| First Author | van Vliet T | Year | 2021 |
| Journal | Mol Cell | Volume | 81 |
| Issue | 9 | Pages | 2041-2052.e6 |
| PubMed ID | 33823141 | Mgi Jnum | J:311383 |
| Mgi Id | MGI:6707971 | Doi | 10.1016/j.molcel.2021.03.018 |
| Citation | van Vliet T, et al. (2021) Physiological hypoxia restrains the senescence-associated secretory phenotype via AMPK-mediated mTOR suppression. Mol Cell 81(9):2041-2052.e6 |
| abstractText | 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-kappaB 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. |
