapeutic targets in myocardial aging.","authors":"Qian-Qian Niu, Yu-Ting Xi, Ya-Qi Guo, Zheng-Ji Piao, Chun-Rui Zhang, Tian-Yao Li, Dan-Jie Li, Peng Li, Ya-Ling Yin, Vuanghao Lim, Nik Nur Syazni Nik Mohamed Kamal","doi":"10.1016/j.arr.2025.102849","DOIUrl":"10.1016/j.arr.2025.102849","url":null,"abstract":"<p><p>Combating aging has become a central challenge in the life sciences, and myocardial aging, as a fundamental pathological process underlying the development and progression of various cardiovascular diseases, has become a key area in anti-aging research. In recent years, lactylation and methylation, two metabolism-dependent epigenetic modifications, have garnered increasing attention in the context of myocardial aging. Lactylation, mediated by lactate accumulation due to metabolic dysregulation, modifies lysine residues on both histone and non-histone proteins, thereby participating in the regulation of gene transcription, metabolic homeostasis, and inflammatory responses. In parallel, methylation affects gene expression, metabolic remodeling, and mitochondrial function through DNA, RNA, and histone modifications. This review systematically summarizes the regulatory mechanisms of lactylation and methylation in myocardial aging, with a particular focus on their interplay in histone and non-histone protein modification, metabolic regulation, and signaling pathway integration. Furthermore, we evaluate the potential of these reversible modifications as early epigenetic biomarkers and discuss multilayered intervention strategies targeting both lactylation and methylation. Such strategies highlight their translational potential in delaying myocardial aging and mitigating cardiovascular disease. Precisely modulating lactylation and methylation may offer novel theoretical frameworks and therapeutic targets for the prevention and treatment of myocardial aging.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"102849"},"PeriodicalIF":12.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144765808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of antidiabetic medications on the relationship between type 2 diabetes mellitus and cognitive impairment.","authors":"Annalisa Cozza, Chiara Chinigò, Elvira Filicetti, Giada Ida Greco, Rosamaria Lappano, Cinzia Marinaro, Lucia Muglia, Luca Soraci, Andrea Corsonello, Fabrizia Lattanzio, Mara Volpentesta","doi":"10.1016/j.arr.2025.102834","DOIUrl":"10.1016/j.arr.2025.102834","url":null,"abstract":"<p><p>Type 2 diabetes mellitus (T2DM)-related cognitive impairment (CI) has garnered increasing attention in recent research and is emerging as a highly relevant area of study. T2DM is a chronic and globally prevalent condition characterized by insulin resistance, hyperglycemia, oxidative stress, neuroinflammation, and cerebrovascular dysfunction, factors that collectively contribute to cognitive decline. Notably, T2DM is strongly associated with neurodegenerative conditions, ranging from mild cognitive impairment (MCI) to dementia. This review explores the potential neuroprotective effects of various antidiabetic drugs, including insulin-sensitizing agents (metformin and pioglitazone), sodium-glucose co-transporter 2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1 RAs), and dipeptidyl peptidase-4 inhibitors (DPP-4is). These medications exert their effects through multiple mechanisms, such as reducing neuroinflammation and oxidative stress, decreasing Aβ accumulation and apoptosis, enhancing cerebral glucose metabolism, and promoting neuroplasticity, processes directly implicated in the interplay between T2DM and cognitive decline. The review highlights the therapeutic potential of these agents in mitigating CI and supporting brain health in individuals with T2DM. However, given the conflicting nature of current clinical evidence, further research is needed to clarify their cognitive benefits, elucidate underlying mechanisms of action, and assess their long-term effects on cognitive outcomes in this population.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"102834"},"PeriodicalIF":12.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144638819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Telomerase dynamics in stem cells: Unraveling the molecular nexus of cellular aging and regeneration.","authors":"Yanhua Jiang, Yongjian Zhou, Yutao Wang, Zhe Li, Ghulam Md Ashraf, Liang Guo","doi":"10.1016/j.arr.2025.102853","DOIUrl":"10.1016/j.arr.2025.102853","url":null,"abstract":"<p><p>The expression levels of telomerase exhibit regulatory heterogeneity across different cell types and various biological stages of cell development. The expression of telomerase is dynamically regulated across cell types and developmental stages, with its activity predominantly determined by the abundance of its catalytic subunit, telomerase reverse transcriptase (TERT). Telomerase levels are typically high in the pluripotent embryonic stem cells, germline cells, and cancer cells, and silenced in the terminally differentiated cells. Minimal telomerase activity is present in the stem and progenitor cells of highly proliferative tissues, although preventing telomere shortening is beyond common sense in the field of biology and cannot be achieved, eventually leading to replicative senescence. While telomerase silencing in somatic cells and adult stem cells acts as a barrier to tumorigenesis by limiting their lifespan, the eventual exhaustion of stem cell pools leads to tissue dysfunction and aging. Telomerase reactivation via telomerase overexpression represents a potential strategy to reverse stem cell aging and rejuvenate aged or dysfunctional tissues. In this review, we discuss the dynamics of telomere (length, activity, and expression level) in pluripotent and adult stem cells as well as their impact on aging. Notably, we have summarized the recent evidence in the application of mesenchymal stem cells immortalized through exogenous telomerase expression in regenerative medicine.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"102853"},"PeriodicalIF":12.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144786097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Strategies to rescue mitochondria in Parkinson's disease: The significance of mitochondrial transfer.","authors":"Junhan Liang, Zhaoqin Su, Gongmeiyue Su, Madiha Rasheed, Shiyi Tang, Hafsa Sunniya, Mohamed Maazouzi, Yaoyuan Cui, Junxiao Wang, Xuezhe Wang, Jing Yang, Mingchao Ding, Zhao Li, Yulin Deng","doi":"10.1016/j.arr.2025.102856","DOIUrl":"10.1016/j.arr.2025.102856","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a common neurodegenerative disorder characterized by dopaminergic neuronal degeneration and pathological α-synuclein accumulation. Mitochondrial dysfunction is a central feature in PD pathogenesis, contributing to impaired bioenergetics, oxidative stress, neuroinflammation, and defective organelle communication. This review synthesizes the current understanding of mitochondrial quality control mechanisms, including fission, fusion, mitophagy, and biogenesis, and their disruption in PD. Particular emphasis is placed on the role of intercellular mitochondrial transfer as a compensatory mechanism. Emerging evidence suggests that mitochondria can be transferred between neurons and glial cells through tunneling nanotubes, extracellular vesicles, and gap junctions, offering protective effects by restoring metabolic function and attenuating cellular stress. We examine the molecular mediators of these transfer pathways, the influence of PD-associated mutations, and the bidirectional dynamics between donor and recipient cells. Additionally, we explore translational strategies, including mitochondrial transplantation, bioengineered mitochondria, and stem cell-based delivery systems. While preclinical models demonstrate promising therapeutic outcomes, clinical translation faces challenges, including targeting specificity, mitochondrial viability, and immune compatibility. By integrating mechanistic insights with therapeutic developments, this review highlights mitochondrial transfer as a novel and promising approach in the future treatment of PD, potentially addressing longstanding limitations in conventional neuroprotective strategies.</p>","PeriodicalId":93862,"journal":{"name":"Ageing research reviews","volume":" ","pages":"102856"},"PeriodicalIF":12.4,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144801212","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}