| First Author | Wong ES | Year | 2009 |
| Journal | Dev Cell | Volume | 17 |
| Issue | 1 | Pages | 142-9 |
| PubMed ID | 19619499 | Mgi Jnum | J:151980 |
| Mgi Id | MGI:4355650 | Doi | 10.1016/j.devcel.2009.05.009 |
| Citation | Wong ES, et al. (2009) p38MAPK controls expression of multiple cell cycle inhibitors and islet proliferation with advancing age. Dev Cell 17(1):142-9 |
| abstractText | Aging is a complex organismal process that is controlled by genetic, environmental, and behavioral factors. Accumulating evidence supports a role for different cell cycle inhibitors in mammalian aging. Little is known, however, about the upstream signals that induce their expression. Here, we explore the role of p38MAPK by generating a dominant-negative allele (p38(AF)) in which activating phosphorylation sites Thr180 and Tyr182 are mutated. Heterozygous p38(AF) mice show a marked attenuation of p38-dependent signaling and age-induced expression of multiple cell cycle inhibitors in different organs, including pancreatic islets. As a result, aged p38(AF/+) mice show enhanced proliferation and regeneration of islets when compared to wild-type littermates. We further find an age-related reduction in expression of the p38-specific phosphatase Wip1. Wip1-deficient mice demonstrate decreased islet proliferation, while Wip1 overexpression rescues aging-related decline in proliferation and regenerative capacity. We propose that modulation of p38MAPK activity may provide new avenues for treating certain age-related degenerative diseases. |
