| First Author | Yu DM | Year | 2017 |
| Journal | Aging Cell | Volume | 16 |
| Issue | 4 | Pages | 773-784 |
| PubMed ID | 28514055 | Mgi Jnum | J:318457 |
| Mgi Id | MGI:6859736 | Doi | 10.1111/acel.12606 |
| Citation | Yu DM, et al. (2017) Caveolin-1 deficiency induces premature senescence with mitochondrial dysfunction. Aging Cell 16(4):773-784 |
| abstractText | Paradoxical observations have been made regarding the role of caveolin-1 (Cav-1) during cellular senescence. For example, caveolin-1 deficiency prevents reactive oxygen species-induced cellular senescence despite mitochondrial dysfunction, which leads to senescence. To resolve this paradox, we re-addressed the role of caveolin-1 in cellular senescence in human diploid fibroblasts, A549, HCT116, and Cav-1(-/-) mouse embryonic fibroblasts. Cav-1 deficiency (knockout or knockdown) induced cellular senescence via a p53-p21-dependent pathway, downregulating the expression level of the cardiolipin biosynthesis enzymes and then reducing the content of cardiolipin, a critical lipid for mitochondrial respiration. Our results showed that Cav-1 deficiency decreased mitochondrial respiration, reduced the activity of oxidative phosphorylation complex I (CI), inactivated SIRT1, and decreased the NAD(+) /NADH ratio. From these results, we concluded that Cav-1 deficiency induces premature senescence via mitochondrial dysfunction and silent information regulator 2 homologue 1 (SIRT1) inactivation. |
