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Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer's disease (AD). As a key neuronal resilience metabolite, the oxidized nicotinamide adenine dinucleotide (NAD^(+)) slows down AD progression in preclinical studies with several clinical trials ongoing. However, the underlying molecular mechanisms around how NAD^(+) enhances neuronal resilience, especially whether it has any effect on ASEs, have remained elusive. This study shows that NAD^(+) augmentation...

Evolutionary theory of aging predicts that women with increased reproductive effort live shorter lives, but evidence is inconsistent. These inconsistencies could be because environmental conditions influence how much a mother's life span is reduced when having more children, i.e., their life-span cost of reproduction. Using a structural equation measurement model, we compare how reproductive effort affects the life span of 4684 women exposed across different life stages, or not at all, to the...

Dysfunctional alternative splicing events (ASEs) in RNA are markers of aging and Alzheimer's disease (AD). As a key neuronal resilience metabolite, the oxidized nicotinamide adenine dinucleotide (NAD^(+)) slows down AD progression in preclinical studies with several clinical trials ongoing. However, the underlying molecular mechanisms around how NAD^(+) enhances neuronal resilience, especially whether it has any effect on ASEs, have remained elusive. This study shows that NAD^(+) augmentation...

Endocytic recycling of transmembrane proteins is essential to cellular function. The intracellular domains of transmembrane proteins are frequently ubiquitylated, a modification that is recognized by adaptor proteins during clathrin-mediated endocytosis. Recent work suggests that transmembrane proteins compete for space within highly crowded endocytic structures, suggesting that enhanced internalization of one group of transmembrane proteins may come at the expense of others. Here, we show that...

Advancing age is accompanied by an accumulation of senescent T cells that secrete pro-inflammatory senescence-associated secretory phenotype (SASP) molecules. Gut-microbiota-derived signals are increasingly recognised as immunomodulators. In the current study, we demonstrated that ageing and the accumulation of senescent T cells are accompanied by a reduction in microbial-derived short-chain fatty acids (SCFAs). Culturing aged T cells in the presence of butyrate suppresses the induction of a...

Renin-angiotensin system (RAS) activation in heart failure (HF) increases circulating angiotensin II (AII). This increases blood pressure (BP) and promotes adverse ventricular remodeling that makes HF worse. Although human HF increases with age and differs between the sexes, preclinical studies have used young, mostly male animals. We investigated sex differences in AII-induced cardiac remodeling in aging C57BL/6 mice. Mice (≈16 months) were infused with AII (3 mg/kg/day; 6 weeks; osmotic...

Muscle mass and strength influence various age-related health outcomes, however their individual and joint associations with biological aging remain understudied. This study investigated the associations of muscle health with epigenetic aging based on DNA methylation in blood samples, among middle-aged and older adults. We analyzed data from 1,121 individuals from the 1999-2002 cycles of the National Health and Nutrition Examination Survey. Muscle mass was assessed using the appendicular...

Stressful events can lead to transient impairments in learning and memory, a phenomenon more pronounced in the elderly. As global life expectancy rises, the shift toward an aging society underscores the urgent need for effective preventive strategies against stress-induced cognitive dysfunction. Elucidating its pathogenesis is essential for developing neuroprotective interventions and mitigating medical and societal impacts. In this study, male C57BL/6 mice aged 2 and 18 months were subjected to...

New effort is modeled after the state’s long-running cancer research institute

Mud-dwelling cable bacteria construct metal organic frameworks to grow

CONCLUSIONS: Elevated cumulative SBP, DBP, and PP independently increased subsequent cognitive impairment risk in Chinese older adults.

Genome-wide association studies (GWASs) have identified thousands of variants associated with neuropsychiatric disorders (NPDs), including autism spectrum disorder (ASD), schizophrenia (SCZ), and Alzheimer's disease (AD). However, deciphering the "causal" biological mechanisms and pathways through which these variants act remains a major obstacle that hinders translational understanding of NPD pathogenesis. NPDs are highly polygenic with contributions from pleiotropic variants across the allelic...