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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...

Drinking two to three cups of caffeinated coffee daily was linked to a dramatically lower risk of dementia and better cognitive functioning in a study spanning up to 43 years. The benefits appeared regardless of genetic risk, but decaffeinated coffee did not show the same association.

A surprising discovery reveals how psilocybin, the active compound in magic mushrooms, rapidly reshapes the brain by creating new neural connections and strengthening them. Researchers found that the drug behaves differently in healthy and chronically stressed mice, potentially helping repair brain circuits damaged by prolonged stress. Most intriguingly, they identified a way to trigger this brain rewiring without the behavioral response associated with psychedelic effects.

A compound naturally found in broccoli could help fight Friedreich ataxia, a devastating genetic disease that progressively damages the nervous system, by boosting a vital protein and protecting nerve cells. Scientists hope the discovery could lead to an affordable treatment, although clinical trials are still needed to establish its effectiveness in patients.

Approach could provide scientists with a quicker, gentler way to gauge the health of bird populations

Representative Zoe Lofgren prepares to lead the House science committee that microbiologist Jasmine Clark hopes to serve on

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Alzheimer disease (AD) is defined neuropathologically by the presence of amyloid plaques and neurofibrillary tangles, yet these canonical lesions alone cannot account for its clinical, regional and cellular heterogeneity. AD is a multicellular, spatially organized disease shaped by the interactions of neurons, glia and vascular cells within distinct anatomical microenvironments. Single-cell and single-nucleus RNA sequencing have made it possible to dissect the transcriptional signatures of...

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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,...