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Valvular heart disease (VHD) is a highly prevalent age-associated cardiovascular pathology. VHD can be characterised by stenosis, an increase in valve stiffening commonly due to leaflet calcification, or regurgitation, where backflow of blood can occur as a result of valve remodelling. At present, there is a paucity of spontaneous animal models of valve disease which would aid mechanistic investigations and allow therapeutic screening. Here, we report a spontaneously occurring zebrafish valve...

A decrease in osteoblast number and bone formation are seminal contributors to age-related osteoporosis. However, the aging-associated molecular mechanisms that impact osteoblast precursors, osteoblasts, osteocytes, and other bone mesenchymal cell types remain unclear. We performed single-cell RNA-sequencing of mesenchymal cells present at the endosteum and periosteum of young and old C57BL/6 mice of both sexes. Osteoblast precursors and osteoblasts from female endosteum exhibited the greatest...

Many studies have compared gene expression in young and old samples to gain insights on aging, the primary risk factor for most chronic diseases. However, these studies only identify associations without distinguishing drivers of aging from compensatory geroprotective responses or incidental downstream effects. Here, we introduce a workflow to characterize causal effects of differentially expressed genes on lifespan. First, we performed a meta-analysis of 25 gene expression datasets comprising...

Autophagy is intricately linked with protective cellular processes, including mitochondrial function, proteostasis, and cellular senescence. Animal studies have indicated that autophagy becomes dysfunctional with aging and may contribute to T cell immunosenescence. In humans, it remains unclear whether autophagy is impaired in CD4^(+) T cells as people age. To answer this question, we examined basal and inducible autophagic activity in a series of experiments comparing CD4^(+) T cells from...

Immune cell metabolism is increasingly recognized as an important regulator of immune function, but its role in age-related immune dysfunction, chronic inflammation, and cardiometabolic complications in humans remains incompletely understood. This study investigated the impact of aging on monocyte metabolic and functional signatures in a healthy elderly population. We aimed to leverage these immunometabolic signatures to identify healthy elderly individuals with reduced immune cell fitness and,...

Museum specimens collected during a 1907 marine expedition reveal loss of genetic diversity in the Philippines

Joel Mokyr, Philippe Aghion, and Peter Howitt explained why the past 2 centuries have seen sustained economic growth rather than stagnation

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