Reduced Expression of MYC Increases Longevity and Enhances Healthspan

Cell. 2015 Jan 29;160(3):477-88. doi: 10.1016/j.cell.2014.12.016. Epub 2015 Jan 22.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging
  • Animals
  • Body Size
  • Female
  • Longevity
  • Lymphoma / genetics
  • Male
  • Metabolic Networks and Pathways
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Proto-Oncogene Proteins c-myc / genetics*
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Transcriptome

Substances

  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc

Associated data

  • GEO/GSE55272