Ageing Research Reviews最新文献

{"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":"2026-05-01","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":"Blood-based biomarkers for Alzheimer's disease: Advances in early detection and monitoring of age-related neurodegeneration","authors":"Wenting Fu ,&nbsp;Paul Chi-Lui Ho","doi":"10.1016/j.arr.2026.103058","DOIUrl":"10.1016/j.arr.2026.103058","url":null,"abstract":"<div><div>Alzheimer's disease (AD) presents a critical global challenge, accounting for over 60 % of the 57 million current dementia cases worldwide, with prevalence projected to exceed 100 million by 2050. Traditional diagnostic approaches, such as cerebrospinal fluid (CSF) analysis and neuroimaging are constrained by invasiveness, high costs, and limited accessibility, particularly problematic in aging population where early detection is crucial for effective intervention. This review synthesizes recent advances in blood-based biomarkers for AD, specifically phosphorylated tau proteins (p-tau217, p-tau181), neurofilament light chain (NfL), glial fibrillary acidic protein (GFAP), and the amyloid-β42/40 ratio. These minimally invasive biomarkers demonstrate exceptional diagnostic accuracy with p-tau217 achieving AUC values greater 0.93 and 91 % positive predictive value in detecting AD pathology, Critically, these biomarkers can identify pathological changes 15–20 years before symptom onset, with plasma p-tau217 levels increasing over 8.5 % annually during preclinical stages. We propose that dried blood spots (DBS), containing both arterial and venous blood components, offer superior representation of brain-derived substances at their first systematic distribution after cardiac output. Ultrasensitive technologies like Simoa and mass spectrometry now enable femtomolar-level detection, revolutionizing of AD diagnostics. However, challenges persist in assay standardization persist in assay standardization, and population-specific validation. Overcoming these barriers to integrate blood biomarkers with DBS technology represents a transformative shift toward accessible, scalable screening in aging communities, offering a paradigm shift in preventing age-related neurodegeneration through early detection and timely intervention.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"117 ","pages":"Article 103058"},"PeriodicalIF":12.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146147495","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 ethics case for longevity science","authors":"Zhuang Zhuang Han ,&nbsp;João Pedro de Magalhães","doi":"10.1016/j.arr.2026.103054","DOIUrl":"10.1016/j.arr.2026.103054","url":null,"abstract":"<div><div>Recent advances in biogerontology show that ageing is malleable, opening the possibility of delaying chronic disease and extending healthspan. Ethical debate has been dominated by consequentialist framings, balancing potential benefits against fears of overpopulation, inequality, or loss of meaning. We seek to further this discussion by grounding the case for longevity research not only in outcomes but also in respect for autonomy, self-ownership, and the intrinsic value of life itself. On this basis, we address three kinds of critiques: philosophical appeals to “naturalness”, societal concerns about resources, justice and stagnation, and individual worries about meaning and boredom, showing that none provide decisive objections. Beyond rebuttal, we highlight neglected benefits: longevity research drives technological integration like the Apollo program, affirms the priority of existing persons over abstractions, and liberates individuals from rigid age-based expectations. The moral baseline must flip: the burden now falls on defenders of forced ageing to explain why preventable suffering should continue.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"117 ","pages":"Article 103054"},"PeriodicalIF":12.4,"publicationDate":"2026-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146138199","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 neuropathic pain: Mitochondria-to-glia cascade, system mechanisms, and therapeutic strategies","authors":"Shreyasi Majumdar ,&nbsp;Puneet K. Samaiya ,&nbsp;Sukesh Kumar Gupta ,&nbsp;Sairam Krishnamurthy ,&nbsp;Santosh Kumar Prajapati","doi":"10.1016/j.arr.2026.103042","DOIUrl":"10.1016/j.arr.2026.103042","url":null,"abstract":"<div><div>Neuropathic pain (NP) creates a severe pathological condition that primarily affects elderly people because of their accumulated neurobiological changes that make them more susceptible to persistent pain. The aging process leads to multiple mechanisms that combine neurodegeneration with immunosenescence and mitochondrial dysfunction with impaired autophagy and glial priming, and ion channel dysregulation to create a nociceptive environment. This review examines how mitochondrial breakdown and dysfunctional autophagy, and ion channel disturbances with glial cell activation form a interconnected system which makes older people more prone to NP. The review also examines how the neuro–immune–metabolic and gut–brain axis maintain persistent pain across the lifespan while discussing its cellular pathology. Preclinical research shows that aged models develop more severe NP symptoms, yet clinical evidence reveals distinct diagnostic and therapeutic challenges that affect older adults. The review presents current treatment strategies which include mitochondrial protectants and autophagy enhancers together with immunomodulators and microbiome-based interventions, and gene therapies to develop appropriate multimodal therapies for different age group. Further, it combines mechanistic knowledge with translational viewpoints to demonstrate the immediate requirement for treating NP as a geroscience challenge to develop better pain management strategies for older adults.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"116 ","pages":"Article 103042"},"PeriodicalIF":12.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146098528","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":"Corrigendum to “Ageing and liver immune cells” [Ageing Res. Rev. 115 (2026) 103039]","authors":"Jarrod J. Kennedy ,&nbsp;Patrick Bertolino ,&nbsp;Sophie Lucic Fisher ,&nbsp;Meng C. Ngu ,&nbsp;Nicholas J. Hunt ,&nbsp;Peter A.G. McCourt ,&nbsp;Victoria C. Cogger ,&nbsp;David G. Le Couteur","doi":"10.1016/j.arr.2026.103063","DOIUrl":"10.1016/j.arr.2026.103063","url":null,"abstract":"","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"116 ","pages":"Article 103063"},"PeriodicalIF":12.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146229883","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":"NAD⁺ supplementation for anti-aging and wellness: A PRISMA-guided systematic review of preclinical and clinical evidence","authors":"Cory Gallagher ,&nbsp;Owoturo Oluwaseun Emmanuel","doi":"10.1016/j.arr.2026.103057","DOIUrl":"10.1016/j.arr.2026.103057","url":null,"abstract":"<div><div>Nicotinamide adenine dinucleotide (NAD⁺) declines with age, motivating “NAD⁺-boosting” strategies ranging from lifestyle interventions to supplementation with NAD⁺ precursors (e.g., nicotinamide riboside [NR], nicotinamide mononucleotide [NMN]) and, in some wellness settings, parenteral NAD⁺ administration. We conducted a PRISMA-guided systematic review of peer-reviewed human and rodent intervention studies (January 2010–October 2025) evaluating NAD-related compounds administered orally or parenterally. We identified 113 eligible studies: 33 human intervention studies (28 randomized; 5 nonrandomized) and 80 rodent studies. In rodent models, NAD⁺ augmentation was frequently associated with improvements in metabolic, mitochondrial, inflammatory, and functional outcomes, although effects varied across models and endpoints. In humans, oral NR and NMN consistently demonstrated biochemical target engagement (circulating (plasma/whole blood) or cellular (e.g., PBMC) NAD-related metabolites) and were generally well tolerated over weeks to months; however, effects on functional, metabolic, vascular, and other healthspan-relevant outcomes were heterogeneous and often null or endpoint-specific. No eligible outcomes trials evaluated intravenous or intramuscular NAD⁺ itself for anti-aging or wellness indications. One nonrandomized intravenous NMN study met inclusion criteria and primarily contributed short-term safety and biomarker information. An intravenous NAD⁺ pharmacokinetic pilot lacking eligible clinical outcomes was identified as contextual evidence only. Overall, NAD⁺ augmentation shows clear biological activity, but clinical effectiveness for anti-aging or wellness outcomes remains inconclusive. Larger, well-designed randomized trials with longer follow-up and prespecified clinically meaningful endpoints are needed, particularly for parenteral approaches.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"116 ","pages":"Article 103057"},"PeriodicalIF":12.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146144899","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":"Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases","authors":"Nan Chen ,&nbsp;Carmen K. Chan ,&nbsp;Farhan Ullah Khan ,&nbsp;Priya Makhijani ,&nbsp;Taylor R. Valentino ,&nbsp;Shawn Winer ,&nbsp;Cynthia T. Luk ,&nbsp;Daniel A. Winer","doi":"10.1016/j.arr.2026.103036","DOIUrl":"10.1016/j.arr.2026.103036","url":null,"abstract":"<div><div>Age-associated dysbiosis, marked by shifts in the composition of gut microbiota and gut microbiota-derived metabolites (GMDMs), is increasingly implicated in driving systemic low-grade inflammation during aging. The disrupted GMDM pools, including altered levels of short-chain fatty acids (SCFAs), secondary bile acids (BAs) and tryptophan (Trp) metabolites, lead to mucosal barrier dysfunction, immunometabolic dysregulation, and modulation of innate and adaptive immune cells. In turn, this cascade of events drives tissue degeneration, chronic inflammation, and the onset of age-related diseases (ARDs). Here, we summarize the immunomodulatory role of major GMDMs and how aging may increase susceptibility to ARDs through changing GMDMs. We then explore the latest findings linking altered GMDM profiles to immune dysfunction across major gut-organ axes, including the liver, adipose tissue, muscle, and brain. Last, we highlight recent advances in harnessing GMDMs as geromedicine to improve aging parameters and discuss the potential of artificial intelligence (AI) in accelerating the bench-to-bedside translation of GMDM research. Together, this review positions GMDMs as actionable targets in a dysbiosis-driven network of immune aging, offering new possibilities for the development of healthspan-extending precision geromedicine.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"116 ","pages":"Article 103036"},"PeriodicalIF":12.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109082","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":"Blood flow and angiogenesis: Major mechanisms mediating healthful longevity","authors":"Jie Zhang ,&nbsp;Dorothy E. Vatner ,&nbsp;Ahmed Gad ,&nbsp;Robert M. Graham ,&nbsp;Stephen F. Vatner","doi":"10.1016/j.arr.2026.103037","DOIUrl":"10.1016/j.arr.2026.103037","url":null,"abstract":"<div><div>While human lifespan has increased dramatically over the past century, the extension of healthspan, the period free of chronic age-related disease, has lagged behind. Blood flow and angiogenesis are significantly reduced in aging humans, playing a crucial role in mediating cardiovascular disease and heart failure - major causes of reduced lifespan. However, these mechanisms have not been studied as extensively as cellular and molecular mechanisms in animal models. Healthful aging, due to angiogenesis and improved blood flow, is the focus of this review. Here we considered 25 rodent models of healthful longevity. Seven of these had direct evidence of improved blood flow and angiogenesis contributing to enhanced exercise, preserved organ function and resistance to ischemic injury and heart failure. Four others exhibited mixed results, but did not show clearly improved blood flow and angiogenesis Fourteen models did not examine these mechanisms. The mechanisms mediating the improved angiogenesis and, as a result enhanced blood flow, include not only vascular growth hormones and mitochondrial protection, but also a role for a less well studied factor, namely brown adipose tissue (BAT). For example, a recently studied rodent model, the Regulator of G Protein Signaling 14 knockout mouse, exhibited a marked increase in angiogenesis and improved blood flow through a BAT mechanism, i.e., when BAT was removed, blood flow and angiogenesis were no longer improved, but when it was transplanted into wild type mice, blood flow and angiogenesis were enhanced. Given the potential importance of angiogenesis and improved blood flow, these factors need to be considered for future healthful longevity therapeutic translation.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"116 ","pages":"Article 103037"},"PeriodicalIF":12.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146109088","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":"Mitochondrial transfer: A novel mechanism and promising therapeutic strategy in ageing kidney","authors":"Jingge Xu ,&nbsp;Xingyi Li ,&nbsp;Zhiyu Zhang ,&nbsp;Jiahui Wu ,&nbsp;Haiyang Yu ,&nbsp;Yuzheng Wu ,&nbsp;Dan Wang ,&nbsp;Ruixia Bao ,&nbsp;Tao Wang ,&nbsp;Yi Zhang ,&nbsp;Qian Chen","doi":"10.1016/j.arr.2026.103051","DOIUrl":"10.1016/j.arr.2026.103051","url":null,"abstract":"<div><div>As a metabolically active organ, kidney has to challenge progressive functional decline with ageing. Meantime, in the pathogenesis of kidney diseases, renal dysfunction also accelerates an individual’s ageing trajectory, leading to premature senescence and a disconnect between biological age and chronological age. Mitochondrial dysfunction is a well-recognized characteristic of kidney ageing, whereas preserving mitochondrial homeostasis can effectively delay the ageing process. This review summarizes classical alterations in mitochondrial function across renal health and disease, including impaired biogenesis with peroxisome proliferator’s-activated receptor γ coactivator α (PGC-1α) suppression, fission-fusion imbalance with overactivation of dynamin-related protein 1 (DRP1), mitophagy defects linked to abnormalities in the PTEN-induced putative kinase 1 (PINK1)/Parkin pathway, oxidative stress cascades featuring mitochondrial reactive oxygen species (mtROS)-mediated damage, and dysregulation of mitochondrial protein quality control. Moreover, we critically evaluate mitochondrial transfer as novel, non-canonical pathways beyond classical bioenergetics, generally through tunneling nanotubes (TNTs)/ extracellular vesicle-containing mitochondria (EVMs)/ free mitochondrial, and inter-organelle communication. We also discuss alternative mitochondria-targeted therapeutics and dissect their clinical translation hurdles. Appropriate interventions on mitochondrial transfer represents a promising strategy for preventing kidney ageing to maintain long-term renal health and extend lifespan. However, the majority of the studies we reviewed are based on animal and cellular models of other diseases, the relationship between renal ageing and mitochondrial transfer has not been adequately explored in clinical trials, and there is still a long way to go.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"116 ","pages":"Article 103051"},"PeriodicalIF":12.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146127578","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":"Microglial metabolic reprogramming in Alzheimer's disease: Pathways, mechanisms, and therapeutic implications","authors":"Feng-ge Yang ,&nbsp;He Yang ,&nbsp;Sheng-wang Han ,&nbsp;Jun-ting Wang ,&nbsp;Wei Gao ,&nbsp;Qiu-yan Ye ,&nbsp;Miao-miao Zhang ,&nbsp;Yu Yang ,&nbsp;Hong-lin Li","doi":"10.1016/j.arr.2026.103050","DOIUrl":"10.1016/j.arr.2026.103050","url":null,"abstract":"<div><div>In recent years, the immune metabolism of central nervous system cells has gained increasing attention from researchers. Microglia (MG) are innate immune cells of the central nervous system. They can metabolize a wide range of energy substrates. The pathways and products generated through these processes play a critical role in the onset and progression of Alzheimer’s disease (AD). This paper provides a comprehensive review of metabolic reprogramming in MG during AD. It focuses on the three primary energy substrates: glucose, fatty acids, and amino acids. It delves deeply into the molecular signaling pathways that regulate this reprogramming, including TREM2, PI3K-AKT-mTOR, HIF-1α, AMPK, PPARs, and LXRs. Additionally, the paper explores the potential of metabolomics as a tool for early diagnosis of AD, identifying biomarkers that could enhance detection in its early stages. Therapeutic strategies targeting the regulation of microglial phagocytic function, mitochondrial activity, and glycolysis are also examined, highlighting their potential to alleviate disease progression. This review article aims to uncover the dynamic network of microglial metabolic reprogramming. It also explores its causal relationship with the pathological cascade of AD. The findings provide theoretical support for developing innovative drugs that combine metabolic regulation and neuroprotective functions.</div></div>","PeriodicalId":55545,"journal":{"name":"Ageing Research Reviews","volume":"116 ","pages":"Article 103050"},"PeriodicalIF":12.4,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146133752","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}