Ageing Research Reviews最新文献

{"title":"Exercise and the hallmarks of cardiovascular aging","authors":"Dan Zhong ,&nbsp;Benjamin Fernández-García ,&nbsp;Priyanka Gokulnath ,&nbsp;Kexin Lin ,&nbsp;Guoping Li ,&nbsp;Guido Kroemer ,&nbsp;Carlos López-Otín ,&nbsp;Junjie Xiao","doi":"10.1016/j.arr.2026.103030","DOIUrl":"10.1016/j.arr.2026.103030","url":null,"abstract":"<div><div>Cardiovascular diseases (CVDs), including hypertension, heart failure, atherosclerosis and myocardial infarction, remain the leading cause of morbidity and mortality worldwide. Aging is a predominant risk factor for CVD. Cardiovascular aging is characterized by progressive structural changes at the cellular level and functional decline within the cardiovascular system, ultimately contributing to the onset and progression of CVD. These changes include alterations in left ventricular (LV) systolic and diastolic function, an increased incidence of sinus node dysfunction, myocardial hypertrophy, arterial stiffness, and fibrosis. Therefore, understanding the molecular mechanisms underlying cardiovascular aging and identifying interventions that can slow or mitigate its progression holds significant promise for CVD prevention and treatment. Numerous epidemiological and experimental studies have consistently demonstrated that physical activity or exercise training exerts protective effects against cardiovascular aging. However, the molecular mediators and underlying mechanisms of these benefits are not completely understood. Therefore, further investigation is warranted to elucidate these mechanisms, given their potential as novel therapeutic targets. In this review, we comprehensively synthesize molecular, preclinical, clinical, and epidemiological evidence to underscore the positive effects of exercise on cardiovascular aging. This review systematically investigates how exercise modulates the key biological hallmarks of cardiovascular aging, including deterioration of protein homeostasis (proteostasis), genomic instability, epigenetic disturbances, mitochondrial dysfunction, cellular senescence, chronic inflammation, and dysregulated neurohormonal signaling. The mechanistic insights of exercise-induced adaptations presented in this review may provide a valuable foundation for future investigations, paving the design of tailored exercise regimens aimed at mitigating the progression of cardiovascular aging.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103030"},"PeriodicalIF":12.4,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146044331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluating senescence-targeted approaches in Alzheimer’s Disease: What we know and what lies ahead","authors":"Pratik Prashant Doshi ,&nbsp;Sakshee Hemant Desale ,&nbsp;Aarti Ashok Khutale ,&nbsp;Sarvesh Sabarathinam ,&nbsp;Swathi Suresh","doi":"10.1016/j.arr.2026.103029","DOIUrl":"10.1016/j.arr.2026.103029","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) is a progressive and irreversible neurodegenerative disease, which represents the most prevalent dementia worldwide. Although amyloid-β (Aβ) and tau pathology have been the classic focus of treatment, accumulating evidence indicates that ageing-associated cellular senescence plays a central role in AD pathogenesis. Senescent neurons, astrocytes, microglia and endothelial cells accumulate in the ageing and Alzheimer’s brain and adopt a senescence-associated secretory phenotype characterized by sustained release of pro-inflammatory and neurotoxic factors. This chronic inflammatory milieu promotes neurodegeneration, disrupts the synaptic activity and is involved in cognitive deficit. Senolytics, which selectively eliminate senescent cells, have demonstrated benefit in multiple preclinical models of AD, including decreased neuroinflammation, improvement in neuronal function and cognitive performance. Several senolytic agents, such as dasatinib, quercetin, fisetin and navitoclax, hit anti-apoptotic modalities that support the survival of senescent cells. Early-phase human studies suggest the feasibility of senescence-targeted interventions and indicate that senescence-associated molecular changes may compromise blood–brain barrier integrity. Consistently, preclinical studies demonstrate partial restoration of barrier function following senolytic therapy; however, clinical translation remains limited and at an early stage. Major challenges include the identification of senolytic agents with effective central nervous system penetration, the determination of optimal dosing regimens and treatment schedules, generation of robust long-term safety profile in human population, and the development of predictive biomarkers to guide patient selection and clinical study design. As senolytics and senomorphic strategies continue to evolve, they hold promise as complementary approaches to existing anti-amyloid and anti-tau therapies by offering a multi-mechanistic approach toward AD modification. This review synthesizes current evidence on cellular senescence in AD, outlines the mechanistic rationale for senescence-targeted therapies, summarizes available clinical data, while providing future directions for integrating senolytics into AD management.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103029"},"PeriodicalIF":12.4,"publicationDate":"2026-01-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146020914","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Proteolysis-targeting chimera (PROTAC): A promising senolytic strategy","authors":"Gang Fan ,&nbsp;Qingping Zhang ,&nbsp;Weiming Guo ,&nbsp;Miao Liu ,&nbsp;Dong Tan ,&nbsp;Zhihan Tang ,&nbsp;Jing Yang","doi":"10.1016/j.arr.2026.103027","DOIUrl":"10.1016/j.arr.2026.103027","url":null,"abstract":"<div><div>Senescent cells (SCs) accumulate with aging and contribute to the development of age-related pathologies. These cells evade apoptosis through upregulation of senescent cell anti-apoptotic pathways (SCAPs), making their selective elimination, a strategy termed senolysis, a promising therapeutic avenue. Proteolysis-targeting chimeras (PROTACs) represent an emerging class of bifunctional molecules that exploit the ubiquitin-proteasome system to degrade specific target proteins. By concurrently binding to a protein of interest and an E3 ubiquitin ligase, PROTACs catalyze the degradation of SCAP components, offering a novel pharmacological approach to clear SCs. This review summarizes the principles and recent advances in PROTAC technology, with a focus on its application as a senolytic strategy. We highlight how PROTACs can overcome limitations of conventional inhibitors, such as targeting “undruggable” SCAP proteins, and provide a comparative analysis of major PROTAC classes targeting BCL-2 family members, p53, BRD4, SA-β-gal, and other emerging senescence regulators. Furthermore, we also discuss the aging-specific biological and translational challenges, including altered proteasomal activity, pharmacokinetics, tissue microenvironment, and immune clearance, which must be addressed to advance PROTAC senolytics toward clinical use in age-related diseases.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103027"},"PeriodicalIF":12.4,"publicationDate":"2026-01-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146013882","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Decoding synaptic imbalance in neurodegenerative diseases: From pathological analysis to targeted intervention","authors":"Xiong Li ,&nbsp;Rui Wan ,&nbsp;Yang Zhao ,&nbsp;Yumeng Wu,&nbsp;Xuehua Chen,&nbsp;Qianqian Li,&nbsp;Chengliang Luo","doi":"10.1016/j.arr.2026.103028","DOIUrl":"10.1016/j.arr.2026.103028","url":null,"abstract":"<div><div>Synapses serve as the central functional components mediating information transmission, integration, and storage within the central nervous system (CNS). Their functionality depends on the synergistic interplay of the presynaptic membrane, synaptic cleft, and postsynaptic membrane–three structures that collectively sustain neurotransmitter secretion, postsynaptic signaling, and synaptic plasticity. Of note, synaptic impairment represents an early, shared pathological hallmark across aging and age-related neurodegenerative disorders like Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), and Amyotrophic lateral sclerosis (ALS). This damage emerges prior to the demise of neuronal cell bodies and the manifestation of clinical symptoms, with its location and severity directly shaping disease phenotypes. Importantly, such synaptic dysfunction is closely linked to the pathological proteins specific to each disorder. This review comprehensively synthesizes current research advances regarding synaptic impairment in age-related neurodegenerative diseases. It elaborates on the location-specific pathological features of synaptic damage in AD, PD, HD, and ALS, with particular emphasis on their associations with disease-related pathological markers. Additionally, the work unpacks five core mechanisms driving synaptic dysfunction: the toxic effects of pathological proteins, dysregulated synaptic protein homeostasis, excitotoxicity coupled with disrupted calcium balance, oxidative stress and inflammatory responses, and deficiencies in neurotrophic factors. Ultimately, it summarizes potential biomarkers and targeted intervention strategies, aiming to provide a systematic reference for mechanistic investigations, early diagnosis, and clinical management of neurodegenerative diseases.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103028"},"PeriodicalIF":12.4,"publicationDate":"2026-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145999965","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Nanotechnology-based advancements in Parkinson's therapy: Exploring animal models and clinical insights in neurodegenerative disorders","authors":"Dnyandev G. Gadhave ,&nbsp;Varsha V. Kale ,&nbsp;Aishwarya P. Kade ,&nbsp;Onkar R. Jadhav ,&nbsp;Vrashabh V. Sugandhi ,&nbsp;Vishal B. Babar ,&nbsp;Shubham Khot ,&nbsp;Chandrakant R. Kokare ,&nbsp;Keshav Raj Paudel","doi":"10.1016/j.arr.2026.103026","DOIUrl":"10.1016/j.arr.2026.103026","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a chronic neurological disorder characterized by loss of body movement control due to dopamine abnormalities. PD leads to various pathological symptoms, including muscle stiffness, bradykinesia, tremors, and postural disturbances. As a severe disease, PD caused approximately 329,000 deaths worldwide in 2019. However, PD treatment is very challenging; thus, alternative therapeutic strategies are in high demand. The primary therapeutic hurdle in PD therapy is the blood-brain barrier (BBB). This biological barrier further protects against dangerous foreign substances and drugs in the brain, which limits therapeutic action in PD. Currently, there are several approved medications for PD therapy, although the majority only address associated symptoms. Unfortunately, because of related adverse effects, existing treatments have not been able to slow the severity of PD. This illness is initiated and progresses by specific pathogenic mechanisms like α-synuclein aggregation, mitochondrial dysfunction, oxidative stress, and neuroinflammation. As a result, a patient with PD has a limited chance of surviving roughly about 14.5 years. Therefore, to better understand and improve the overall survival rate, it is necessary to understand the different pathogenic processes behind the progress of PD. However, in the current and past decade, nanotechnology has rapidly expanded into the field of treatment and diagnosis of mental illnesses. Therefore, the review underscored recent insights into PD pathogenesis, neuropathogenic mechanisms, advancements in theragnostic and therapeutic strategies, nanotherapeutics, current clinical trial updates, and emerging PD therapeutic development. That has aided scientists in developing alternative approaches to deal with the drawbacks of PD's conventional therapies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103026"},"PeriodicalIF":12.4,"publicationDate":"2026-01-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145979433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The gut microbiota dysbiosis in geriatric multimorbidity: Pharmacotherapeutic implications, pathophysiological mechanisms, and precision modulation strategies","authors":"Duo Yang ,&nbsp;Dan Ren ,&nbsp;Yu Zhang ,&nbsp;Yuanzhu Hao ,&nbsp;Yixing Yue ,&nbsp;Qian Li ,&nbsp;QingLing Fan ,&nbsp;Chao Sun ,&nbsp;Manli Cui ,&nbsp;Mingxin Zhang","doi":"10.1016/j.arr.2026.103023","DOIUrl":"10.1016/j.arr.2026.103023","url":null,"abstract":"<div><div>Aging around the world is accelerating. With that comes the intersection of geriatric multimorbidity and polypharmacy, creating a large uncertainty about the pharmacological efficacy and therapeutic consequences of medications used when multiple concurrent health issues exist. The gut microbiota coordinates the way drugs work through multiple pathways: through the way drugs are metabolised, the way they maintain immune homeostasis, and the way they regulate the epithelial barrier. For these reasons, the gut microbiota is becoming an important therapeutic target for optimizing precision medicine strategies in treating patients with geriatric multimorbidities. In this narrative review, we systematically synthesize the evidence regarding how gut dysbiosis leads to decreased efficacy of multi-drug regimens through the interplay between metabolism, immune response, and barrier function in aging patients with multimorbidities, and we evaluate targeted interventions. Furthermore, we demonstrate that current interventions (e.g., probiotics, prebiotics, fecal microbiota transplants (FMT), phage therapy, and dietary modulation) have unique benefits but are limited by inter-individual variability, safety concerns, and a lack of proven long-term efficacy. Thus, many areas of microbiota-drug interactions in older adults with multimorbidity should be explored through future research. Key areas to address are: the establishment of large, multicenter longitudinal cohorts of older adults with multimorbidity that would allow for repeated collection of microbiota profiles, medication use, and health outcomes to identify the evolving interaction between multimorbidity, microbiota, and polypharmacy; the urgent need for standardized and integrated databases of microbiome-drug interactions that harmonize data formats, provide metabolic annotations and medication identifiers in order to support reproducible cross-study validation; and the further validation and application of artificial intelligence (AI) and machine learning (ML) in clinical trials. High-dimensional data collected from cohorts and databases will enable the development of predictive algorithms to identify individual drug responses and how effective microbiota-targeted interventions will be; these algorithms must then be prospectively validated. Ultimately, these initiatives are necessary to move toward the personalized management of microbiota-drug interactions in older adults with multimorbidity, providing greater safety of polypharmacy and promoting healthy aging.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103023"},"PeriodicalIF":12.4,"publicationDate":"2026-01-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145992313","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Insights into mechanism of ionic liquids for protein stability: Future implications for neurodegeneration treatment","authors":"Kajal Sharma ,&nbsp;Mohammad Shahid ,&nbsp;Rajan Patel ,&nbsp;Asimul Islam","doi":"10.1016/j.arr.2026.103024","DOIUrl":"10.1016/j.arr.2026.103024","url":null,"abstract":"<div><div>Neurodegenerative diseases are characterized by a gradual loss of neurons, cellular dysfunction, loss of intricate synaptic networks and brain damage, which are going to be the second leading cause of death in future. These proteinopathies are marked by abnormal amyloid fibril deposition, aberrant aggregation of misfolded proteins via polymerization, where protein aggregates serve as key pathological hallmarks in Alzheimer’s, Parkinson’s, and multiple system atrophy disorders. These toxic aggregates accumulate in the brain and disrupt neuronal function, targeting motor neurons, spinal cord, and ultimately leading to respiratory failure and death. As population ages, the prevalence of these neuronal disorders rises significantly, emphasizing to approach effective treatment for risk reduction. In the pursuit of developing effective anti-amyloidogenesis therapeutic agents, ionic liquids (ILs) continue to receive the least attention. ILs have emerged as promising substitute for conventional solvents, owing to their unique physicochemical properties that facilitate protein refolding, mitigate denaturation, amyloidogenesis, and prevent aggregation. This review critically addresses intricate IL-protein interactions, dictated by anions-cations composition of ILs, their polarity, hydrophobicity, kosmotropicity, chaotropicity, amphiphillicity, and network, which modulate protein behavior and support structural and functional integrity. This article also underscores the need for precision in IL selection, ensuring their properties align with the desired structural outcome. We showcase ILs as a promising therapeutic avenue for neurodegenerative diseases, demonstrating their potential to modulate pathological protein aggregation and enhance protein homeostasis. Lastly, this review of outstanding research works, account for current lacunae that will guide future perspectives for the rational designing of IL for protein stabilization and offers new strategies for addressing underlying mechanism of ageing disorders.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"117 ","pages":"Article 103024"},"PeriodicalIF":12.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949429","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sepsis-induced cardiomyopathy: A comprehensive review of pathogenic mechanism and therapeutic strategies","authors":"Zhang Shangzu ,&nbsp;Li Qiyang ,&nbsp;Peng Zhiyun ,&nbsp;Shan Yunan ,&nbsp;Liu Xinbang ,&nbsp;Chen Yan ,&nbsp;Zeng Zhaoshang ,&nbsp;Tang Zhongxiang ,&nbsp;Fang Bangjiang","doi":"10.1016/j.arr.2026.103025","DOIUrl":"10.1016/j.arr.2026.103025","url":null,"abstract":"<div><div>Sepsis-induced cardiomyopathy (SCM) augments the mortality of sepsis patients. SCM prevention and early monitoring are widely agreed upon, but therapeutic approaches against SCM are challenging to develop primarily due to the complexity of its pathophysiological mechanisms. The fundamental mechanisms contributing to SCM include inflammation, oxidative stress, mitochondrial dysfunction, energy metabolism disorders, disorders of calcium homeostasis, myocardial edema, and cell death. These processes are subject to complex cross-regulatory interactions, forming a pathological network centered on inflammation. Furthermore, this review summarized the efficacy and mechanisms of vasoactive drugs, other pharmacological agents, and natural products in treating SCM, emphasizing emerging therapeutic targets. Advancing the clinical management of SCM requires a shift from interventions focused on single mechanisms to the establishment of a network-based regulatory strategy centered on inflammation. This method may provide innovative solutions for treating SCM.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103025"},"PeriodicalIF":12.4,"publicationDate":"2026-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ageing of human myofibres in the Vastus Lateralis muscle: A narrative review","authors":"Antoneta Granic ,&nbsp;Davina C.M. Simoes ,&nbsp;T. Scott Bowen ,&nbsp;Nessrin Almaghtuf ,&nbsp;Gavin Richardson ,&nbsp;Avan A. Sayer","doi":"10.1016/j.arr.2026.103022","DOIUrl":"10.1016/j.arr.2026.103022","url":null,"abstract":"<div><div>Human skeletal muscle is a complex, dynamic tissue that changes profoundly with age. It comprises heterogenous cells including long, contractile, multinucleated myofibres, broadly classified into type I (slow-twitch/oxidative) fibres and type II (fast-twitch/glycolytic) fibres, as well as a variety of mononucleated cells (e.g., immune, satellite, and endothelial cells), and the extracellular matrix (ECM). Ageing as well as sarcopenia, a muscle condition characterised by progressive loss of muscle strength and mass observed mostly in older adults, appear to disproportionately affect type II fibres. In histomorphometric studies of ageing muscle this has been described as type II myofibres loss, fibre atrophy, and redistribution of fibre types, although some inconsistent findings exist. The precise mechanisms underlying this selective vulnerability remains elusive but are likely attributable to dysregulated nutrient sensing contributing to the deregulation of muscle protein synthesis and degradation cycle, and neuromuscular junction, satellite cells, ECM and mitochondrial dysfunction. This narrative review focuses on the <em>Vastus Lateralis</em> (<em>VL</em>) muscle—a major limb muscle involved in locomotion and one of the most extensively studied human skeletal muscles—and summarises key structural and phenotypic changes that occur with ageing at the organ, tissue, and cell levels, and their relevance to sarcopenia. We also briefly discuss external influences of these changes, highlight gaps in knowledge, and suggest future directions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103022"},"PeriodicalIF":12.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The potential of prehabilitation to enhance recovery in sarcopenic and frail older kidney transplant candidates: A narrative review","authors":"Natália Tomborelli Bellafronte ,&nbsp;Guillermina Barril-Cuadrado ,&nbsp;Francesco Carli","doi":"10.1016/j.arr.2026.103021","DOIUrl":"10.1016/j.arr.2026.103021","url":null,"abstract":"<div><h3>Background</h3><div>Older adults represent the fastest-growing segment on kidney transplant (KT) waiting lists. In this population, the high prevalence of sarcopenia and frailty impairs the ability to adapt and respond to metabolic stress, contributing to poorer postoperative outcomes. Given that many adverse events occur in the early postoperative period, the optimal window for intervention is prior to surgery. Prehabilitation, defined as a structured intervention delivered before surgery, aims to enhance postoperative recovery.</div></div><div><h3>Methods</h3><div>In the context of older adults candidates to KT, we constructed a detailed narrative review on: the development of sarcopenia and frailty as a result of ageing and chronic kidney disease pathophysiologic process; sarcopenia and frail influence on post-operative outcomes, and prehabilitation as a strategy to improve recovery.</div></div><div><h3>Results</h3><div>Age-related anabolic resistance and hormonal, cellular and metabolic disarrangements resulting from the pathophysiologic process of kidney failure, aggravated by dialysis side effects, result in sarcopenia and frailty. Frail/sarcopenic older adults are more vulnerable to post-operative complications and recovery is prolonged. Published prehabilitation studies for candidates to KT mostly comprised of in-situ exercise-only interventions; prehabilitated patients demonstrated improvement of physical function as compared to baseline and just one study assessed post-operative outcomes. The limited results from these studies reflect the absence of a multimodal approach with a comprehensive and personalized medical, dietetic and psychosocial intervention in addition to exercise, necessary to accomplish success. Based on renal, ageing and surgical scientific literature, a suggested multimodal prehabilitation program is proposed.</div></div><div><h3>Conclusion</h3><div>Although the optimal structure of prehabilitation remains to be established, individualized multimodal interventions appear to hold promise for optimizing patients during the KT waiting period.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"115 ","pages":"Article 103021"},"PeriodicalIF":12.4,"publicationDate":"2026-01-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145928597","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}