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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...

Accurately predicting disease progression remains a major challenge in Alzheimer's disease (AD). Here we show that a biomarker-integrated prognostic staging system can stratify progression risk across the disease course by jointly incorporating cognitive status, established risk factors, plasma biomarkers, and neuroimaging measures. In the K-ROAD cohort (N = 1,263), the dominant prognostic contributors varied by clinical context-GFAP in cognitively unimpaired individuals, hippocampal volume 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...

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...

Selective neuronal vulnerability is a hallmark of Alzheimer's disease (AD), yet the molecular basis of resilience remains poorly understood. Using single-nucleus and spatial transcriptomics to compare neocortical regions affected early (prefrontal cortex, precuneus) or late (primary visual cortex) in AD, we identified a resilient excitatory population in layer 4 of the primary visual cortex expressing RORB, CUX2, and EYA4. Layer 4 neurons in association neocortex shared molecular signatures of...

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...