Aging & Longevity

Blood-brain barrier (BBB) dysfunction is an early feature of brain aging, but the endothelial mechanisms preserving barrier resilience remain unclear. Although we have reported α-synuclein (SNCA) supports vascular endothelial homeostasis, its role in the brain microvascular endothelium is unknown. Because SNCA loss suppresses eNOS/NO signaling and promotes endothelial β-site amyloid precursor protein cleaving enzyme 1 (BACE1) induction, we investigated whether senescence-associated SNCA decline...

CONCLUSION: Falls were associated with several demographic, socioeconomic, health-related, sensory, cognitive, and functional factors. These findings highlight the need for comprehensive fall-prevention strategies that address modifiable risk factors to reduce the burden of falls in aging populations.

CONCLUSIONS: Meaningful participation of older adults in DT for AI-driven assistive technology is methodologically and ethically important for producing acceptable, usable, and contextually appropriate technology. This evidence map offers guidance for geriatric researchers, clinicians, digital-health implementers, and policymakers committed to inclusive co-design with older adults, and identifies priority gaps for future primary research.

CONCLUSIONS: The results highlight the importance of health and social context in shaping life satisfaction in later life and suggest the need for integrated interventions supporting both physical and mental well-being among older adults.

Terrestrial ecosystems maintain a stable time-allocation budget between growth and senescence, but whether this applies to the ocean remains unclear. Using fused satellite LiDAR and ocean-color data (2007-2022), we show that marine phenology is variable and asymmetric. In high latitudes ( > 50°N), the bloom growth-to-decline ratio (R(GD)) is declining by ~5.3% per decade. While the chlorophyll-increase phase has lengthened by 2.3-5.5 days, the post-peak chlorophyll-decline phase has extended...

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, and cellular senescence serves as a core driving factor in the pathogenesis and progression of cardiovascular degeneration and related diseases. Sirtuins act as a crucial molecular hub linking cellular senescence to CVDs, and their upregulated activity is closely associated with delayed cellular senescence and preserved normal cardiovascular function; therefore, the research and development of small-molecule...

Aging leads to significant hair changes, including alopecia and graying, yet the underlying mechanisms remain unclear. Emerging evidence highlights the role of the extracellular microenvironment, particularly dermal white adipose tissue (dWAT), in regulating hair regeneration and pigmentation. Previous studies showed that young murine dWAT improves age-related hair phenotypes via follistatin upregulation. This study investigates key molecular mechanisms in dWAT governing hair aging, aiming to...

Adult hypothalamic neural stem and progenitor cells (htNSCs) influence aging partly through exosome-associated microRNA (miRNA) cargo, yet how their miRNA targetome relates to hypothalamic aging remains unclear. We mapped htNSC-biased miRNAs onto miRTarBase to define a 1777-gene target union and tested whether gene-level target burden aligns with public hypothalamic aging transcriptomes. The primary Spearman correlation between miRTarBase-weighted burden and GSE188646 aging log fold-change is...

CONCLUSION: The combination of low PEF and high cardiometabolic burden identified an older subgroup at elevated risk of incident ADL disability. However, the small and heterogeneous multiplicative interaction and near-null additive interaction estimates did not support a consistent interaction beyond the separate associations.

CONCLUSIONS: This multi-database explainable machine learning analysis reveals robust cross-sectional predictive associations between frailty and concurrent depression among older adults with multimorbidity. The predictive models facilitate clinical risk stratification for the concurrent screening of high-risk individuals for both conditions. However, the present cross-sectional design prohibits confirmation of temporal ordering and causal reciprocal reinforcement. The findings highlight the...

CONCLUSIONS: Physical performance assessed by the SPPB was significantly associated with dementia risk. These findings support the potential value of the SPPB in identifying older adults at higher risk of dementia. Future intervention studies are needed to determine whether improving physical performance can reduce dementia risk.

CONCLUSION: L1 expression increased in the aged mouse PFC and is associated with coordinated downregulation of neuronal gene networks rather than other major aging-associated transcriptional programs. These findings further characterize the molecular context of increased L1 expression during normal brain aging.

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Aging is the dominant risk factor for retinal neurodegeneration, yet the upstream regulators that coordinate senescence-associated programs across retinal cell types remain incompletely defined. Here we combined bulk RNA-seq and quantitative proteomics of retinas from naturally aged (24-month) and young (4-month) mice to define age-associated molecular programs and infer upstream regulators. We identified coordinated but imperfect transcript-protein coupling, with prominent immune and metabolic...

A progressive decline in testosterone levels is a hallmark of male reproductive aging and is closely associated with impaired Leydig cell function. Leydig cell function relies on intracellular homeostasis, with endoplasmic reticulum (ER) homeostasis playing a particularly important role in steroidogenesis. The ER supports steroidogenesis by regulating protein quality control, lipid and cholesterol metabolism, calcium homeostasis, and interactions between organelles. With advancing age, the...

How diet shapes aging and age-related diseases marked by senescent cell accumulation remains unclear. Here we report vanadyl sulfate (VS), a mineral dietary supplement, as a senolytic agent. Oral VS ameliorates phenotypes of aging and diverse age-related disorders and extends lifespan in male mice. Integrated functional omics analyses show that senescent cells exhibit globally reduced proteome cysteine reactivity but increased expression and apparent cysteine reactivity of proteins essential for...

Torque teno viruses (TTVs) are ubiquitous components of the human virome whose replication is tightly regulated by host immunity. While elevated total TTV load has been associated with increased mortality in older adults, the clinical relevance of species-level virome composition remains unclear. We profiled the circulating anellovirome in 251 hospitalized older adults using amplicon-based whole-genome sequencing and investigated associations with frailty, cognitive impairment, mortality, immune...

Multiple object tracking (MOT) is a core function of dynamic visual attention that relies on the ability to simultaneously monitor several moving objects. Although MOT performance is known to decline with age, and to depend on efficient oculomotor strategies, how these processes interact across the adult lifespan and under degraded visual input remains poorly understood. Here, we examined age-related differences in MOT under normal and gaze-contingent viewing conditions simulating central and...

We characterize the spatiotemporal dynamics of the tumor microenvironment (TME) in bladder cancer (BLCA) samples before and after neoadjuvant immunotherapy in a multicenter real-world cohort (n = 606). We identify two distinct differentiation outcomes in BLCA epithelial cells: sensitivity and resistance to immunotherapy. Additionally, we identify SERPINH1 as a common target of acquired immunotherapy resistance in BLCA. Furthermore, we characterize an immunotherapy-induced tumor-myeloid barrier,...

T cell senescence is an important dysfunctional state associated with tumor progression, but whether senescent T (Tsen) cells directly reprogram tumor cell behavior remains unknown. Here, single-cell transcriptomic analyses identify abundant Tsen cells across breast, colorectal, and lung cancers. Tsen cells actively promote tumor growth, metastasis, stemness, and chemotherapy resistance by reprogramming tumor cells in vitro and in vivo. Mechanistically, lipid-enriched senescence-associated...