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The mitochondrial unfolded protein response in human microglia disrupts neuronal-glial communication and promotes senescence

2 weeks 4 days ago
Mitochondria have evolved a specialized mitochondrial unfolded protein response (UPR^(mt)) to maintain proteostasis and promote recovery under stress. Studies in simple organisms have shown that UPR^(mt) activation in glial cells supports proteostasis through beneficial non-cell-autonomous communication with neurons. However, the role of mitochondrial stress responses in the human brain remains unclear. To address this gap, we investigated the cell-type-specific effects of mitochondrial...
Maria Jose Perez J

Network-driven discovery of repurposable drugs targeting hallmarks of aging

2 weeks 4 days ago
Despite the thousands of genes implicated in age-related phenotypes, effective interventions for aging remain elusive, due to the multifactorial nature of longevity and the interconnectedness of molecular components involved. Here we introduce a network medicine framework to map 2,358 longevity-associated genes onto the human interactome to identify drug-repurposing candidates capable of modulating specific hallmarks of aging. We find that genes associated with each hallmark form a connected...
Bnaya Gross

Meta-analysis of DNA methylation aging signatures in 17 human tissues

2 weeks 4 days ago
Epigenetic changes, in particular DNA methylation, accumulate with age across different tissues, but whether these changes follow consistent patterns across different organs remains poorly understood. Here we show, through a meta-analysis of more than 15,000 human methylation profiles spanning 17 tissues, that aging produces both conserved and tissue-specific epigenetic signatures. We identify systemic shifts in methylation levels, increases in methylation variability, and growing molecular...
Macsue Jacques