| First Author | Wiley CD | Year | 2016 |
| Journal | Cell Metab | Volume | 23 |
| Issue | 2 | Pages | 303-14 |
| PubMed ID | 26686024 | Mgi Jnum | J:232814 |
| Mgi Id | MGI:5780257 | Doi | 10.1016/j.cmet.2015.11.011 |
| Citation | Wiley CD, et al. (2016) Mitochondrial Dysfunction Induces Senescence with a Distinct Secretory Phenotype. Cell Metab 23(2):303-14 |
| abstractText | Cellular senescence permanently arrests cell proliferation, often accompanied by a multi-faceted senescence-associated secretory phenotype (SASP). Loss of mitochondrial function can drive age-related declines in the function of many post-mitotic tissues, but little is known about how mitochondrial dysfunction affects mitotic tissues. We show here that several manipulations that compromise mitochondrial function in proliferating human cells induce a senescence growth arrest with a modified SASP that lacks the IL-1-dependent inflammatory arm. Cells that underwent mitochondrial dysfunction-associated senescence (MiDAS) had lower NAD+/NADH ratios, which caused both the growth arrest and prevented the IL-1-associated SASP through AMPK-mediated p53 activation. Progeroid mice that rapidly accrue mtDNA mutations accumulated senescent cells with a MiDAS SASP in vivo, which suppressed adipogenesis and stimulated keratinocyte differentiation in cell culture. Our data identify a distinct senescence response and provide a mechanism by which mitochondrial dysfunction can drive aging phenotypes. |
