Ageing Research Reviews最新文献

{"title":"Trends and mechanisms of Alzheimer's disease and hearing impairment: A 20-year perspective","authors":"Fen-Fen Li ,&nbsp;Jian-Peng Wang ,&nbsp;Wen-Jie Zhang ,&nbsp;Ping-Ting Zhou ,&nbsp;Min Fan ,&nbsp;Ning-Ning Cai ,&nbsp;Yi-Fan Cai ,&nbsp;Ke Han ,&nbsp;Yi-Pin Yang ,&nbsp;Zi-Yue Fu ,&nbsp;Si-Yue Yin ,&nbsp;Bing-Yu Liang ,&nbsp;Yan-Xun Han ,&nbsp;Ye-Hai Liu ,&nbsp;Bu-Sheng Tong ,&nbsp;Ming-Xu Li ,&nbsp;Yu-Chen Liu","doi":"10.1016/j.arr.2025.102799","DOIUrl":"10.1016/j.arr.2025.102799","url":null,"abstract":"<div><div>Alzheimer’s disease (AD) and hearing loss (HL) are major age-related public health challenges with emerging evidence suggesting their interconnection. This study aimed to investigate global research trends, shared molecular mechanisms, and clinical implications of AD and HL. A total of 349 articles published between 2004 and 2024 were retrieved from the Web of Science Core Collection and analyzed using VOSviewer and CiteSpace. GeneCards and STRING databases were used to explore molecular targets and pathways. Results showed steady growth in publication volume, with the United States and China as leading contributors. Major keywords included “age-related hearing loss”, “cognitive impairment”, and “amyloid plaques”, and “prevention” represent current and forward-looking future research trends and target themes in the field. Key authors and institutions included Doris-Eva Bamiou, University College London, and the University of California system. Molecular analysis identified 2747 genes potentially shared between AD and HL, involved in apoptosis, oxidative stress, inflammation, and metabolic dysregulation. Among them, SLC26A4, CDH23, MYO3A, TMC1, and MYO15A were highlighted as representative targets related to auditory and neurodegenerative processes. The study further distinguished between central and peripheral HL: central HL is closely linked to neuroinflammation and synaptic degeneration, while peripheral HL may contribute to cognitive decline through sensory deprivation. These findings support early auditory screening and tailored intervention strategies, and provide a foundation for multi-target approaches in managing cognitive decline, emphasizing the importance of integrating auditory assessment into precision medicine frameworks for aging populations.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102799"},"PeriodicalIF":12.5,"publicationDate":"2025-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144276996","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":"Long-term fasting and its influence on inflammatory biomarkers: A comprehensive scoping review","authors":"Isabella de Ciutiis ,&nbsp;Shadia Djakovic ,&nbsp;Maria Lastra Cagigas ,&nbsp;Andrius Masedunskas ,&nbsp;Lee Smith ,&nbsp;Claudio Franceschi ,&nbsp;Luigi Fontana","doi":"10.1016/j.arr.2025.102797","DOIUrl":"10.1016/j.arr.2025.102797","url":null,"abstract":"<div><h3>Objectives</h3><div>Despite the rising popularity of prolonged fasting, its biological effects and potential risks remain unclear, with claims suggesting it reduces inflammation. This systematic scoping review examines the impact of prolonged fasting (≥48 h) on key inflammatory biomarkers: C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α).</div></div><div><h3>Methods</h3><div>Following PRISMA-ScR guidelines, a comprehensive search of PubMed, Medline (Ovid), Web of Science, Embase (Classic and Embase), and Scopus was conducted for studies published up to August 2024. Eligible studies were peer-reviewed human clinical trials that investigated prolonged fasting’s effects on inflammatory markers.</div></div><div><h3>Results</h3><div>Following a systematic search across multiple databases, 14 studies met the inclusion criteria. Contrary to popular belief, the majority of studies reported either no change or an increase in inflammatory biomarkers during prolonged fasting. CRP levels frequently rose—often significantly—during fasting periods, particularly in individuals with overweight or obesity. Some studies also reported increases in TNF-α and IL-6, though results were less consistent. Importantly, several studies showed a reduction or normalization of CRP levels after refeeding, suggesting that the inflammatory response to fasting may be transient or adaptive. These discrepancies may be due to differences in fasting duration, participant characteristics, and study design.</div></div><div><h3>Conclusions</h3><div>This review finds limited and inconsistent evidence on prolonged fasting's effects on inflammation, with varied study designs and lack of standard protocols. Overall, prolonged fasting appears to lead to an increase in inflammation that may represent an adaptive mechanism. Future research, particularly randomized controlled trials, is needed to assess the long-term impacts of fasting on inflammation and metabolic diseases across different populations.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102797"},"PeriodicalIF":12.5,"publicationDate":"2025-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144243028","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":"Exploring the impact of community-based interventions on healthy older adults’ physical health, psychological wellbeing, and social connections: A systematic review","authors":"Shaimaa Elhag,&nbsp;Malwina A. Niechcial,&nbsp;Lauren Potter,&nbsp;Alan J. Gow","doi":"10.1016/j.arr.2025.102784","DOIUrl":"10.1016/j.arr.2025.102784","url":null,"abstract":"<div><h3>Background</h3><div>Given trends towards greater life expectancy, there is an increasing need to promote healthy ageing and add quality and value to older adults’ lives, however, the evidence regarding the effects on overall health and wellbeing has not been synthesised. Active lifestyles may provide diverse health and wellbeing benefits for older adults in terms of maintaining or improving their physical, psychological and social functions. This systematic review evaluates whether and how different types of interventions within community-based settings could benefit specific aspects of older adults’ health and wellbeing.</div></div><div><h3>Methods</h3><div>PubMed, PsycINFO, Scopus and Web of Science were systematically searched in January 2022 for experimental studies (including randomised controlled trials, non-randomised controlled trials, and quasi-experimental studies) exploring health and wellbeing benefits of community-based activities in older adults. A total of 12,707 sources were identified through database searches with 183 retained for full screening. Final inclusion was based on the following eligibility criteria: (1) participants were generally healthy and predominantly independent community-dwelling older adults aged 60 and above; (2) interventions were based in real-world settings, e.g., dance, art and technology classes, etc. held in publicly-accessible facilities; (3) pre-/post-interventions assessed at least one outcome in physical health, psychological wellbeing or social connections; (4) control groups were used, including passive and active control groups or groups that received a different type of intervention; (5) experimental studies followed a quantitative research design. Study quality was systematically assessed, and a comprehensive narrative synthesis of the findings was conducted.</div></div><div><h3>Results</h3><div>Of the 183 studies screened, 56 were included in the final review. Among the 33 predominantly physical interventions, 31 demonstrated positive effects. Of the 16 predominantly mental interventions, 14 reported benefits. All seven predominantly social interventions reported positive effects.</div></div><div><h3>Discussion</h3><div>The benefits of real-world interventions were reported across a range of outcomes, particularly in terms of reducing depression or anxiety, or improving physical functioning, sleep quality and social participation. However, heterogeneity in interventions, sample design, duration and dosage suggest that more research is needed to clarify how intervention exposure benefits health and wellbeing. As real-world interventions more closely resemble the way in which older people engage in activities, evidence of their effectiveness in promoting health and wellbeing should inform preventative healthcare provision and policymaking.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"111 ","pages":"Article 102784"},"PeriodicalIF":12.5,"publicationDate":"2025-06-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144251233","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 role of secretory autophagy and exosomes in the accumulation of drusen during the development of age-related macular degeneration (AMD)","authors":"Juha M.T. Hyttinen ,&nbsp;Minna Niittykoski ,&nbsp;Kai Kaarniranta","doi":"10.1016/j.arr.2025.102796","DOIUrl":"10.1016/j.arr.2025.102796","url":null,"abstract":"<div><div>Age-related macular degeneration (AMD) is the most common disease of the elderly that leads to the loss of sight. So far, no satisfactory therapy exists for this complex eye disease. The appearance of extracellular deposits, called drusen, on the outside of the retinal pigment epithelium (RPE) is considered to be the main clinical hallmark of AMD. Whilst the mechanisms of drusen formation are not well known, secreted material from the RPE, during its degeneration, is thought to contribute to the development of AMD. Various unconventional protein secretion (UPS) pathways are considered to be routes for the delivery of material which form the drusen. The two main forms of UPS are secretory autophagy, which is responsible for the cleansing of cellular debris from the RPE cells and endosomal secretion which carries material outside of the cell via exosomes. These pathways are unconventional in the sense that they comprise the delivery of material to the exterior of cells by bypassing the Golgi apparatus. Although secretory autophagy and exosome release are regarded as different routes by which cells exude material, they share similarities, such as common molecular participants and that their routes converge. Therefore, manipulation of these two processes might be useful in a therapy against AMD by diminishing the destructive drusen progression in the vicinity of the RPE.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102796"},"PeriodicalIF":12.5,"publicationDate":"2025-06-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144222904","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":"Temporal trends in the incidence of intracerebral hemorrhage from 1992 to 2021: An age-period-cohort analysis based on the global burden of disease study 2021","authors":"Yunyi Hao ,&nbsp;Xue Xia ,&nbsp;Jinqiao Zhu ,&nbsp;Weizi Yang ,&nbsp;Xingquan Zhao ,&nbsp;Anxin Wang","doi":"10.1016/j.arr.2025.102789","DOIUrl":"10.1016/j.arr.2025.102789","url":null,"abstract":"<div><h3>Objective</h3><div>To explore the temporal trends of intracerebral hemorrhage (ICH) incidence from 1992 to 2021 and the heterogeneity across age groups, sexes, and socio-demographic index (SDI) levels.</div></div><div><h3>Methods</h3><div>Data on ICH incidence were extracted from the Global Burden of Disease Study 2021. Joinpoint regression was utilized to calculate the average annual percentage change (AAPC). The slope index of inequality and concentration index were utilized to quantify the health inequality. The age-period-cohort (APC) model was applied to estimate the net/local drifts and age/period/cohort effects on ICH incidence.</div></div><div><h3>Results</h3><div>From 1992 to 2021, ICH incidence increased from 2471,769 to 3444,338 cases worldwide, while the age-standardized incidence rate (ASIR) per 100,000 individuals decreased from 59.60 to 40.83 with an AAPC of 1.33 % and a non-monotonic tendency of initial decline (1992–2014), subsequent increase (2014–2019), and further decline (2019–2021). Females decreased faster than males, and countries with higher SDI experienced a quicker decline. Health inequalities have been relieved, and ICH cases cluster in higher SDI countries. The APC analysis indicates the rise in incidence with increasing age and favorable period/cohort effects globally and in five SDI regions. The decline in males primarily occurred in aged population, whereas for females, it was mainly in young and middle-aged adults.</div></div><div><h3>Conclusion</h3><div>There was a downward trend in global ICH incidence from 1992 to 2021. Economically developed countries must remain vigilant against the rise in ICH cases due to aging. For males, primary prevention should target the younger adults, whereas for females, it should target aged population.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102789"},"PeriodicalIF":12.5,"publicationDate":"2025-06-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144212497","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":"Unlocking the potential of histone deacetylase inhibitors in combatting age-related retinal degenerative diseases","authors":"Bo Liu ,&nbsp;Minglu Wang ,&nbsp;Ning Pu ,&nbsp;Jiale Wang ,&nbsp;Wenhui Fan ,&nbsp;Chengkang Qu ,&nbsp;Hao Wu ,&nbsp;Zongming Song ,&nbsp;Ye Tao","doi":"10.1016/j.arr.2025.102788","DOIUrl":"10.1016/j.arr.2025.102788","url":null,"abstract":"<div><div>Retinal degeneration (RD), a group of progressive diseases marked by the loss of retinal neurons. Aging contributes to the gradual decline in cellular function, which, in turn, exacerbates the pathogenesis of RD through complex molecular mechanisms, including aberrant gene expression, impaired cellular signaling pathways, oxidative stress, and inflammation. The pivotal role of epigenetic histone modifications in mediating the onset and progression of neurological disorders has garnered increasing attention, especially concerning histone acetylation. The level of histone acetylation is regulated by histone acetyltransferases (HATs) and histone deacetylases (HDACs). HATs and HDACs can enzymatically modify lysine residues on histones or non-histones via adding or removing acetyl groups, leading to changes in transcriptional activity. Histone deacetylase inhibitors (HDACis) can interfere with the deacetylase activity of HDACs, enhance the level of both histone and non-histone acetylation, and exert a regulatory influence on gene transcription. Accumulating evidence supports the role of HDACis in the treatment of multiple medical conditions beyond cancer, renewing interest in their potential applications in age-related diseases. In this context, HDAC inhibition represents a novel approach for mitigating the age-related cellular dysfunctions contributing to RD. HDACis hold promise in addressing these pathological processes and preserving retinal function through targeting HDACs. We intend to elucidate the neuroprotective effects of common HDACis on age-related RD, with a focus on their role in counteracting the detrimental effects of aging, and provide a comprehensive summary of the efficacy of HDACis in both animal models and clinical trials for age-related RD. These findings would enrich our understanding of HDACis and promote their future applications in the treatment of age-related RD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102788"},"PeriodicalIF":12.5,"publicationDate":"2025-05-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144210460","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":"“Aging and epigenetic implications in radiotherapy: The promise of BNCT”","authors":"Chiara Papulino ,&nbsp;Marco Crepaldi ,&nbsp;Gregorio Favale ,&nbsp;Nunzio Del Gaudio ,&nbsp;Rosaria Benedetti ,&nbsp;Angela Nebbioso ,&nbsp;Michele Grieco ,&nbsp;Marco Malavolta ,&nbsp;Jacopo Sabbatinelli ,&nbsp;Annalisa Capuano ,&nbsp;Erika Martinelli ,&nbsp;Giulia Martini ,&nbsp;Valerio Nardone ,&nbsp;Salvatore Cappabianca ,&nbsp;Concetta Ambrosino ,&nbsp;Giuseppe Paolisso ,&nbsp;Lucia Altucci ,&nbsp;Vincenzo Carafa","doi":"10.1016/j.arr.2025.102786","DOIUrl":"10.1016/j.arr.2025.102786","url":null,"abstract":"<div><div>Although cancer treatment strategies have made considerable progress in recent decades, the challenge of selectively killing tumor cells while minimizing damage to healthy tissue remains. Radiotherapy (RT) continues to be crucial for tumor growth control when combined with surgery, chemotherapy, and immunotherapy. RT effectiveness depends on factors such as cancer type, tumor features, and the choice of external or internal treatment. Given its non-invasive nature and low systemic toxicity, RT is a suitable strategy for elderly patients. However, despite its efficacy, variations in cell sensitivity to radiation influence treatment outcomes, and normal cells surrounding the tumor can also be affected. Radiation-induced DNA damage can trigger cellular senescence, a permanent cell cycle arrest with a pro-inflammatory secretory phenotype, contributing to tissue damage in healthy cells and radio-resistance in tumor cells. RT causes not only DNA breakage but also epigenetic remodeling. Epigenetic pathways are involved in RT response, and the radiosensitivity of tumor cells can be modulated using epigenetic compounds. Emerging treatments based on more precise forms of RT, such as boron neutron capture therapy (BNCT), offer promising results by selectively targeting tumors while potentially preserving healthy tissues. BNCT has shown efficacy in glioblastoma, recurrent head and neck carcinoma, and melanoma. This review i) examines the mechanisms and challenges of conventional RT, focusing on aging and its role in treatment efficacy and tolerability, ii) describes the impact of senescence and epigenetic factors on resistance, iii) explores advances in BNCT, and iv) considers the potential of epigenetic drugs to optimize RT outcomes.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102786"},"PeriodicalIF":12.5,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144200977","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 memory- and cognition-facilitating effects of spermidine in aging and aging-related disorders","authors":"Mengjie Zou ,&nbsp;Dan Li ,&nbsp;Yi Yang","doi":"10.1016/j.arr.2025.102787","DOIUrl":"10.1016/j.arr.2025.102787","url":null,"abstract":"<div><div>Spermidine is a natural polyamine found in living organisms. In human, the level of spermidine declines with aging. Emerging lines of evidence indicates that supplementation of spermidine favors the improvement of memory performance and cognition function. In this article, recent findings regarding the metabolism of spermidine under pathophysiological conditions are discussed. This review emphasizes the recent mechanistic insights into the memory- and cognition-facilitating effects of spermidine, specifically detailing autophagy induction, mitochondrial protection, synaptic maintenance and other aspects. Recent advances in understanding the precise role of spermidine may shed light on the prevention and treatment of aging-associated memory and cognitive decline.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"109 ","pages":"Article 102787"},"PeriodicalIF":12.5,"publicationDate":"2025-05-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144184652","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":"Effectiveness of virtual reality interventions on quality of life, cognitive function and physical function in older people with Alzheimer's disease: A systematic review","authors":"Edgar Vásquez-Carrasco ,&nbsp;Jordan Hernandez-Martinez ,&nbsp;María Sepúlveda-Ramírez ,&nbsp;Florencia Carmine ,&nbsp;Cristian Sandoval ,&nbsp;Hadi Nobari ,&nbsp;Pablo Valdés-Badilla","doi":"10.1016/j.arr.2025.102785","DOIUrl":"10.1016/j.arr.2025.102785","url":null,"abstract":"<div><div>This systematic review aimed to evaluate and synthesize the scientific evidence of virtual reality (VR) interventions on quality of life, cognitive function, and physical function in older people with Alzheimer's disease (AD). A systematic review search until March 2025 using seven generic databases: PubMed, EBSCOhost, CINAHL Complete, Cochrane, ProQuest, Scopus, and Web of Science. The PRISMA, RoB 2, and GRADEpro tools were used to assess the methodological quality, risk of bias, and certainty of the evidence.The protocol was registered in PROSPERO database, CRD42024629853. Of 3347 records identified across the databases, seven studies were analyzed using the PICOS format. This review included 517 older people with AD (mean age 76.5 years; 57.5 % female). Due to the heterogeneity of the assessment tools, a meta-analysis could not be performed. Although no consistent significant differences were found between the experimental and control groups, several individual studies reported improvements. Specifically, two studies showed improvements in quality of life and cognitive function, while three reported enhancements in physical function. The interventions included immersive cognitive training, exergaming, Kinect-based systems, and Physiomat platforms, with durations ranging from 4 to 16 weeks and frequencies of 2–5 sessions per week. Analysis of the reviewed studies suggests that VR interventions may benefit cognitive function, physical function, and, to a lesser extent, quality of life in older people with AD.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"109 ","pages":"Article 102785"},"PeriodicalIF":12.5,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144176242","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":"In-silico evaluation of aging-related interventions using omics data and predictive modeling","authors":"Georg Fuellen ,&nbsp;Daniel Palmer ,&nbsp;Claudia Fruijtier ,&nbsp;Roberto A. Avelar","doi":"10.1016/j.arr.2025.102777","DOIUrl":"10.1016/j.arr.2025.102777","url":null,"abstract":"<div><div>A major challenge in aging research is identifying interventions that can improve lifespan and health and minimize toxicity. Clinical studies cannot usually consider decades-long follow-up periods, and therefore, in-silico evaluations using omics-based surrogate biomarkers are emerging as key tools. However, many current approaches train predictive models on observational data, rather than on intervention data, which can lead to biased conclusions. Yet, the first classifiers for lifespan extension by compounds are now available, learned on intervention data. Here, we review evaluation methodologies and we prioritize training on intervention data whenever available, highlight the importance of safety and toxicity assessments, discuss the role of standardized benchmarks, and present a range of feature processing and predictive modeling approaches. We consider linear and non-linear methods, automated machine learning workflows, and use of AI. We conclude by emphasizing the need for explainable and reproducible strategies, the integration of safety metrics, and the careful validation of predictors based on interventional benchmarks.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"110 ","pages":"Article 102777"},"PeriodicalIF":12.5,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144922","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}