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 - Funding Information:
This work was supported by NIH grant R37 AG016694 to J.M.S. J.W.H. was supported in part by grant F30 AG035592. J.M.S. was a Senior Scholar of the Ellison Medical Foundation and a recipient of the Glenn Award for Research on the Biological Mechanisms of Aging. The Brown Molecular Pathology and Genomics core facilities were supported by NIH grants P42 ES013660 and P30 GM103410. R.dC. is funded by the Intramural Research Program of the National Institute on Aging (NIH).
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 -