| First Author | Yan L | Year | 2007 |
| Journal | Cell | Volume | 130 |
| Issue | 2 | Pages | 247-58 |
| PubMed ID | 17662940 | Mgi Jnum | J:145258 |
| Mgi Id | MGI:3834045 | Doi | 10.1016/j.cell.2007.05.038 |
| Citation | Yan L, et al. (2007) Type 5 adenylyl cyclase disruption increases longevity and protects against stress. Cell 130(2):247-58 |
| abstractText | Mammalian models of longevity are related primarily to caloric restriction and alterations in metabolism. We examined mice in which type 5 adenylyl cyclase (AC5) is knocked out (AC5 KO) and which are resistant to cardiac stress and have increased median lifespan of approximately 30%. AC5 KO mice are protected from reduced bone density and susceptibility to fractures of aging. Old AC5 KO mice are also protected from aging-induced cardiomyopathy, e.g., hypertrophy, apoptosis, fibrosis, and reduced cardiac function. Using a proteomic-based approach, we demonstrate a significant activation of the Raf/MEK/ERK signaling pathway and upregulation of cell protective molecules, including superoxide dismutase. Fibroblasts isolated from AC5 KO mice exhibited ERK-dependent resistance to oxidative stress. These results suggest that AC is a fundamentally important mechanism regulating lifespan and stress resistance. |
