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Enhancing cognition: The power of neuroplasticity 增强认知:神经可塑性的力量
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-26 DOI: 10.1016/j.arr.2025.102882
Iqra Mukhtar, Kanwal Iftikhar
{"title":"Enhancing cognition: The power of neuroplasticity","authors":"Iqra Mukhtar,&nbsp;Kanwal Iftikhar","doi":"10.1016/j.arr.2025.102882","DOIUrl":"10.1016/j.arr.2025.102882","url":null,"abstract":"<div><div>Cognitive enhancement and neuroplasticity are interconnected terms. Neuroplasticity is an intrinsic brain capability that enables it to adapt and learn throughout life. It involves significant reorganization of neural circuits which is evident not only during normal human development but also occurs following early injury. As aging exerts a detrimental effect on various bodily systems, the extent of neuroplasticity also declines considerably. Recent evidences emphasize that cognitive enhancement can lead to positive neuroplastic changes. Moreover, neuroplastic mechanisms can be harnessed for therapeutic purposes in clinical populations in an effective manner. This approach can also pave a way for cognitive reserve and healthy aging, facilitating the protection against age-associated cognitive impairment and development of neurodegenerative disorders. However, there is an urgent need for more rigorous scientific methods to assess the effectiveness of these interventions, which is crucial for progressing in this area. In this review we aim to illuminate the promising potential of plastic processes in the nervous system. The integrated approach, combining neuromodulatory techniques such as brain stimulation with cognitive enhancement methods, is intriguing and could offer a new avenue for enhancing cognitive functions. Overall, this paper lays the groundwork for further exploration and emphasizes the importance of developing effective interventions that leverage the brain's capacity for change. Future research must refine the methodologies used to measure outcomes, ensure generalization and practical applicability, and develop strategies for implementation in real-world settings. This will ultimately enhance our understanding of how to optimize cognitive health throughout the lifespan.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102882"},"PeriodicalIF":12.4,"publicationDate":"2025-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916990","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}
引用次数: 0
Nucleoside reverse transcriptase inhibitors as a therapeutic opportunity to counteract inflammaging and age-related diseases: New evidence from epidemiological data 核苷逆转录酶抑制剂作为对抗炎症和年龄相关疾病的治疗机会:来自流行病学数据的新证据
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-23 DOI: 10.1016/j.arr.2025.102878
Fabiola Olivieri , Angelica Giuliani , Massimiliano Bonafè
{"title":"Nucleoside reverse transcriptase inhibitors as a therapeutic opportunity to counteract inflammaging and age-related diseases: New evidence from epidemiological data","authors":"Fabiola Olivieri ,&nbsp;Angelica Giuliani ,&nbsp;Massimiliano Bonafè","doi":"10.1016/j.arr.2025.102878","DOIUrl":"10.1016/j.arr.2025.102878","url":null,"abstract":"<div><div>Nucleoside Reverse Transcriptase Inhibitors (NRTIs), widely used to treat HIV and hepatitis B, have recently been shown to possess anti-inflammatory properties by inhibiting inflammasome activation. Epidemiological studies have revealed a significantly reduced incidence of age-related diseases, such as Alzheimer’s disease (AD) and type 2 diabetes mellitus (T2DM), among patients chronically treated with NRTIs, but not with other classes of antiretroviral drugs. In this short review, we explore the mechanistic and clinical evidence linking NRTIs to reduced inflammaging, with particular attention to their effects on endogenous retroelements such as LINEs, SINEs and human endogenous retroviruses (HERVs). These elements, increasingly active with age, contribute to sterile inflammation and disease progression. NRTIs may mitigate this process by blocking reverse transcriptase-dependent formation of RNA:DNA hybrids and other immunostimulatory nucleic acid species. Although mitochondrial toxicity has been a concern, it mainly applies to older NRTIs and is much less pronounced with newer, safer compounds. NRTIs thus represent a compelling case for drug repurposing in the context of age-related diseases. Efforts should be devoted to developing new drugs that overcome NRTIs side effects and retain the anti-inflammaging properties of the parent drugs.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102878"},"PeriodicalIF":12.4,"publicationDate":"2025-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144902721","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}
引用次数: 0
Personalized cognitive enhancement for older adults: An aging-friendly closed-loop human-machine interface framework 面向老年人的个性化认知增强:一个对老年人友好的闭环人机界面框架
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-22 DOI: 10.1016/j.arr.2025.102877
Sa Zhou , Yang Liu , Adam Turnbull , Cristiano Tapparello , Ehsan Adeli , F. Vankee Lin
{"title":"Personalized cognitive enhancement for older adults: An aging-friendly closed-loop human-machine interface framework","authors":"Sa Zhou ,&nbsp;Yang Liu ,&nbsp;Adam Turnbull ,&nbsp;Cristiano Tapparello ,&nbsp;Ehsan Adeli ,&nbsp;F. Vankee Lin","doi":"10.1016/j.arr.2025.102877","DOIUrl":"10.1016/j.arr.2025.102877","url":null,"abstract":"<div><div>Emerging digitally delivered non-pharmacological interventions (dNPIs) offer scalable, low-risk solutions for enhancing cognitive function in older adults, yet their effectiveness remains inconsistent due to a lack of personalization and precise mechanisms of action. Generic, population-based designs often fail to predict individual gains, underscoring the need for more tailored approaches. To address this, we propose a closed-loop human-machine interface (HMI) framework for personalizing dNPIs by optimizing the engagement of neurocognitive resources for cognitive enhancement. Our framework tackles three major challenges: (1) comprehensive and effective neurobehavioral representations for cognitive decoding, (2) tailoring interventions for domain-specific cognitive processes, and (3) ensuring aging-friendly design on usability, validity, and reliability for long-term adherence. We provide reviews and perspectives to guide the development of closed-loop HMIs by outlining the operational details of three key components—sensor, controller, and external actuator—that monitor, analyze, and modulate neurobehavioral activities through real-time adaptive interventions. Centering on neurobehavioral characteristics of older adults, we propose to advance closed-loop HMIs toward (1) deploying multimodal sensor network that captures activities from both central and peripheral nervous systems, (2) artificial intelligence (AI)-powered cognitive decoding and modulation that integrates multi-modal easy-to-acquire neurobehavioral signals and predicts the cross-modal harder-to-acquire signals, and (3) targeting neurobehavioral processes via internal and/or external regulation. We envision that the proposed closed-loop HMI framework could provide personalized dNPI with enhanced effectiveness and scalability for cognitive enhancement in older adults, promoting brain resilience and healthy longevity in the aging population.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102877"},"PeriodicalIF":12.4,"publicationDate":"2025-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144903903","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}
引用次数: 0
Quantum dots in neurotheranostics for the treatment of Alzheimer’s disease 量子点在神经治疗阿尔茨海默病中的应用
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-20 DOI: 10.1016/j.arr.2025.102876
Tripti Sharma , Bushra Bashir , Prince Sharma , Nandani Andotra , Sachin Kumar Singh , Thakur Gurjeet Singh , Sukriti Vishwas
{"title":"Quantum dots in neurotheranostics for the treatment of Alzheimer’s disease","authors":"Tripti Sharma ,&nbsp;Bushra Bashir ,&nbsp;Prince Sharma ,&nbsp;Nandani Andotra ,&nbsp;Sachin Kumar Singh ,&nbsp;Thakur Gurjeet Singh ,&nbsp;Sukriti Vishwas","doi":"10.1016/j.arr.2025.102876","DOIUrl":"10.1016/j.arr.2025.102876","url":null,"abstract":"<div><div>Age-related neurodegeneration is one of the primary causes associated with the pathogenesis of Alzheimer's disease (AD). Currently, there are 5.8 million cases of AD worldwide. With the advancement in technology, the paradigm of treating the disease has shifted from one treatment or diagnosis to simultaneously diagnosing as well as treating the disease. Excellent efforts have been made by the scientists towards the development of nanotheranostics. Among them, quantum dots (QDs) have shown promising results due to their nanometer size, which enables them to cross the blood-brain barrier (BBB) and optical properties which help in imaging the environment/pathology inside the brain. Furthermore, their functionalization with the specific biomolecules or coupling with aptamers/proteins/peptides/antibodies offers site-specific detection of pathological biomarkers. The long-lasting, tunable, and strong fluorescence generated by them within the body helps in the selective detection of biomarkers at very low concentrations. This helps in the accurate and early diagnosis of AD. Their multiplexed sensing of multiple markers at a time due to the tunable property of their emission wavelengths, makes it a more specific and sensitive tool over microarray or other assays. Additionally, real-time tracking of drug delivery and parallel treatment of the disease at the targeted site make them a unique theranostic tool over other techniques. This review consolidates recent advances in QDs-based approaches, encompassing their physicochemical properties, blood–brain barrier (BBB) penetration strategies, synthesis, and functionalization techniques. The roles in targeted drug delivery, bioimaging, and biomarker detection, as well as their intrinsic therapeutic actions, including inhibition of amyloid beta formation and tau aggregation, antioxidative effects, and neuroprotection, have also been discussed. Multiple preclinical studies demonstrate the ability of QDs to enhance drug stability, improve BBB transport, enable high-sensitivity imaging of AD biomarkers, and modulate neuroinflammatory responses.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102876"},"PeriodicalIF":12.4,"publicationDate":"2025-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144887403","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}
引用次数: 0
Non-histone lysine lactylation: Emerging roles in tumor biology and therapeutic implications 非组蛋白赖氨酸乳酸化:在肿瘤生物学和治疗意义中的新作用。
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-17 DOI: 10.1016/j.arr.2025.102875
Qu Zhang , Bo Luo , Xinchen Sun , Hiroaki Nagashima , Yemei Wu , Gai Liang , Yan Luo , Ryohei Sasaki , Qin Qin
{"title":"Non-histone lysine lactylation: Emerging roles in tumor biology and therapeutic implications","authors":"Qu Zhang ,&nbsp;Bo Luo ,&nbsp;Xinchen Sun ,&nbsp;Hiroaki Nagashima ,&nbsp;Yemei Wu ,&nbsp;Gai Liang ,&nbsp;Yan Luo ,&nbsp;Ryohei Sasaki ,&nbsp;Qin Qin","doi":"10.1016/j.arr.2025.102875","DOIUrl":"10.1016/j.arr.2025.102875","url":null,"abstract":"<div><div>Lactate, a byproduct of glycolysis, was first identified to induce a novel post-translational modification (PTM) known as lysine lactylation (Kla) in 2019. Kla has been shown to regulate various biological processes, including transcription, metabolism, cell proliferation, and inflammatory responses, which are pivotal in both tumorigenesis and cellular aging. Initially, Kla was identified as an epigenetic marker on histones, where it regulates gene transcription. However, more recent studies have demonstrated widespread Kla modifications on non-histone proteins, suggesting their involvement in multiple tumorigenic processes, which are often dysregulated during aging. Unlike histone Kla, which influences gene accessibility and transcription, non-histone protein Kla exerts a more direct influence on protein levels and functions by modifying their stability, activity, or localization. This review summarizes the latest advances in non-histone Kla research, highlighting its regulatory factors and role in tumor biology and treatment resistance. Additionally, we discuss the potential implications of non-histone Kla in tumor diagnosis, prognosis, and targeted therapy.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102875"},"PeriodicalIF":12.4,"publicationDate":"2025-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144877164","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}
引用次数: 0
Platelets: A new therapeutic target for neurological diseases 血小板:神经系统疾病的新治疗靶点
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-15 DOI: 10.1016/j.arr.2025.102874
Xin-Xin Wei , Xiao-Qing Tang
{"title":"Platelets: A new therapeutic target for neurological diseases","authors":"Xin-Xin Wei ,&nbsp;Xiao-Qing Tang","doi":"10.1016/j.arr.2025.102874","DOIUrl":"10.1016/j.arr.2025.102874","url":null,"abstract":"<div><div>Beyond their classical roles in hemostasis and coagulation, accumulating evidence highlights platelets as multifaceted regulators within the nervous system. Research has revealed that platelet-derived factors promote blood-brain barrier (BBB) maturation and angiogenesis via neurochemical pathways. At the same time, platelet-rich plasma (PRP) facilitates neural regeneration by mitigating the neurotoxicity of amyloid-beta (Aβ) and activating the PI3k/Akt signaling pathway. Platelets also modulate synaptic plasticity through NMDA receptor-dependent mechanisms and regulate the synthesis of neurotransmitters. Pathologically, platelets emerge as key contributors to neurodegeneration. They exacerbate Alzheimer's disease (AD) pathology by releasing Aβ and promoting tau hyperphosphorylation, trigger migraines via P2Y12-mediated platelet-leukocyte aggregates and serotonin dysregulation, and amplify neuroinflammation in multiple sclerosis (MS) through CD40L-dependent BBB disruption. Conversely, inhibiting platelet activation using PAFR antagonists (Ginkgolide B), P2Y12 inhibitors (Clopidogrel), or cyclooxygenase modulators (Aspirin) can alleviate neuroinflammation, reduce pathological protein accumulation, and promote functional recovery. This review summarizes the mechanistic roles of platelets in both nervous system physiology and neuropathology, proposing novel platelet-targeted preventive and therapeutic strategies.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102874"},"PeriodicalIF":12.4,"publicationDate":"2025-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144865068","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}
引用次数: 0
L-deprenyl extends lifespan across mammalian species: A meta-analysis of 22 longevity experiments l -去戊烯醇延长哺乳动物的寿命:22项长寿实验的荟萃分析
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-13 DOI: 10.1016/j.arr.2025.102873
Michael R. Bene
{"title":"L-deprenyl extends lifespan across mammalian species: A meta-analysis of 22 longevity experiments","authors":"Michael R. Bene","doi":"10.1016/j.arr.2025.102873","DOIUrl":"10.1016/j.arr.2025.102873","url":null,"abstract":"<div><div>Identifying interventions that reproducibly extend lifespan is a central aim in geroscience, with hopes of translating these findings to enhance the health and longevity of older adults. L-deprenyl, an FDA approved medication, has been investigated for its role in aging for over three decades. To evaluate the effect of L-deprenyl on lifespan in mammals we performed a random-effects meta-analysis on 22 rodent lifespan experiments. The results indicate L-deprenyl significantly increases average lifespan with moderate effect size (SMD = 0.6773, p = 0.0002). We identified no significant evidence of publication bias in the examined studies, but did observe substantial heterogeneity. Accounting for experimental factors revealed significant effects of dose (p = 0.0233) and age at initiation (p &lt; 0.0001), with higher doses and older age associated with larger effects. Assessment of treatment effects by mean lifespan of controls suggests short-lived controls are not responsible for the observed effects. In addition to the meta-analysis, we reanalyzed a dog survival study by Ruehl et al. When accounting for age at enrollment and sex, the study no longer displayed a significant effect on survival, though power was limited by small sample size. Together, this analysis of 23 L-deprenyl lifespan experiments spans 27 years of research in 6 countries, 8 strains of rodents, 4 species, 6 doses, and 2 delivery methods, providing some of the most comprehensive data supporting the effect of a compound on lifespan in mammals. Future clinical studies examining L-deprenyls effects on health outcomes in older adults will be critical to determine the translatability of these findings.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102873"},"PeriodicalIF":12.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852972","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}
引用次数: 0
Understanding the influence of TLR-mediated immune system on necroptosis-induced neurodegeneration in Parkinson’s disease 了解tlr介导的免疫系统对帕金森病坏死诱导的神经变性的影响
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-13 DOI: 10.1016/j.arr.2025.102872
Vaishnavi Suresh Jadhav, Dharmendra Kumar Khatri
{"title":"Understanding the influence of TLR-mediated immune system on necroptosis-induced neurodegeneration in Parkinson’s disease","authors":"Vaishnavi Suresh Jadhav,&nbsp;Dharmendra Kumar Khatri","doi":"10.1016/j.arr.2025.102872","DOIUrl":"10.1016/j.arr.2025.102872","url":null,"abstract":"<div><div>Neurodegeneration is a hallmark of various neurological disorders, including Parkinson’s disease (PD), Alzheimer’s disease (AD), stroke, and neurotropic viral infections. Although the precise etiology remains unclear, multiple pathological mechanisms contribute to disease progression, including mitochondrial dysfunction, protein aggregation, calcium excitotoxicity, endoplasmic reticulum (ER) stress, oxidative stress, immune system activation, and neuroinflammation. Among these, the immune response plays a crucial role in disease pathogenesis, acting as a defense mechanism against damage-associated molecular patterns (DAMPs), pathogen-associated molecular patterns (PAMPs), and toxic molecular species. Chronic immune activation, particularly of microglia, is a defining feature of neuroinflammation, which involves both innate and adaptive immune responses. In the central nervous system (CNS), microglia-mediated neuroinflammation leads to the release of proinflammatory cytokines, exacerbating neuronal damage. Necroptosis, a regulated form of programmed cell death, has been implicated in neuroinflammatory disorders, including PD. Persistent microglial activation in response to aggregated proteins stimulates various microglial receptors, which includes Toll-like receptor 4 (TLR4), that play a pivotal role in necroptosis activation via the myeloid differentiating primary response gene 88 (MYD88)-independent pathway. This review explores how immune system-mediated receptor activation triggers cell death pathways, with a focus on TLR-induced necroptosis in PD. In addition, we also discuss various downstream molecular mechanisms linking TLR signaling to necroptosis and discuss the potential of TLRs as therapeutic targets, offering insights for developing neuroprotective strategies in neurodegenerative diseases (NDDS).</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102872"},"PeriodicalIF":12.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852976","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}
引用次数: 0
Biomarkers of multimorbidity: A systematic review 多病的生物标志物:系统综述。
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-13 DOI: 10.1016/j.arr.2025.102870
Maria Beatrice Zazzara , Federico Triolo , Leonardo Biscetti , Ersilia Paparazzo , Marco Fiorillo , Davide Liborio Vetrano , Graziano Onder , on behalf of the BIO-SIGN Study Investigators
{"title":"Biomarkers of multimorbidity: A systematic review","authors":"Maria Beatrice Zazzara ,&nbsp;Federico Triolo ,&nbsp;Leonardo Biscetti ,&nbsp;Ersilia Paparazzo ,&nbsp;Marco Fiorillo ,&nbsp;Davide Liborio Vetrano ,&nbsp;Graziano Onder ,&nbsp;on behalf of the BIO-SIGN Study Investigators","doi":"10.1016/j.arr.2025.102870","DOIUrl":"10.1016/j.arr.2025.102870","url":null,"abstract":"<div><div>The development of multiple chronic diseases in the same individual (i.e., multimorbidity) results from the loss of homeostasis across several biological systems. Identifying pathophysiological pathways common to multiple diseases, using accessible biomarkers, could increase our understanding of multimorbidity and improve its prognostication and management. We conducted a systematic review of peer-reviewed articles published till September 2024 that investigated biomarkers of multimorbidity. Due to study heterogeneity, a synthesis without meta-analysis was performed on 43 studies employing harvest plots based on direction of effect, sample size and study quality. Findings highlight how inflammatory and metabolic biomarkers, such as interleukin-6 (IL-6) and glycated haemoglobin (HbA1c) especially, but also triglycerides, low-density lipoprotein (LDL) cholesterol and kidney and liver markers, along with markers of neurodegeneration including Neurofilament Light Chain (NfL) and Phospho-Tau 217 (p-tau 217), were directly associated with multimorbidity. Nonetheless, evidence for hormonal and vascular activation markers, as well as more novel geroscience biomarkers, remains limited. These markers could have a key role in identifying individuals at high risk of developing or worsening multimorbidity. The review also highlights how methodological challenges, including heterogeneity in study design, populations, and multimorbidity definitions, impact on comparability and generalizability of findings. Addressing these gaps through standardized, longitudinal studies and multi-omics approaches is crucial to improve our understanding of the pathophysiological mechanisms of multimorbidity. In summary, this review outlines the independent association of diverse biomarkers with multimorbidity, opening to the possibility of identifying specific pathophysiological pathways for risk stratification and possible target of future personalized interventions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102870"},"PeriodicalIF":12.4,"publicationDate":"2025-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144859978","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}
引用次数: 0
From clock to clock: Therapeutic target discovery for aging and age-related diseases 从时钟到时钟:发现衰老和年龄相关疾病的治疗靶点
IF 12.4 1区 医学
Ageing Research Reviews Pub Date : 2025-08-12 DOI: 10.1016/j.arr.2025.102871
Jianjiu Chen , Geoffrey Ho Duen Leung , Howell Leung , Alina Ustiugova , Anastasia Shneyderman , Mike Korzinkin , David Gennert , Frank W. Pun , Alex Aliper , Feng Ren , Alex Zhavoronkov
{"title":"From clock to clock: Therapeutic target discovery for aging and age-related diseases","authors":"Jianjiu Chen ,&nbsp;Geoffrey Ho Duen Leung ,&nbsp;Howell Leung ,&nbsp;Alina Ustiugova ,&nbsp;Anastasia Shneyderman ,&nbsp;Mike Korzinkin ,&nbsp;David Gennert ,&nbsp;Frank W. Pun ,&nbsp;Alex Aliper ,&nbsp;Feng Ren ,&nbsp;Alex Zhavoronkov","doi":"10.1016/j.arr.2025.102871","DOIUrl":"10.1016/j.arr.2025.102871","url":null,"abstract":"<div><div>The aging population worldwide necessitates the development of novel therapeutics that enhance the quality of life by preventing and treating age-related diseases. In this review, we first discuss the advantages of a dual-purpose target identification strategy for aging and age-related diseases, with assessment of the hallmarks of aging as an approach to identify such dual-purpose targets. Resulting from a convergence of aging research with machine learning (ML) and other artificial intelligence (AI) models, aging clocks were initially developed as aging biomarkers, but its value in identifying therapeutic targets is also increasingly recognized. Building on recently published aging clocks, we reestablish a significant proportion of known drug targets by identifying clock-associated genes, highlighting the potential of these clocks for target identification. Lastly, we discuss other applications of aging clocks in drug development such as population stratification and disease and treatment monitoring. With the growing availability of multi-omics data and rapid advancements in ML and AI, we anticipate accelerated progress in aging clock research, paving the way for innovative treatments to meet the healthcare needs of a global aging population.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"112 ","pages":"Article 102871"},"PeriodicalIF":12.4,"publicationDate":"2025-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144841639","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}
引用次数: 0
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