| First Author | Yang B | Year | 2021 |
| Journal | Aging Cell | Volume | 20 |
| Issue | 4 | Pages | e13329 |
| PubMed ID | 33734555 | Mgi Jnum | J:304856 |
| Mgi Id | MGI:6693576 | Doi | 10.1111/acel.13329 |
| Citation | Yang B, et al. (2021) NAD(+) supplementation prevents STING-induced senescence in ataxia telangiectasia by improving mitophagy. Aging Cell :e13329 |
| abstractText | Senescence phenotypes and mitochondrial dysfunction are implicated in aging and in premature aging diseases, including ataxia telangiectasia (A-T). Loss of mitochondrial function can drive age-related decline in the brain, but little is known about whether improving mitochondrial homeostasis alleviates senescence phenotypes. We demonstrate here that mitochondrial dysfunction and cellular senescence with a senescence-associated secretory phenotype (SASP) occur in A-T patient fibroblasts, and in ATM-deficient cells and mice. Senescence is mediated by stimulator of interferon genes (STING) and involves ectopic cytoplasmic DNA. We further show that boosting intracellular NAD(+) levels with nicotinamide riboside (NR) prevents senescence and SASP by promoting mitophagy in a PINK1-dependent manner. NR treatment also prevents neurodegeneration, suppresses senescence and neuroinflammation, and improves motor function in Atm(-/-) mice. Our findings suggest a central role for mitochondrial dysfunction-induced senescence in A-T pathogenesis, and that enhancing mitophagy as a potential therapeutic intervention. |
