Aging and Disease最新文献

{"title":"Rapamycin Attenuates Age-Related Changes in Marmoset Submandibular Gland: A Non-Human Primate Model of Human Oral Aging.","authors":"Parveez Ahamed Abdul-Azees, Hanzhou Wang, Jerry Chen, Milos Marinkovic, David D Dean, Xiao-Dong Chen, Adam B Salmon, Chih-Ko Yeh","doi":"10.14336/AD.2026.0057","DOIUrl":"https://doi.org/10.14336/AD.2026.0057","url":null,"abstract":"<p><p>The aging of salivary glands (SGs) leads to xerostomia, impaired oral defenses, and a compromised quality of life, yet the biology of human submandibular gland (SMG) aging remains poorly understood due to limited availability of human tissues and differences in anatomy and physiology between rodent and human SGs. The common marmoset (Callithrix jacchus) is a short-lived non-human primate (NHP) with SMG histology that closely resembles humans and has the potential to provide a translational model for investigating SG aging. In this study, we examined the age-associated structural and molecular alterations that occur in marmoset SMGs and evaluated whether chronic oral rapamycin treatment, a gerotherapeutic mTOR inhibitor, mitigates these age-related changes. Histological and immunofluorescence analyses revealed that there was a substantial decline in mucous and serous acinar units, expansion of ductal and collagen-rich stromal compartments, increased extracellular matrix remodeling, elevated dysregulation of lipid metabolism, and increased numbers of apoptotic and senescent cells in the SMG with aging. Rapamycin treatment was associated with partial preservation of acinar structure and a reduction in fibrosis, lipid accumulation, and number of apoptotic and senescent cells that resulted in an overall tissue phenotype that more closely resembled that of younger animals. These findings suggest that the aging marmoset SMG recapitulates key features of human SG aging and that rapamycin treatment was associated with an attenuation in the hallmarks of SG degeneration. The results suggest that the marmoset represents a valuable NHP model for studying SG aging biology and testing therapeutic strategies aimed at attenuating age-related structural degeneration associated with SG dysfunction.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350317","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Muscle-Brain Crosstalk in Alzheimer's Disease: Exercise-Associated FNDC5/Irisin Pathways in Preclinical Models - A Systematic Review.","authors":"Rafael Aguiar Marschner, Fernanda Marques da Silva, Daisy Crispim, Carlos Alberto Saraiva Gonçalves","doi":"10.14336/AD.2026.0427","DOIUrl":"https://doi.org/10.14336/AD.2026.0427","url":null,"abstract":"<p><p>Alzheimer's disease (AD) is a neurodegenerative disorder characterized by cognitive decline, synaptic dysfunction, neuroinflammation, and altered amyloid-β processing. Growing evidence suggests that physical exercise exerts neuroprotective effects partly mediated by myokines released from skeletal muscle. Among these, irisin, a cleavage product of fibronectin type III domain-containing protein 5 (FNDC5), has emerged as a potential component of muscle-brain communication involved in neuroplasticity and memory-related pathways. This systematic review summarizes evidence from preclinical in vivo studies investigating exercise-induced FNDC5 expression and irisin-related signaling pathways in experimental models of AD. A literature search was conducted in PubMed and EMBASE following PRISMA guidelines to identify studies evaluating the effects of physical exercise on FNDC5 expression, irisin-related pathways, and cognitive outcomes in animal models of AD. Ten preclinical studies met the inclusion criteria and were included in the qualitative synthesis, encompassing both behavioral and mechanistic evidence. Overall, the evidence indicates that physical exercise was associated with increased FNDC5 expression, activation of irisin-related pathways, and downstream neuroprotective mechanisms including PPARGC1A, AMPK, SIRT1, and BDNF signaling. These molecular adaptations were associated with improvements in synaptic plasticity, reductions in neuroinflammation and oxidative stress, and attenuation of amyloid-related pathology. Behavioral assessments across multiple paradigms also demonstrated improvements in learning and memory following exercise interventions. Collectively, the available preclinical evidence suggests that FNDC5/irisin-related signaling is associated with neuroprotective effects of physical exercise in experimental models of AD as part of a broader exercise-induced response. Further studies are needed to clarify the underlying mechanisms and translational relevance of this pathway in AD.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Extracellular Space Barrier Dysfunction Disrupts Interstitial Fluid Drainage and Is Associated with Memory Heterogeneity in Cognitive Aging.","authors":"Xin Mao, Rui Wang, Wanyi Fu, Hanbo Tan, Tianzi Gao, Dan Du, Yang Shi, Shufan Yang, Changming Wang, Yu Fu, Shaoyi Su, Meng Xu, Hongbin Han","doi":"10.14336/AD.2026.0422","DOIUrl":"https://doi.org/10.14336/AD.2026.0422","url":null,"abstract":"<p><p>Abnormal cognitive aging is characterized by memory decline beyond normal age-related physiological changes. Nevertheless, the intrinsic mechanisms driving individual memory heterogeneity during aging remain poorly elucidated. Given the critical roles of brain interstitial fluid (ISF) dynamics and extracellular space (ECS) transport in maintaining neural homeostasis, the present study aimed to explore whether ECS compartmentalization and ISF drainage disturbance contribute to interindividual variations in memory performance during aging. Aged rats were stratified according to their memory performance. A multi-modal strategy combining behavioral assessment, microdialysis, metabolomics, and electrophysiological recording was applied to detect structural and functional deficits in ECS barrier integrity and ISF drainage, with the assistance of MRI-based tracer imaging, fluorescence imaging, and ultrastructural observation. The results demonstrated that memory-impaired aged rats exhibited region-specific neurotransmitter imbalance in the caudate nucleus and thalamus, which was closely associated with age-related ECS barrier dysfunction. Such barrier dysfunction induced ISF drainage disturbance, thereby reducing local neurotransmitter concentrations in the caudate nucleus and impairing thalamocortical oscillations during non-rapid eye movement sleep, and ultimately disturbing memory consolidation. Further tracer imaging and electron microscopy examinations confirmed that compromised myelin integrity in the internal capsule served as the structural basis for age-related ISF drainage disturbance. Collectively, these findings reveal that ISF drainage disturbance induced by age-related ECS barrier alterations acts as a non-degenerative mechanism underlying memory heterogeneity in cognitive aging. This work highlights ECS compartment integrity as a promising biomarker and therapeutic target for intervening age-related cognitive decline.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":9.6,"publicationDate":"2026-06-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148350196","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating AI and Causal Genetics to Prioritize Therapeutic Targets for Aging and Age-Related Diseases.","authors":"Geoffrey H D Leung, Jianjiu Chen, I Aylin Ergun, Evgeny Izumchenko, Alex Aliper, Feng Ren, Frank W Pun, Alex Zhavoronkov","doi":"10.14336/AD.2026.0356","DOIUrl":"https://doi.org/10.14336/AD.2026.0356","url":null,"abstract":"<p><p>Aging is increasingly viewed as a pathological process and a principal driver of diverse age-related diseases (ARDs). Framing aging as a disease offers an opportunity to identify therapeutic targets capable of modifying multiple chronic disorders simultaneously. Here, we developed an artificial intelligence (AI)-driven target discovery framework that integrates large-scale multi-omic datasets to prioritize therapeutic targets shared between aging and 12 ARDs spanning four major disease areas: neurological, inflammatory, metabolic, and fibrotic disorders. We identified 29 high-confidence and 16 previously unrecognized aging-associated targets implicated across the selected disease areas, together with convergent pathway perturbations characterized by robust upregulation of interferon and inflammatory signaling, alongside coordinated downregulation of MYC-driven proliferative programs, consistent with heightened inflammatory activation and reduced anabolic activity during aging. Age-dependent transcriptomic alterations across tissues were observed for all identified target genes. Hallmarks of aging assessment revealed chronic inflammation as the most enriched hallmark across aging and ARDs. Mendelian randomization analyses provided genetic causal support for IL6, IL6R, NLRP3, NOS2, TLR4, and GLP1R in aging-related traits and multiple ARDs, highlighting potential opportunities for drug repurposing. Co-localization analyses suggested that the same genetic variants influencing IL6R expression are also associated with parental survival, a proxy for human lifespan, supporting a role for IL-6 signaling in longevity, and indicated a shared genetic signal at the NOS2 locus associated with rheumatoid arthritis risk. Together, our findings outline a scalable AI-guided multi-omic framework for identifying causal and repurposable therapeutic targets for aging and ARDs.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248780","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Peripheral Immune Challenge Drives Enteric α-Synuclein and Tau Pathology in LRRK2 G2019S Mice.","authors":"Carmela Giachino, Federico Bertoli, Cataldo Tirolo, Claudio Giuliano, Marika Mearelli, Meike Jakobi, Nicole Schneiderhan-Marra, Francesca L'Episcopo, Michela Deleidi","doi":"10.14336/AD.2026.0342","DOIUrl":"https://doi.org/10.14336/AD.2026.0342","url":null,"abstract":"<p><p>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by α-synuclein aggregation and dopaminergic neuron loss. Non-motor symptoms, including gastrointestinal dysfunction, often precede motor onset, suggesting a gut origin of pathology. LRRK2 variants increase susceptibility to both PD and Crohn's disease, pointing to a potential link between LRRK2 hyperactivity and early intestinal abnormalities; however, it remains unclear how LRRK2 contributes to enteric α-synuclein pathology and co-occurring proteinopathies. In this study, we investigated the interaction between chronic peripheral inflammation and the LRRK2 G2019S variant using a longitudinal mouse model combining ageing and repeated low-dose LPS exposure. We quantified peripheral cytokine levels, colonic immune cell infiltration (CD4⁺ T cells and macrophages), and the temporal progression of enteric α-synuclein and tau pathology across different ages. Our results showed that chronic LPS exposure induced an age-dependent increase in circulating cytokines and colonic immune infiltration in LRRK2 G2019S mice, accompanied by enhanced enteric α-synuclein accumulation and phosphorylation, alongside elevated tau phosphorylation, compared with wild-type controls. Notably, total neuronal counts remained stable, indicating a distinct pre-degenerative stage of pathology. Overall, our findings demonstrate that chronic peripheral inflammation synergizes with LRRK2 G2019S to trigger early intestinal inflammation and α-synuclein/tau co-pathology in the absence of overt neurodegeneration. These results suggest that LRRK2 acts as a critical link between systemic immunity and neuronal protein homeostasis, increasing the vulnerability of the gut to inflammatory stress. Characterizing this early pathological window provides key insights into PD initiation and highlights the gut as a promising target for early therapeutic intervention.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248730","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Biological Alignment Framework for Interpreting Anti-Inflammatory Cardiovascular Trials in Atherosclerosis.","authors":"Hua Yan, Dong Yi, Bingyin Wang","doi":"10.14336/AD.2026.10405","DOIUrl":"https://doi.org/10.14336/AD.2026.10405","url":null,"abstract":"<p><p>The inflammatory hypothesis of atherosclerosis has generated large-scale clinical trials with heterogeneous outcomes-from landmark success (CANTOS) to informative neutral results (CIRT). Understanding why anti-inflammatory therapies produce inconsistent outcomes requires a structured translational framework. We conducted a narrative review of randomized controlled trials, Mendelian randomization studies, and mechanistic investigations in anti-inflammatory cardiovascular therapy, searching PubMed, EMBASE, and the Cochrane database through December 2024. Trial outcomes were analyzed through four alignment domains: pathway specificity, target engagement, patient selection, and endpoint matching. Clinical trial outcomes can be systematically characterized by the degree of coherence-or biological alignment-across these four domains. High alignment (CANTOS, Total Alignment Score [TAS] 8/8) is associated with robust clinical benefit; partial alignment (COLCOT, LoDoCo2, TAS 6/8) yields consistent but modest effects; and low alignment (CIRT, TAS 4/8) is associated with neutral results. TAS is calculated as the additive sum of four domain scores (0-8); the \"multiplicative\" characterization in prior descriptions refers to a conceptual metaphor for rate-limiting failure, not a formal mathematical model. Aging-related processes (inflammaging, immunosenescence, clonal hematopoiesis of indeterminate potential [CHIP]) modify each alignment domain and require explicit incorporation into trial design. The Biological Alignment Model provides a mechanistically grounded, extensible framework for interpreting divergent anti-inflammatory cardiovascular trial outcomes. It enables iterative trial refinement and supports the design of precision immunotherapy strategies in atherosclerosis.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Community-Based Ocular Screening Integrated into Primary Healthcare for Older Adults: Design and 2-Year Follow-Up Results.","authors":"Gu Zheng, Shiqi Hu, Yiming Zhao, Yanyan Lin, Hairui Jiao, Wanwan He, Tianhao Huang, Shilei Wang, Cong Ye, Meixiao Shen, Ming Li, Jie Chen, Xinting Liu, Fan Lu","doi":"10.14336/AD.2026.10331","DOIUrl":"https://doi.org/10.14336/AD.2026.10331","url":null,"abstract":"<p><p>This research aims to describe the design, objective and feasibility of a pioneering community-based eye screening program intended to facilitate the provision of ocular services to the elderly. As a prospective investigation, this project innovatively integrates comprehensive eye examinations into routine annual physical assessments by leveraging cutting-edge automation, digital documentation, and real-time data transmission technologies. Eligible participants included community-dwelling adults aged ≥ 60 years undergoing health check-ups. Four foundational ophthalmic assessments, namely presenting distance visual acuity, autorefraction, intraocular pressure and non-mydriatic fundus photography, were measured to detect prevalent age-related eye diseases. Further, a dual-validation system combining artificial intelligence-driven analysis with on-site expert confirmation was implemented for high-risk case identification. Additionally, a tiered management strategy featuring rapid referral pathways was established to ensure timely tertiary care access. Among 3785 eligible residents, 3459 (91.4% response rate) completed initial screening, with an average examination duration of 4-8 minutes. Following expert validation, 1679 participants (48.5%) required advanced evaluation. Substantial unmet ophthalmic needs were uncovered, with prevalence rates of cataract (43.5%), age-related macular degeneration (37.5%), uncorrected refractive errors (14.6%), glaucoma suspicion (12.4%) and diabetic retinopathy (4.8%). A two-year follow-up analysis demonstrated observed visual improvements, particularly in younger cohorts (60-69 years). In contrast, the relatively older subgroup (70-74 years) exhibited progressive decline. This investigation establishes a model for geriatric vision care that demonstrated feasibility through its synergistic integration of technological innovation and existing primary community health infrastructure, although scalability to other populations and low referral completion require further evaluation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248670","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Spatiotemporal White Matter Pathology in Chronic Cerebral Hypoperfusion: Insights from the BCAS Mouse Model of Vascular Cognitive Impairment and Dementia.","authors":"Milton H Hamblin, Austin C Boese, Joseph Y Zhou, Tanvi Bobba, Jean-Pyo Lee","doi":"10.14336/AD.2026.0256","DOIUrl":"https://doi.org/10.14336/AD.2026.0256","url":null,"abstract":"<p><p>Vascular Cognitive Impairment and Dementia (VCID) comprises a heterogeneous group of cognitive disorders linked to cerebrovascular pathology and represents a major contributor to age-related cognitive decline worldwide. A hallmark pathological feature across VCID subtypes, including post-stroke dementia, subcortical ischemic vascular dementia, and mixed dementia, is chronic cerebral hypoperfusion, which is associated with progressive white matter (WM) degeneration. In preclinical research, sustained hypoperfusion is most commonly modeled using bilateral carotid artery stenosis (BCAS) in mice to investigate VCID mechanisms and therapeutic strategies. BCAS studies reveal that variables, including the severity of stenosis and the duration of hypoperfusion, critically influence the magnitude and temporal trajectory of WM pathology and cognitive dysfunction. Following BCAS, disease progression proceeds as a spatiotemporally ordered cascade of injury, characterized by early neuroinflammatory activation, blood-brain barrier dysfunction, progressive oligodendrocyte loss and demyelination, and subsequent cognitive decline. These pathological processes are modifiable through pharmacological, genetic, lifestyle, and neuromodulatory interventions that preserve WM integrity and cognitive function. The BCAS model is a critical platform for defining WM pathology, clarifying the temporal evolution of VCID, and advancing the development of therapeutic strategies targeting vascular contributions to cognitive aging.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vascular Aging Across the Cardiovascular-Alzheimer's Continuum: Hemodynamics and Artificial Intelligence.","authors":"Ziqiang Zhou, Ruihua Zhang, Jinwen Wang, Yajie Yu, Shepeng Wei, Weiqing Wan","doi":"10.14336/AD.2026.0539","DOIUrl":"https://doi.org/10.14336/AD.2026.0539","url":null,"abstract":"<p><p>Predicting health trajectories and accurately measuring aging processes across the human lifespan remain profound scientific challenges. Assessing the effectiveness and impact of interventions targeting aging is even more elusive, largely due to the intricate, multidimensional nature of aging-a process that defies simple quantification. Traditional biomarkers offer only partial perspectives, capturing limited aspects of the aging landscape. Yet, over the past decade, groundbreaking advancements have emerged. Epigenetic clocks, derived from DNA methylation patterns, have established themselves as powerful aging biomarkers, capable of estimating biological age and assessing aging rates across diverse tissues with remarkable precision. These clocks provide predictive insights into mortality and age-related disease risks, effectively distinguishing biological age from chronological age and illuminating enduring questions in gerontology. Despite significant progress in epigenetic clock development, substantial challenges remain, underscoring the need for continued investigation to fully unlock their potential in the science of aging.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248791","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Immersive Technologies of Virtual and Augmented Reality (VR/AR) in Patient-Centered Neurorehabilitation.","authors":"Fahad Somaa, Azka Khan, Mubin Mustafa Kiyani","doi":"10.14336/AD.2026.0360","DOIUrl":"https://doi.org/10.14336/AD.2026.0360","url":null,"abstract":"<p><p>Neurological disorders affect more than three billion individuals worldwide. Conventional neurorehabilitation is constrained by therapist dependency, limited treatment intensity, poor patient adherence, and restricted accessibility. VR/AR technologies offer immersive, high-dose, and remotely-deliverable alternatives to address these challenges. To synthesize current evidence on VR/AR applications in major neurological disorders; to evaluate alignment with patient-centered care principals, to assess relevant technological aspects and clinical outcomes, and to identify economic considerations, research gaps, and future directions. A narrative review was conducted using searches from large databanks, encompassing clinical trials, systematic reviews, and meta-analyses of VR/AR interventions in stroke, traumatic brain injury (TBI), spinal cord injury (SCI), Parkinson's diseases (PD), and multiple sclerosis (MS). Evidence was synthesized against a neurobiological and patient-centered care framework. VR and AR demonstrated clinically relevant potential across the neurological conditions examined. In stroke, VR added to conventional therapy produced moderate-certainty improvements in upper-limb motor recovery and balance. AR cueing significantly reduced freezing-of-gait duration and incidence in PD. VR interventions improved balance results in MS beyond those achieved with conventional therapy. In incomplete SCI, a large effect size on balance was reported, although with high heterogeneity. Some evidences support VR-based cognitive rehabilitation in TBI. Economic analysis indicated acceptable incremental cost-effectiveness and reimbursement pathways are emerging in several healthcare systems. VR/AR technologies are promising patient-centered tools in neurorehabilitation. Key gaps including absence of standardized reporting protocols, insufficient large multicentre trials, long-term data lacking from low-resource-settings. Addressing these gaps is essential for equitable, evidence-based global implementation.</p>","PeriodicalId":7434,"journal":{"name":"Aging and Disease","volume":" ","pages":""},"PeriodicalIF":6.9,"publicationDate":"2026-06-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148248683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}