Reduced expression of MYC increases longevity and enhances healthspan

Jeffrey W. Hofmann, Xiaoai Zhao, Marco De Cecco, Abigail L. Peterson, Luca Pagliaroli, Jayameenakshi Manivannan, Gene B. Hubbard, Yuji Ikeno, Yongqing Zhang, Bin Feng, Xiaxi Li, Thomas Serre, Wenbo Qi, Holly Van Remmen, Richard A. Miller, Kevin G. Bath, Rafael De Cabo, Haiyan Xu, Nicola Neretti, John M. Sedivy

Producción científica: Articlerevisión exhaustiva

211 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)477-488
Número de páginas12
PublicaciónCell
Volumen160
N.º3
DOI
EstadoPublished - ene 29 2015

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology

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