Aging & Longevity

The antagonistic pleiotropy theory of aging predicts genetic trade-offs between early-life and late-life fitness. However, empirical evidence for such trade-offs in vertebrates remains scarce, particularly from causal genetic experiments. Here, combining genetic perturbation with longitudinal phenotyping in the turquoise killifish (Nothobranchius furzeri), we identify vestigial-like 3 (vgll3), previously linked by GWAS to age at maturity in humans and male Atlantic salmon, as a gene with...

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Excessive artificial light at night (ALAN) disrupts circadian rhythms and may accelerate ocular aging; however, personal objective dosimetry data linking evening light exposure to specific age-related eye diseases (AREDs) remain sparse. The objective of the study is to determine whether personal high-intensity light exposure during the evening transition window (20:00-23:30) is associated with the risk of incident age-related macular degeneration (AMD), cataracts, and glaucoma. This prospective...

Time-restricted feeding (TRF) aligned with an organism's circadian rhythm has been shown to improve health, but its long-term effects on healthspan and lifespan in mammals, especially under standard dietary conditions that do not promote obesity, remain unclear. Here, we examined the impact of 12-h and 8-h nightly TRF windows in 264 male and 264 female C57BL/6 J mice fed regular chow. TRF improved multiple health measures, including behavioral rhythmicity, body weight and composition, frailty,...

The DREAM complex has emerged as a central repressor of DNA repair, raising questions as to whether such repression exerts long-term effects on human health. Here we establish that DREAM-associated activity significantly impacts lifetime somatic mutation burden, and that such effects are linked to altered lifespan and age-related disease pathology. First, joint profiling of DREAM-associated activity (quantified from the expression of genes transcriptionally repressed by DREAM) and somatic...

Glucagon-like peptide-1 receptor agonists, including long-acting semaglutide, are transformative anti-obesity therapies. However, emerging evidence indicates that weight loss may come at the expense of skeletal muscle mass, a tissue essential for mobility, metabolic regulation, and overall health. Here, we show that inhibition of the gerozyme 15-hydroxyprostaglandin dehydrogenase (15-PGDH), a prostaglandin-degrading enzyme that increases with injury and aging, improves muscle repair and strength...

Trade-offs between lifespan and reproduction are a central theme in evolution and ecology, often attributed to physiological constraints on the allocation of limiting resources. However, recent work suggests such trade-offs may depend on macro- and micronutritional context. We examined how macronutrient balance and cholesterol availability shape lifespan and reproductive performance in male Drosophila melanogaster, explicitly testing both unmated males and those permitted to mate freely...

Ovarian cancer is characterized by a high recurrence rate, and platinum resistance often contributes to poor patient outcomes. Cellular senescence can influence the tumor microenvironment, metabolic status, and immune regulation. However, the role of senescence-associated genes (SAGs) in the heterogeneity, prognosis, and treatment-related features of ovarian cancer remains to be further clarified. This study integrated data from TCGA, GEO, and single-cell RNA sequencing to systematically analyze...

Systemic microbial infection leading to septic shock with multiple organ dysfunction syndrome (MODS) is a major cause of mortality and represents a substantial unmet medical need. We recently observed that, compared with uninfected controls, patients with septic shock exhibit significantly elevated circulating concentrations of the tissue hormone acyl-CoA binding protein (ACBP), encoded by the diazepam binding inhibitor (DBI) gene, a potent inhibitor of autophagy. Increased plasma DBI/ACBP...

Benign prostatic hyperplasia (BPH), prevalently in aging men, is characterized by aberrant cell death of prostate cells. Anoikis, a specific subtype of apoptosis, is triggered when cells detach from the extracellular matrix (ECM), in contrast, cells with anoikis resistance contribute to pathological processes such as unregulated cell proliferation and impaired cell death. However, the role of anoikis resistance in BPH pathogenesis remains poorly understood. In this study, an elevated anoikis...

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Anxiety disorders are prevalent and can greatly impact well-being. The biological mechanisms behind anxiety are not fully understood, but growing evidence suggests a role for DNA methylation. Here, we conduct a large-scale methylome-wide association study of lifetime anxiety in 14,443 participants (1817 cases and 12,626 controls) in whole blood, and, through epigenomic deconvolution, 12 different blood cell types. We detect four CpG associations at methylome-wide significance in whole blood, and...

In Italy, evergreen holm oaks (Quercus ilex) and deciduous sessile oaks (Quercus petraea) experienced a synchronized establishment pulse starting at the beginning of 1400s CE, consistent with a release from anthropogenic pressure following demographic collapse associated with the Black Death outbreak (1347 CE) and its following waves until the 17th century. Radiocarbon dating of the oldest-looking individuals of each species revealed similar tree-age distributions across sites located at the...

Bilingualism has been associated with enhanced executive functions (EFs), particularly attentional control, and may confer protection against cognitive decline in older age. At the same time, the COVID-19 pandemic has emerged as a factor negatively affecting EF in older adults. Bilingualism might offer resilience against these COVID-related cognitive declines, especially in late adulthood, by bolstering cognitive reserve. The present study collected data from 312 community-dwelling individuals...

Cohesin is a DNA tethering complex essential for chromosome structure and function. In fission yeast, defects in the cohesin loader Mis4 result in chromosome segregation defects and dysregulated expression of genes near chromosome ends. A genetic screen for suppressors of the thermosensitive growth defect of mis4-G1487D identified several hypomorphic mutants of the Target of Rapamycin Complex 1 (TORC1), a conserved kinase that integrates cellular signals to regulate growth and metabolism through...

Multimorbidity, the presence of two or more conditions, is associated with a higher risk of death as individuals age. However, modeling multimorbidity in laboratory animals is difficult, if not impossible, because specific conditions are seldom individually diagnosed and treated in these settings. Because of their shared environment, physiology, and genetic diversity, and because they are medically managed as individuals, companion dogs have potential to serve as a translational multimorbidity...

Biological aging is a key determinant of liver disease and mortality, but there is little evidence on noninvasive index for assessment of liver biological aging. We developed the Liver Aging Index (LAI) in the China Kadoorie Biobank (CKB, N = 21,629) using Cox-Gompertz proportional hazards model. The LAI incorporated three clinical factors (body mass index, systolic and diastolic blood pressure), eight plasma biomarkers (glucose, total cholesterol, triglycerides, high- and low-density...

Long Interspersed Element-1 (L1) causes DNA damage and inflammation, which are hallmarks of cellular senescence. To understand the role of endogenous L1 in senescence, accurate detection and measurement of L1 messenger RNA (mRNA) expression changes during this process is crucial, as L1 transcription is the prerequisite step of L1-related downstream effects. We developed an automated bioinformatics pipeline to quantify locus-level L1 mRNA expression in ex vivo and in vitro models of normal and...

This study tests the moderating role of essentialist beliefs about aging (i.e., perceptions of aging as a fixed versus malleable process) in the relationship between physical functioning and subjective well-being distinguishing between a) overall quality of life and b) health satisfaction among older adults in clinical care. We propose that essentialist beliefs serve as adaptive, palliative cognitions that help maintain high subjective well-being despite health challenges. In a sample of...