Cited by 293Genetics, Aging, and Longevity in Model OrganismsTelomeres, Telomerase, and SenescenceMetabolism, Diabetes, and Cancer

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Reduced Expression of MYC Increases Longevity and Enhances Healthspan

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Hofmann, Jeffrey W., Zhao, Xiaoai, De Cecco, Marco, Peterson, Abigail L., Pagliaroli, Luca, Manivannan, Jayameenakshi, Hubbard, Gene B., Ikeno, Yuji, Zhang, Yongqing, Feng, Bin, Li, Xiaxi, Serre, Thomas, Qi, Wenbo, Van Remmen, Holly, Miller, Richard A., Bath, Kevin G., de Cabo, Rafael, Xu, Haiyan, Neretti, Nicola, Sedivy, John M.·2015·Cell

DOI 10.1016/j.cell.2014.12.016PMC PMC4624921

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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.

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Authors: Hofmann, J. W., Zhao, X., De Cecco, M., Peterson, A. L., Pagliaroli, L., Manivannan, J., Hubbard, G. B., Ikeno, Y., Zhang, Y., Feng, B., Li, X., Serre, T., Qi, W., Van Remmen, H., Miller, R. A., Bath, K. G., de Cabo, R., Xu, H., Neretti, N., & Sedivy, J. M.
Affiliations: Brown University (US)
The University of Texas at San Antonio Health Science Center (US)
National Institute on Aging (US)
University of Michigan (US)
Corresponding author: Sedivy, John M.
ORCID: Hofmann, Jeffrey W.
Zhao, Xiaoai
Pagliaroli, Luca
Ikeno, Yuji
Zhang, Yongqing
Feng, Bin
Qi, Wenbo
Miller, Richard A.
Bath, Kevin G.
Xu, Haiyan
Neretti, Nicola
Sedivy, John M.
Venue: Cell
Publisher: Elsevier BV
Published: 2015-01
Volume: 160
Issue: 3
Pages: 477-488
ISSN: 0092-8674 (ISSN-L)
DOI: 10.1016/j.cell.2014.12.016
PMC: PMC4624921
OpenAlex: W2019755675
Cited by: 293
References: 118
Citations by year: 2026: 12 · 2025: 21 · 2024: 23 · 2023: 35 · 2022: 30 · 2021: 34 · 2020: 38 · 2019: 24 · 2018: 17 · 2017: 24 · 2016: 21 · 2015: 14
FWCI: 10.15
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 393 d)
Locations: Cell (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: U.S. Department of Veterans Affairs (I01 BX002595)
National Institutes of Health (1s10od016366-01, 5p42es013660-14)
National Institute on Aging (R37AG016694, P01AG031736, F30AG035592, R01AG016694, P30AG024824, U01AG022303)
National Institute of General Medical Sciences (P30GM103410)
National Institute of Environmental Health Sciences (P42ES013660),)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: c-Myc, haploinsufficiency, longevity, healthspan, aging, ribosome biogenesis, mRNA translation, insulin-like growth factor I, AMPK, TOR signaling, S6K, immunosenescence, myocardial fibrosis, osteoporosis, lipid metabolism, metabolic rate, energy sensing
MeSH terms: Aging, Animals, Female, Longevity, Lymphoma, Male, Mice, Inbred C57BL, Proto-Oncogene Proteins c-myc, Body Size, Mice, Metabolic Networks and Pathways, Mice, 129 Strain, Transcriptome

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Reduced Expression of MYC Increases Longevity and Enhances Healthspan

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