TY - JOUR
T1 - Reduced expression of MYC increases longevity and enhances healthspan
AU - Hofmann, Jeffrey W.
AU - Zhao, Xiaoai
AU - De Cecco, Marco
AU - Peterson, Abigail L.
AU - Pagliaroli, Luca
AU - Manivannan, Jayameenakshi
AU - Hubbard, Gene B.
AU - Ikeno, Yuji
AU - Zhang, Yongqing
AU - Feng, Bin
AU - Li, Xiaxi
AU - Serre, Thomas
AU - Qi, Wenbo
AU - Van Remmen, Holly
AU - Miller, Richard A.
AU - Bath, Kevin G.
AU - De Cabo, Rafael
AU - Xu, Haiyan
AU - Neretti, Nicola
AU - Sedivy, John M.
N1 - Publisher Copyright:
© 2015 Elsevier Inc.
PY - 2015/1/29
Y1 - 2015/1/29
N2 - 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.
AB - 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.
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U2 - 10.1016/j.cell.2014.12.016
DO - 10.1016/j.cell.2014.12.016
M3 - Article
C2 - 25619689
AN - SCOPUS:84922178023
SN - 0092-8674
VL - 160
SP - 477
EP - 488
JO - Cell
JF - Cell
IS - 3
ER -