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- W3146591907 endingPage "2052.e6" @default.
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- W3146591907 abstract "Cellular senescence is a state of stable proliferative arrest triggered by damaging signals. Senescent cells persist during aging and promote age-related pathologies via the pro-inflammatory senescence-associated secretory phenotype (SASP), whose regulation depends on environmental factors. In vivo, a major environmental variable is oxygenation, which varies among and within tissues. Here, we demonstrate that senescent cells express lower levels of detrimental pro-inflammatory SASP factors in physiologically hypoxic environments, as measured in culture and in tissues. Mechanistically, exposure of senescent cells to low-oxygen conditions leads to AMPK activation and AMPK-mediated suppression of the mTOR-NF-κB signaling loop. Finally, we demonstrate that treatment with hypoxia-mimetic compounds reduces SASP in cells and tissues and improves strength in chemotherapy-treated and aged mice. Our findings highlight the importance of oxygen as a determinant for pro-inflammatory SASP expression and offer a potential new strategy to reduce detrimental paracrine effects of senescent cells." @default.
- W3146591907 created "2021-04-13" @default.
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- W3146591907 date "2021-05-01" @default.
- W3146591907 modified "2023-10-17" @default.
- W3146591907 title "Physiological hypoxia restrains the senescence-associated secretory phenotype via AMPK-mediated mTOR suppression" @default.
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- W3146591907 doi "https://doi.org/10.1016/j.molcel.2021.03.018" @default.
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