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Saliva is an accessible biofluid with potential for non-invasive disease diagnostics. This study explores how genetic susceptibility to common diseases is reflected in DNA methylation (DNAm) and gene expression profiles in saliva. We constructed cis-mQTL (n = 345) and cis-eQTL (n = 277) datasets and examined correlations between DNAm and gene expression. Saliva QTLs were integrated with summary statistics from 36 genome-wide association studies (GWAS) using Summary-based Mendelian Randomization...

Influenza A virus (IAV) infection causes acute and long-term lung damage. Here, we used immunostaining, genetic, and pharmacological approaches to determine whether IAV-induced cellular senescence causes prolonged alterations in lungs. Mice infected with a sublethal dose of H1N1p2009 exhibited cellular senescence, as evidenced by increased pulmonary expression of p16, p21, β-galactosidase and the DNA damage marker gamma-H2A.X. Cellular senescence began 4 days post-infection (dpi) in the...

Tobacco use is the main source of indoor air pollution and contains a variety of toxic components. The smoke from burning cigarettes is a key environmental risk factor that leads to accelerated aging and the occurrence of numerous diseases. Meanwhile, cigarette smoke and aging are both prominent risk factors for age-related macular degeneration (AMD). This study demonstrates that long-term exposure to cigarette smoke can impair retinal function and induce the aging of retinal pigment epithelium...

Cochlear aging causes substantial hearing impairment in older adults, yet primate-specific mechanisms remain poorly characterized. Our comprehensive analysis combining single-cell and histopathological profiling in aging Macaca fascicularis demonstrates progressive cochlear degeneration featuring accelerated sensory hair cell loss, senescent spiral ganglion neurons with elevated neuroinflammation, and marked stria vascularis atrophy. We discovered that downregulation of transmembrane transport...

Excessive exposure of the skin to UV radiaton (UVR) accelerates the aging process and leads to a photoaging state which involves similar pathological alterations to those occurring in chronological aging. UVR exposure, containing both UVA and UVB radiation, triggers cellular senescence and a chronic inflammatory state in skin. UVR promotes oxidative stress and a leakage of double-stranded DNA (dsDNA) from nuclei and mitochondria into the cytoplasm of keratinocytes and fibroblasts. It is...

Cortical tau deposition begins in higher-order association regions and spreads to lower-order primary sensory-motor networks in moderate/advanced Alzheimer's dementia. The neural mechanisms underlying this spatiotemporal pattern remain elusive. Initial evidence has shown that coupled dynamic, low-frequency (<0.1 Hz) brain activity in cerebrospinal fluid (CSF) flow and gray matter (global brain-CSF coupling) might be related to CSF clearance and thus β-amyloid accumulation. Here, we report that...

Previous studies have shown that dietary selenium (Se) deficiency in mice reshapes gut microbiota, exacerbates healthspan deterioration (e.g., type 2 diabetes), and paradoxically activates beneficial longevity pathways. This study demonstrated that dietary Se deficiency accelerated many age-related gut microbial changes in aged telomere-humanized C57BL/6J diabetic mice in a sexually dimorphic manner, with Akkermansia muciniphila showing the greatest enrichment in males. However, dietary Se...

T stem cell-like memory cells (TSCM cells) are considered to be essential for the maintenance of immune memory. The TSCM population has been shown to have the key properties of a stem cell population: multipotency, self-renewal and clonal longevity. Here we show that no single population has all these stem cell properties, instead the properties are distributed. We show that the human TSCM population consists of two distinct cell subpopulations which can be distinguished by the level of their...

Cellular senescence is an aging-related mechanism characterized by cell cycle arrest, macromolecular alterations, and a senescence-associated secretory phenotype (SASP). Recent preclinical trials established that senolytic drugs, which target survival mechanisms of senescent cells, can effectively intervene in age-related pathologies. In contrast, senomorphic agents inhibiting SASP expression while preserving the survival of senescent cells have received relatively less attention, with potential...

Age is a significant risk factor for functional decline and disease of the musculoskeletal system, yet few biomarkers exist to facilitate ageing research in musculoskeletal tissues. Multivariate models based on DNA methylation, termed epigenetic clocks, have shown promise as markers of biological age. However, the accuracy of existing epigenetic clocks in musculoskeletal tissues are no more, and often less accurate than a randomly sampled baseline model. We developed a highly accurate epigenetic...

OBJECTIVES: Self-relevant stimuli, such as one’s name or face, are prioritised by the brain, leading to faster responses and enhanced attentional processes. The psychophysiological underpinnings of those mechanisms are related to early and late event-related potential (ERP) components, particularly to reduced N2 and enhanced late positive potential (LPP). However, most up-to-date research on the self has focused on groups of young adults while older groups were rarely recruited for such...

This study offers the first in-depth analysis of the Village Movement since its launch in 2002, examining the socioeconomic and institutional factors behind the growth and sustainability of Villages, community-based organizations that support aging in place. Using a mixed-methods approach, the research combines survey data, case studies, interviews, field observations, and regression analysis. Findings show that Villages are grassroots' responses to the breakdown of traditional social networks...

Aging is the greatest risk factor for learning and memory disorders; dementia prevalence significantly increases with age due to numerous molecular changes in the body. Although research has consistently shown that aging leads to learning and memory impairments, the molecular mechanisms linking aging to these cognitive deficits remain incompletely understood. Previous studies have revealed that complement C3 levels increase with age in humans, monkeys, and mice; elevated C3 expression is also...

This study investigates the impact of dietary restriction (DR) on gene expression in hematopoietic stem cells (HSCs) derived from aged mice. RNA sequencing (RNA-seq) data were obtained from sorted HSCs, followed by weighted gene co-expression network analysis (WGCNA) to identify differentially expressed genes (DEGs) and key transcriptional modules. Principal component analysis (PCA) and heatmaps revealed significant differences between the groups, highlighting a predominant upregulation of gene...

Few studies have comprehensively measured the changes in cognition occurring in the years before and after the onset of specific respiratory disease type, which could help tailor the timing and design of future intervention strategies. Here we aimed to explore the temporal pattern of cognitive change before and after incident COPD and asthma. Data from wave 1 to wave 9 (2002-2018) of the English Longitudinal Study of Ageing were used. Global cognition, assessed by orientation, memory, and...

Developing lenacapavir, the drug newly approved to protect against HIV for six months in one shot, took basic science, sophisticated chemistry, and perseverance