Cited by 195Genetics, Aging, and Longevity in Model OrganismsPI3K/AKT/mTOR signaling in cancerMetabolism, Diabetes, and Cancer

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Duration of Rapamycin Treatment Has Differential Effects on Metabolism in Mice

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Fang, Yimin, Westbrook, Reyhan, Hill, Cristal, Boparai, Ravneet K., Arum, Oge, Spong, Adam, Wang, Feiya, Javors, Martin A., Chen, Jie, Sun, Liou Y., Bartke, Andrzej·2013·Cell Metabolism

DOI 10.1016/j.cmet.2013.02.008PMC PMC3658445

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Abstract

The evolutionarily conserved target of rapamycin (TOR) signaling controls growth, metabolism, and aging. In the first robust demonstration of pharmacologically-induced life extension in mammals, longevity was extended in mice treated with rapamycin, an inhibitor of mechanistic TOR (mTOR). However, detrimental metabolic effects of rapamycin treatment were also reported, presenting a paradox of improved survival despite metabolic impairment. How rapamycin extended lifespan in mice with such paradoxical effects was unclear. Here we show that detrimental effects of rapamycin treatment were only observed during the early stages of treatment. These effects were reversed or diminished in mice treated for 20 weeks, with better metabolic profiles, increased oxygen consumption and ketogenesis, and markedly enhanced insulin sensitivity. Thus, prolonged rapamycin treatment lead to beneficial metabolic alterations, consistent with life extension previously observed. Our findings provide a likely explanation of the "rapamycin paradox" and support the potential causal importance of these metabolic alterations in longevity.

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1 retracted

Disruption of Growth Hormone Receptor Prevents Calorie Restriction from Improving Insulin Action and Longevity
Bonkowski, M. S., Dominici, F. P., Arum, O., Rocha, J. S., Al-Regaiey, K., Westbrook, R., Spong, A., Panici, J. A., Masternak, M. M., Kopchick, J. J., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0004567 · Cited by 125
Self-citation
Retracted
TOR signaling in growth and metabolism
Wullschleger, S., Loewith, R., & Hall, M. N. (2006) · Cell · doi:10.1016/j.cell.2006.01.016 · Cited by 5,787
Rapamycin fed late in life extends lifespan in genetically heterogeneous mice
Harrison, D. E., Strong, R., Sharp, Z. D., Nelson, J. F., Astle, C. M., Flurkey, K., Nadon, N. L., Wilkinson, J. E., Frenkel, K., Carter, C. S., et al. (2009) · Nature · doi:10.1038/nature08221 · Cited by 3,766
Self-citation
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Sarbassov, D. D., Ali, S. M., Sengupta, S., Sheen, J.-H., Hsu, P. P., Bagley, A. F., Markhard, A. L., & Sabatini, D. M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.03.029 · Cited by 2,365
mTOR controls mitochondrial oxidative function through a YY1–PGC-1α transcriptional complex
Cunningham, J. T., Rodgers, J. T., Arlow, D. H., Vazquez, F., Mootha, V. K., & Puigserver, P. (2007) · Nature · doi:10.1038/nature06322 · Cited by 1,488
Rapamycin-Induced Insulin Resistance Is Mediated by mTORC2 Loss and Uncoupled from Longevity
Lamming, D. W., Ye, L., Katajisto, P., Goncalves, M. D., Saitoh, M., Stevens, D. M., Davis, J. G., Salmon, A. B., Richardson, A., Ahima, R. S., et al. (2012) · Science · doi:10.1126/science.1215135 · Cited by 1,199
Ribosomal Protein S6 Kinase 1 Signaling Regulates Mammalian Life Span
Selman, C., Tullet, J. M. A., Wieser, D., Irvine, E., Lingard, S. J., Choudhury, A. I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. (2009) · Science · doi:10.1126/science.1177221 · Cited by 1,120
The Critical Role of Metabolic Pathways in Aging
Barzilai, N., Huffman, D. M., Muzumdar, R. H., & Bartke, A. (2012) · Diabetes · doi:10.2337/db11-1300 · Cited by 803
Self-citation
S6K1 −/− / S6K2 −/− Mice Exhibit Perinatal Lethality and Rapamycin-Sensitive 5′-Terminal Oligopyrimidine mRNA Translation and Reveal a Mitogen-Activated Protein Kinase-Dependent S6 Kinase Pathway
Pende, M., Um, S. H., Mieulet, V., Sticker, M., Goss, V. L., Mestan, J., Mueller, M., Fumagalli, S., Kozma, S. C., & Thomas, G. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.8.3112-3124.2004 · Cited by 766
Bifurcation of insulin signaling pathway in rat liver: mTORC1 required for stimulation of lipogenesis, but not inhibition of gluconeogenesis
Li, S., Brown, M. S., & Goldstein, J. L. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0914798107 · Cited by 733 · cited 2×
“…and hypertriglyceridemia occur (Matsumoto et al., 2006). mTORC1 is required for insulin-induced stimulation of lipogenesis but not for inhibition of gluconeogenesis (Li et al., 2010), and 2 weeks of rapamycin treatment inhibited lipogenesis and upregulated gluconeogenesis (Houde et al., 2010).”

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Wang, R., Yu, Z., Sunchu, B., Shoaf, J., Dang, I., Zhao, S., Caples, K., Bradley, L., Beaver, L. M., Ho, E., et al. (2017) · Aging Cell · doi:10.1111/acel.12587 · Cited by 360
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Dai, D., Karunadharma, P. P., Chiao, Y. A., Basisty, N., Crispin, D. A., Hsieh, E. J., Chen, T., Gu, H., Djukovic, D., Raftery, D., et al. (2014) · Aging Cell · doi:10.1111/acel.12203 · Cited by 327
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Khaibullina, A., Almeida, L. E. F., Wang, L., Kamimura, S., Wong, E. C. C., Nouraie, M. S., Marić, I., Albani, S. H., Finkel, J. C., & Quezado, Z. (2015) · Blood Cells Molecules and Diseases · doi:10.1016/j.bcmd.2015.08.001 · Cited by 42
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Selman, C. (2014) · Proceedings of The Nutrition Society · doi:10.1017/s0029665113003832 · Cited by 44
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Austad, S. N. (2016) · Advances in Geroscience · doi:10.1007/978-3-319-23246-1_1 · Cited by 43
Lifespan Modulation in Mice and the Confounding Effects of Genetic Background
Mulvey, L., Sinclair, A., & Selman, C. (2014) · Journal of genetics and genomics/Journal of Genetics and Genomics · doi:10.1016/j.jgg.2014.06.002 · Cited by 40
Long-term administration of tacrolimus and everolimus prevents high cholesterol-high fructose-induced steatosis in C57BL/6J mice by inhibiting de-novo lipogenesis
Love, S., Mudasir, M. A., Bhardwaj, S. C., Singh, G., & Abdullah, S. T. (2017) · Oncotarget · doi:10.18632/oncotarget.15194 · Cited by 40
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Chronic rapamycin treatment causes diabetes in male mice
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Rocchi, A., & He, C. (2017) · Journal of Visualized Experiments · doi:10.3791/55099 · Cited by 39
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Shariff, A. I., Syed, S. H., Shelby, R. A., Force, J. M., Clarke, J. M., D’Alessio, D. A., & Corsino, L. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0002 · Cited by 38
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Moderate lifelong overexpression of tuberous sclerosis complex 1 (TSC1) improves health and survival in mice
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Autophagy and lysosomal pathways in nervous system disorders
Bingol, B. (2018) · Molecular and Cellular Neuroscience · doi:10.1016/j.mcn.2018.04.009 · Cited by 32
A ride through the epigenetic landscape: aging reversal by reprogramming
Camillo, L. P. D. L., & Quinlan, R. B. A. (2021) · GeroScience · doi:10.1007/s11357-021-00358-6 · Cited by 30
Specific suppression of insulin sensitivity in growth hormone receptor gene‐disrupted ( GHR ‐ KO ) mice attenuates phenotypic features of slow aging
Arum, O., Boparai, R. K., Saleh, J. K., Wang, F., Dirks, A. L., Turner, J. G., Kopchick, J. J., Liu, J., Khardori, R. K., & Bartke, A. (2014) · Aging Cell · doi:10.1111/acel.12262 · Cited by 31
Self-citation
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Scarpace, P. J., Matheny, M. E., Strehler, K. Y. E., Toklu, H. Z., Kirichenko, N., Carter, C. S., Morgan, D., & Tümer, N. (2015) · The Journals of Gerontology Series A · doi:10.1093/gerona/glu230 · Cited by 31
Reduced expression of C/EBPβ-LIP extends health and lifespan in mice
Müller, C., Zidek, L. M., Ackermann, T., de Jong, T. V., Liu, P., Kliche, V., Zaini, M. A., Kortman, G., Harkema, L., Verbeek, D. S., et al. (2018) · eLife · doi:10.7554/elife.34985 · Cited by 31
mTORC1 restrains adipocyte lipolysis to prevent systemic hyperlipidemia
Paolella, L. M., Mukherjee, S., Tran, C. M., Bellaver, B., Hugo, M., Luongo, T. S., Shewale, S. V., Lu, W., Chellappa, K., & Baur, J. A. (2019) · Molecular Metabolism · doi:10.1016/j.molmet.2019.12.003 · Cited by 33
Extending lifespan by modulating the growth hormone/insulin-like growth factor-1 axis: coming of age
Duran‐Ortiz, S., List, E. O., Basu, R., & Kopchick, J. J. (2021) · Pituitary · doi:10.1007/s11102-020-01117-0 · Cited by 30
Innate immune cell-intrinsic ketogenesis is dispensable for organismal metabolism and age-related inflammation
Goldberg, E. L., Letian, A., Dlugos, T., Leveau, C., & Dixit, V. D. (2023) · Journal of Biological Chemistry · doi:10.1016/j.jbc.2023.103005 · Cited by 31

Authors: Fang, Y., Westbrook, R., Hill, C., Boparai, R. K., Arum, O., Spong, A., Wang, F., Javors, M. A., Chen, J., Sun, L. Y., & Bartke, A.
Affiliations: SIU Medicine (US)
Southern Illinois University Carbondale (US)
The University of Texas at San Antonio Health Science Center (US)
University of Illinois Urbana-Champaign (US)
Corresponding author: Fang, Yimin
ORCID: Fang, Yimin
Westbrook, Reyhan
Hill, Cristal
Boparai, Ravneet K.
Arum, Oge
Wang, Feiya
Javors, Martin A.
Chen, Jie
Sun, Liou Y.
Bartke, Andrzej
Venue: Cell Metabolism
Publisher: Elsevier BV
Published: 2013-03
Volume: 17
Issue: 3
Pages: 456-462
ISSN: 1550-4131 (ISSN-L)
DOI: 10.1016/j.cmet.2013.02.008
PMC: PMC3658445
OpenAlex: W2001399616
Cited by: 195
References: 23
Citations by year: 2026: 6 · 2025: 5 · 2024: 8 · 2023: 7 · 2022: 13 · 2021: 20 · 2020: 11 · 2019: 21 · 2018: 14 · 2017: 15 · 2016: 18 · 2015: 26 · 2014: 20 · 2013: 10
FWCI: 8.75
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 369 d)
Locations: Cell Metabolism (publishedVersion)
PubMed (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
Funders: National Institutes of Health
Office of Public Affairs
National Institute on Aging (AG031736, R21AG038850, R01AG019899, AG038850, P01AG031736, AG019899)
National Institute of General Medical Sciences (R01GM089771)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR048914)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Keywords: rapamycin, mTOR signaling, longevity, lifespan extension, metabolic effects, insulin sensitivity, oxygen consumption, ketogenesis, treatment duration, aging
MeSH terms: Animals, Blood Chemical Analysis, Body Composition, Calorimetry, Indirect, Energy Metabolism, Enzyme-Linked Immunosorbent Assay, Insulin Resistance, Longevity, Oxygen Consumption, Time Factors, Blotting, Western, Sirolimus, Mice, TOR Serine-Threonine Kinases

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Duration of Rapamycin Treatment Has Differential Effects on Metabolism in Mice

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