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CONCLUSIONS: Our survey results indicate that older adults preferred to seek and receive HHC through traditional medical settings. These data were collected prior to the pandemic and before some of the recent OTC policy changes; nonetheless, they align with more recent findings and capture the attitudes of individuals who are likely still making HHC decisions today. These findings, therefore, provide contextual evidence about older adults' reported preferences against which future studies of...

Testosterone levels decline progressively with age from the third decade of life, impairing spermatogenesis and contributing to age-related disorders, underscoring the importance of enhancing endogenous testosterone production. DNA methyltransferase 1 (DNMT1) promotes testosterone synthesis in Leydig cells (LCs), yet the underlying mechanism remains unclear. Here, we found that DNMT1 expression is downregulated in aging rat testes and senescent LCs in vitro, correlating with reduced testosterone...

Although Alzheimer's disease (AD) has a polygenic architecture, with numerous associated single-nucleotide polymorphisms (SNPs) identified, the contribution of structural variants (SVs) is unclear. In this study, using long-read (n = 11) and short-read (n = 3,190) sequencing data from the Chinese population, we show that common SVs contribute to AD heritability beyond common SNPs. We identify an expanded CCG repeat in the FAM193B promoter that shows a genome-wide significant association with...

DNA methylation (DNAm) plays a critical role in Alzheimer's disease (AD). Previous epigenome-wide association studies using 450K arrays captured limited CpG coverage and often focused on a single neuropathological measure. Here we profiled DNAm in 1,250 postmortem prefrontal cortex samples from the Rush Alzheimer's Disease cohorts using the Infinium MethylationEPIC v2 array (~930,000 CpGs) and performed epigenome-wide association studies of multiple neuropathologic measures, including AD...

Cognitive impairment affects 30%-80% of patients with heart failure, yet the mechanisms beyond reduced brain blood flow remain poorly defined. Here we show that circulating factors released during heart failure trigger senescence of brain blood-vessel endothelial cells, which in turn drives synaptic loss and cognitive decline through crosstalk between endothelial cells and microglia, the brain's immune cells. Using a pressure-overload model (transverse aortic constriction) combined with plasma...

Chronic social deficits (persistent feelings of being lonely or isolated) have been linked to premature mortality, yet the underlying physical and mental pathways remain unclear. This study used data from 4,090 older adults in the English Longitudinal Study of Ageing, a longitudinal panel study. Using outcome-wide analyses, we assessed how the chronicity of social deficits was associated with 17 health outcomes across physical, mental, cognitive and behavioural health domains. Regression models...

The buried interface between the charge transport layer and the overlying perovskite absorber is critical yet difficult to probe in perovskite solar cells. Because light enters through the transparent substrate and is predominantly absorbed near this region, photo-induced degradation processes are partially initiated at the hidden buried interface. Here, we reveal that instability at the buried SnO(2)/perovskite interface triggers structural and chemical decomposition of the perovskite layer. To...

Alzheimer's disease (AD) disproportionately affects women, yet mechanisms underlying this sex difference remain unclear. Histone variants are overrepresented components of aging neuronal chromatin, but their contribution to AD is unknown. Here, we identify the histone variant H2A.Z as a sex-specific regulator of AD in the postmortem human hippocampus and in 5xFAD mice. H2A.Z occupancy decreased in female but increased in male AD patients. In females, reduced H2A.Z occupancy at the transcription...