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Gene expression changes in cord blood-derived ECFCs in response to in vitro senescence stimuli

ABSTRACT: Senescent endothelial cells accumulate in blood vessels during aging and produce the senescence-associated secretory phenotype (SASP). Age-related cardiovascular disease is promoted by SASP chronic inflammation. SASP establishment has been attributed to DNA damage and cGAS activation through cytoplasmic chromatin fragments. Therefore, DNA sensing has been extensively studied in cellular senescence; RNA sensing, on the other hand, remains unexplored. Here, we uncover a pivotal role for RNA accumulation and sensing in endothelial senescence. Our study suggests that intracellular RNA accumulation is a hallmark of senescent endothelial cells. This is associated with activation of RIG-I RNA sensing, and IRF7-driven IFN innate immune response. Moreover, our results revealed that inhibition of IRF7 or RIG-I were sufficient to extend the lifespan and functionality of endothelial cells. These data link the IFN gene signature with RNA accumulation/sensing in senescent endothelium and suggest IRF7 and RIG-I as potential therapeutic targets to delay vascular aging.

ORGANISM(S): Homo sapiens

PROVIDER: GSE160166 | GEO | 2023/10/23

REPOSITORIES: GEO

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