Aging & Longevity

Detecting heterogeneity in treatment response enriches the interpretation of gerontologic trials. In aging research, estimating the intervention's effect on clinically meaningful outcomes poses analytical challenges when outcomes are truncated by death. For example, in the Whole Systems Demonstrator trial, a large cluster-randomized study evaluating telecare among older adults, the overall effect of the intervention on quality of life was found to be null. However, this marginal intervention...

CONCLUSIONS AND IMPLICATIONS: In a frail older outpatient population, SCORE2-OP showed notable discrimination for CVD mortality in those without ASCVD history. This suggests that SCORE2-OP can be used for CVD risk estimation in these frail outpatients.

Fuchs endothelial corneal dystrophy (FECD) is an age-related disorder characterized by excessive extracellular matrix (ECM) deposition and loss of corneal endothelial cells (CEnCs), eventually leading to corneal blindness. Despite known environmental and genetic contributors, the roles of aging and hormonal influences, particularly in the predominantly female population, remain underexplored in FECD. This study investigates the impact of chronic exposure to combined ultra-violet (UV-A) light and...

Cells contain membrane-bound and membraneless organelles that operate as spatially distinct biochemical niches. However, these reaction centers lose fidelity due to aging or diseases. A grand challenge for biomedicine is restoring or augmenting cellular functionalities. An excited strategy is the delivery of protein-based materials that can directly interact with cellular biological networks. In this study, we sought to develop long-lasting materials capable of cellular uptake, akin to...

Aging is accompanied by low-grade intestinal inflammation, shifts in gut microbiota, and impaired oxidative balance. Probiotic supplementation has been proposed to mitigate these processes, yet evidence in elderly populations remains limited. In this pilot trial, older adults received oral Lactiplantibacillus plantarum OL3246 or placebo, with assessments including fecal calprotectin and zonulin as markers of intestinal inflammation, systemic oxidative stress parameters, self-reported quality of...

The endoplasmic reticulum (ER) comprises an array of subdomains, each defined by a characteristic structure and function. Although altered ER processes are linked to age-onset pathogenesis, it is unclear whether shifts in ER structure or dynamics underlie these functional changes. Here we establish ER structural and functional remodelling as a conserved feature of ageing across yeast, Caenorhabditis elegans and mammals. Focusing on C. elegans as the exemplar of metazoan ageing, we reveal...

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CONCLUSION: In summary, anodal, but not cathodal, so-tDCS effectively enhanced thalamocortical interactions underlying memory consolidation. Furthermore, these findings highlight the importance of individual factors such as chronotype in brain stimulation responsiveness.

Alzheimer's disease (AD) is characterized by the accumulation of misfolded proteins that trigger neuroinflammation and neuronal loss. The retina, as an extension of the central nervous system, mirrors these pathological processes and represents a potential biomarker. Microglial activation, a key component of neuroinflammation, can be morphologically assessed through automated image analysis. This study performed a quantitative and morphological analysis of retinal microglia in the...

CONCLUSION: Increased expression of p16 and p21 in ascending aortic tissue is significantly associated with higher coronary atherosclerosis complexity in patients undergoing CABG. Among these biomarkers, p16 serves as an independent predictor of complex CAD, highlighting its potential role in vascular aging and atherosclerosis progression.

Aging impacts immune function, but the mechanisms driving age-related changes in immune cell subsets remain unclear. To explore age-dependent changes in immune cell populations, we analyzed human peripheral blood mononuclear cells (PBMCs) from a cohort of healthy donors aged 20-82 years using a 36-color spectral flow cytometry panel focused on T cells. We identified a unique population of memory CD8 T cells, which lack CXCR3 and produce a Th2-like cytokine response, and accumulate with age. We...

Aging is the primary risk factor for numerous chronic diseases, making the identification of safe and effective anti-aging strategies a critical focus in biomedical research. Heterochronic parabiosis by blood exchange shows that the exchange interaction between young and old plasma can exert anti-aging effects through exchange of bloodborne factors. However, the limited plasma source greatly affects clinical translation. Here, we demonstrate that periodic therapeutic phlebotomy in...

Epigenetic alterations are an important shared hallmark of ageing and cancer. The development of epigenetic markers of ageing using blood DNA methylation data has been an active area of research. These markers have been used to assess disease risk, with potential to shed light on the complex link between ageing and cancer. We comprehensively summarised the literature on the most widely used and recently developed epigenetic markers of ageing, and synthesised the findings from studies that...

CONCLUSIONS: The findings suggest that ADS may function as a complement to-rather than a substitute for-informal care and is associated with reduced institutionalization risk. Optimizing ADS delivery to match caregiving capacity may further enhance effectiveness.

The meninges, long viewed as passive protective membranes, are now recognized as active immunological interfaces harboring diverse immune populations. Among them, B cells have emerged as dynamic participants in central nervous system (CNS) homeostasis and disorders. Recent studies have identified distinct B cell subsets in the meninges at different developmental and activation stages, including precursors supported by skull marrow-derived progenitors and immunoglobulin A (IgA)⁺ plasma cells...

The immune system could play an important role in the age-related decline in brain function, yet specific immune-based strategies to enhance brain resilience in older individuals are lacking. Here, we combined engineered proteins and direct brain delivery to target immune cell populations within the old brain. We detected T cells with an exhaustion signature in the old brain and targeted them with a potent engineered checkpoint inhibitor (RIPR-PD1). This led to T cell expansion and strong...

The nasal microbiome has emerged as a previously underrecognized modulator of neuroinflammation and central nervous system (CNS) homeostasis. Beyond its role in respiratory host defense, this microbial niche is anatomically positioned to directly influence brain physiology through olfactory neuronal pathways, systemic immune signaling, and inter-organ communication within the gut-lung-brain axis. Accumulating evidence indicates that nasal microbiome dysbiosis contributes to blood-brain barrier...

CONCLUSION: This study indicates that educational attainment, frequency of physical activity, oral health status, and metabolic factors are associated with temporal variation in the risk of cognitive impairment among older adults. Focusing on these modifiable factors may inform feasible, actionable screening and prevention strategies in primary care and community settings. Our findings also underscore the importance of dynamic monitoring of these indicators and suggest their potential value in...

CONCLUSIONS: Recommendations to improve dementia care planning and post-diagnostic support for South Asian communities include (1) Reframing narratives around dementia and help-seeking through culturally-tailored community interventions; (2) Culturally competent, person- and family-centred care; (3) Holistic and integrated support beyond clinical care; (4) Equitable partnership working with South Asian communities to co-produce dementia services.