| First Author | Hofmann JW | Year | 2015 |
| Journal | Cell | Volume | 160 |
| Issue | 3 | Pages | 477-88 |
| PubMed ID | 25619689 | Mgi Jnum | J:219563 |
| Mgi Id | MGI:5621203 | Doi | 10.1016/j.cell.2014.12.016 |
| Citation | Hofmann JW, et al. (2015) Reduced expression of MYC increases longevity and enhances healthspan. Cell 160(3):477-88 |
| abstractText | MYC is a highly pleiotropic transcription factor whose deregulation promotes cancer. In contrast, we find that Myc haploinsufficient (Myc(+/-)) mice exhibit increased lifespan. They show resistance to several age-associated pathologies, including osteoporosis, cardiac fibrosis, and immunosenescence. They also appear to be more active, with a higher metabolic rate and healthier lipid metabolism. Transcriptomic analysis reveals a gene expression signature enriched for metabolic and immune processes. The ancestral role of MYC as a regulator of ribosome biogenesis is reflected in reduced protein translation, which is inversely correlated with longevity. We also observe changes in nutrient and energy sensing pathways, including reduced serum IGF-1, increased AMPK activity, and decreased AKT, TOR, and S6K activities. In contrast to observations in other longevity models, Myc(+/-) mice do not show improvements in stress management pathways. Our findings indicate that MYC activity has a significant impact on longevity and multiple aspects of mammalian healthspan. |
