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Calorie-Restriction-Induced Insulin Sensitivity Is Mediated by Adipose mTORC2 and Not Required for Lifespan Extension
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“Whole body deficiency of mTORC2 signaling, or tissue-specific inhibition of mTORC2 signaling in the brain, liver, or adipose tissue, reduces lifespan in C57BL/6J mice 114–117.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [114]
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“Genetic inhibition of mTORC2 in one or more tissues of a mouse can result in frailty, hyperphagia, insulin resistance, hyperlipidemia, hypercholesterolemia, hyperglycemia, kyphosis, and/or obesity depending upon the specific tissues in which mTORC2 is inhibited 114–117, 68.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [114]
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SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
Horton, J. D., Goldstein, J. L., & Brown, M. S. (2002) · Journal of Clinical Investigation · doi:10.1172/jci0215593 · Cited by 4,092
Adipocytes as regulators of energy balance and glucose homeostasis
Rosen, E. D., & Spiegelman, B. M. (2006) · Nature · doi:10.1038/nature05483 · Cited by 2,170 · cited 1×
“We found that AQ-RKO mice of both sexes were glucose tolerant (Figure 1F) but, as we anticipated given the established role of adipose tissue in insulin-stimulated glucose clearance (Rosen and Spiegelman, 2006), we observed that AQ-RKO mice were insulin resistant, with a more pronounced effect in male mice (Figure 1G).”
BackgroundIGF-1 receptor regulates lifespan and resistance to oxidative stress in mice
Holzenberger, M., Dupont, J., Ducos, B., Leneuve, P., Géloën, A., Even, P. C., Cervera, P., & Le Bouc, Y. (2003) · Nature · doi:10.1038/nature01298 · Cited by 2,109
Promoting Health and Longevity through Diet: From Model Organisms to Humans
Fontana, L., & Partridge, L. (2015) · Cell · doi:10.1016/j.cell.2015.02.020 · Cited by 1,245
mTOR inhibition improves immune function in the elderly
Mannick, J. B., Del Giudice, G., Lattanzi, M., Valiante, N. M., Praestgaard, J., Huang, B., Lonetto, M. A., Maecker, H. T., Kovarik, J., Carson, S., et al. (2014) · Science Translational Medicine · doi:10.1126/scitranslmed.3009892 · Cited by 786
mTORC1 in the Paneth cell niche couples intestinal stem-cell function to calorie intake
Yilmaz, Ö. H., Katajisto, P., Lamming, D. W., Gültekin, Y., Bauer-Rowe, K. E., Sengupta, S., Birsoy, K., Dursun, A., Yilmaz, V. O., Selig, M., et al. (2012) · Nature · doi:10.1038/nature11163 · Cited by 753
Self-citationTissue-specific regulation of SIRT1 by calorie restriction
Chen, D., Bruno, J., Easlon, E., Lin, S.-J., Cheng, H.-L., Alt, F. W., & Guarente, L. (2008) · Genes & Development · doi:10.1101/gad.1650608 · Cited by 567
Selman, C., Lingard, S., Choudhury, A. I., Batterham, R. L., Claret, M., Clements, M., Ramadani, F., Okkenhaug, K., Schuster, E., Blanc, E., et al. (2008) · The FASEB Journal · doi:10.1096/fj.07-9261com · Cited by 532
TORC1 inhibition enhances immune function and reduces infections in the elderly
Mannick, J. B., Morris, M., Hockey, H.-U. P., Roma, G., Beibel, M., Kulmatycki, K., Watkins, M., Shavlakadze, T., Zhou, W., Quinn, D., et al. (2018) · Science Translational Medicine · doi:10.1126/scitranslmed.aaq1564 · Cited by 496
Tumours with PI3K activation are resistant to dietary restriction
Kalaany, N. Y., & Sabatini, D. M. (2009) · Nature · doi:10.1038/nature07782 · Cited by 468
Flagged first, then by citations
Research works printed but not linked: 52
- Arriola Apelo, 2016, Rapamycin: an inhibitor of aging emerges from the soil of Easter Island, J. Gerontol. A Biol. Sci. Med. Sci., 71, 841, 10.1093/gerona/glw090 · DOI
- Baar, 2016, Sex- and tissue-specific changes in mTOR signaling with age in C57BL/6J mice, Aging Cell, 15, 155, 10.1111/acel.12425 · DOI · Paper page
- Balasubramanian, 2017, Aging and caloric restriction research: a biological perspective with translational potential, EBioMedicine, 21, 37, 10.1016/j.ebiom.2017.06.015 · DOI · Paper page
- Blagosklonny, 2012, Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to, Aging (Albany N.Y.), 4, 350
- Blüher, 2003, Extended longevity in mice lacking the insulin receptor in adipose tissue, Science, 299, 572, 10.1126/science.1078223 · DOI · Paper page
- Bruss, 2010, Calorie restriction increases fatty acid synthesis and whole body fat oxidation rates, Am. J. Physiol. Endocrinol. Metab., 298, E108, 10.1152/ajpendo.00524.2009 · DOI
- Chellappa, 2019, Hypothalamic mTORC2 is essential for metabolic health and longevity, Aging Cell, 18, e13014, 10.1111/acel.13014 · DOI · Paper page
- Cummings, 2018, Restoration of metabolic health by decreased consumption of branched-chain amino acids, J. Physiol., 596, 623, 10.1113/JP275075 · DOI
- Cybulski, 2009, mTOR complex 2 in adipose tissue negatively controls whole-body growth, Proc. Natl. Acad. Sci. USA, 106, 9902, 10.1073/pnas.0811321106 · DOI
- Dumas, 2019, Next generation strategies for geroprotection via mTORC1 inhibition, J. Gerontol. A Biol. Sci. Med. Sci., glz056
- Eguchi, 2011, Transcriptional control of adipose lipid handling by IRF4, Cell Metab., 13, 249, 10.1016/j.cmet.2011.02.005 · DOI
- Evans, 2013, Aging and insulin resistance: just say iNOS, Diabetes, 62, 346, 10.2337/db12-1239 · DOI
- Fabbiano, 2016, Caloric restriction leads to browning of white adipose tissue through type 2 immune signaling, Cell Metab., 24, 434, 10.1016/j.cmet.2016.07.023 · DOI
- Garratt, 2017, Sex differences in lifespan extension with acarbose and 17-α estradiol: gonadal hormones underlie male-specific improvements in glucose tolerance and mTORC2 signaling, Aging Cell, 16, 1256, 10.1111/acel.12656 · DOI · Paper page
- Guertin, 2006, Ablation in mice of the mTORC components raptor, rictor, or mLST8 reveals that mTORC2 is required for signaling to Akt-FOXO and PKCalpha, but not S6K1, Dev. Cell, 11, 859, 10.1016/j.devcel.2006.10.007 · DOI
- Hagiwara, 2012, Hepatic mTORC2 activates glycolysis and lipogenesis through Akt, glucokinase, and SREBP1c, Cell Metab., 15, 725, 10.1016/j.cmet.2012.03.015 · DOI
- Harrison, 2019, Acarbose improves health and lifespan in aging HET3 mice, Aging Cell, 18, e12898, 10.1111/acel.12898 · DOI
- Hasek, 2010, Dietary methionine restriction enhances metabolic flexibility and increases uncoupled respiration in both fed and fasted states, Am. J. Physiol. Regul. Integr. Comp. Physiol., 299, R728, 10.1152/ajpregu.00837.2009 · DOI
- Herman, 2012, A novel ChREBP isoform in adipose tissue regulates systemic glucose metabolism, Nature, 484, 333, 10.1038/nature10986 · DOI
- Kane, 2016, Impact of longevity interventions on a validated mouse clinical frailty index, J. Gerontol. A Biol. Sci. Med. Sci., 71, 333, 10.1093/gerona/glu315 · DOI
- Kennedy, 2016, The mechanistic target of rapamycin: the grand conductor of metabolism and aging, Cell Metab., 23, 990, 10.1016/j.cmet.2016.05.009 · DOI · Paper page
- Kenyon, 2001, A conserved regulatory system for aging, Cell, 105, 165, 10.1016/S0092-8674(01)00306-3 · DOI
- Kraig, 2018, A randomized control trial to establish the feasibility and safety of rapamycin treatment in an older human cohort: immunological, physical performance, and cognitive effects, Exp. Gerontol., 105, 53, 10.1016/j.exger.2017.12.026 · DOI · Paper page
- Kumar, 2008, Muscle-specific deletion of rictor impairs insulin-stimulated glucose transport and enhances basal glycogen synthase activity, Mol. Cell. Biol., 28, 61, 10.1128/MCB.01405-07 · DOI
- Kumar, 2010, Fat cell-specific ablation of rictor in mice impairs insulin-regulated fat cell and whole-body glucose and lipid metabolism, Diabetes, 59, 1397, 10.2337/db09-1061 · DOI
- Lamming, 2014, Diminished mTOR signaling: a common mode of action for endocrine longevity factors, Springerplus, 3, 735, 10.1186/2193-1801-3-735 · DOI · Paper page
- Lamming, 2012, Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity, Science, 335, 1638, 10.1126/science.1215135 · DOI · Paper page
- Lamming, 2014, Hepatic signaling by the mechanistic target of rapamycin complex 2 (mTORC2), FASEB J., 28, 300, 10.1096/fj.13-237743 · DOI
- Lamming, 2014, Depletion of Rictor, an essential protein component of mTORC2, decreases male lifespan, Aging Cell, 13, 911, 10.1111/acel.12256 · DOI · Paper page
- Linnemann, 2015, Glucagon-like peptide-1 regulates cholecystokinin production in β-cells to protect from apoptosis, Mol. Endocrinol., 29, 978, 10.1210/me.2015-1030 · DOI
- López-Lluch, 2016, Calorie restriction as an intervention in ageing, J. Physiol., 594, 2043, 10.1113/JP270543 · DOI
- Madeo, 2019, Caloric restriction mimetics against age-associated disease: targets, mechanisms, and therapeutic potential, Cell Metab., 29, 592, 10.1016/j.cmet.2019.01.018 · DOI · Paper page
- Most, 2017, Calorie restriction in humans: An update, Ageing Res. Rev., 39, 36, 10.1016/j.arr.2016.08.005 · DOI · Paper page
- Nojima, 2013, Haploinsufficiency of akt1 prolongs the lifespan of mice, PLoS ONE, 8, e69178, 10.1371/journal.pone.0069178 · DOI
- Pearson, 2008, Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction, Proc. Natl. Acad. Sci. USA, 105, 2325, 10.1073/pnas.0712162105 · DOI
- Rockwood, 2017, A frailty index based on deficit accumulation quantifies mortality risk in humans and in mice, Sci. Rep., 7, 43068, 10.1038/srep43068 · DOI
- Sarbassov, 2005, Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex, Science, 307, 1098, 10.1126/science.1106148 · DOI · Paper page
- Schneider, 2012, NIH Image to ImageJ: 25 years of image analysis, Nat. Methods, 9, 671, 10.1038/nmeth.2089 · DOI · Paper page
- Schreiber, 2015, Rapamycin-mediated mTORC2 inhibition is determined by the relative expression of FK506-binding proteins, Aging Cell, 14, 265, 10.1111/acel.12313 · DOI
- Schreiber, 2019, A novel rapamycin analog is highly selective for mTORC1 in vivo, Nat. Commun., 10, 3194, 10.1038/s41467-019-11174-0 · DOI · Paper page
- Shiota, 2006, Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability, Dev. Cell, 11, 583, 10.1016/j.devcel.2006.08.013 · DOI
- Solon-Biet, 2015, Dietary protein to carbohydrate ratio and caloric restriction: comparing metabolic outcomes in mice, Cell Rep., 11, 1529, 10.1016/j.celrep.2015.05.007 · DOI · Paper page
- Tang, 2016, Adipose tissue mTORC2 regulates ChREBP-driven de novo lipogenesis and hepatic glucose metabolism, Nat. Commun., 7, 11365, 10.1038/ncomms11365 · DOI
- Templeman, 2017, Reduced circulating insulin enhances insulin sensitivity in old mice and extends lifespan, Cell Rep., 20, 451, 10.1016/j.celrep.2017.06.048 · DOI
- Tran, 2016, Rapamycin blocks induction of the thermogenic program in white adipose tissue, Diabetes, 65, 927, 10.2337/db15-0502 · DOI
- Uyeda, 2006, Carbohydrate response element binding protein, ChREBP, a transcription factor coupling hepatic glucose utilization and lipid synthesis, Cell Metab., 4, 107, 10.1016/j.cmet.2006.06.008 · DOI
- Vijayakumar, 2017, Absence of carbohydrate response element binding protein in adipocytes causes systemic insulin resistance and impairs glucose transport, Cell Rep., 21, 1021, 10.1016/j.celrep.2017.09.091 · DOI
- Whitehead, 2014, A clinical frailty index in aging mice: comparisons with frailty index data in humans, J. Gerontol. A Biol. Sci. Med. Sci., 69, 621, 10.1093/gerona/glt136 · DOI
- Williamson, 2012, Insulin resistance in the brain: an old-age or new-age problem?, Biochem. Pharmacol., 84, 737, 10.1016/j.bcp.2012.05.007 · DOI
- Yore, 2014, Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects, Cell, 159, 318, 10.1016/j.cell.2014.09.035 · DOI
- Yu, 2018, Short-term methionine deprivation improves metabolic health via sexually dimorphic, mTORC1-independent mechanisms, FASEB J., 32, 3471, 10.1096/fj.201701211R · DOI
- Yuan, 2012, Identification of Akt-independent regulation of hepatic lipogenesis by mammalian target of rapamycin (mTOR) complex 2, J. Biol. Chem., 287, 29579, 10.1074/jbc.M112.386854 · DOI
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Molecular mechanisms of dietary restriction promoting health and longevity
Green, C. L., Lamming, D. W., & Fontana, L. (2022) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-021-00411-4 · Cited by 714
Self-citationTargeting the biology of aging with mTOR inhibitors
Mannick, J. B., & Lamming, D. W. (2023) · Nature Aging · doi:10.1038/s43587-023-00416-y · Cited by 372
Self-citationPak, H. H., Haws, S. A., Green, C. L., Koller, M., Lavarias, M. T., Richardson, N. E., Yang, S. E., Dumas, S. N., Sonsalla, M., Bray, L., et al. (2021) · Nature Metabolism · doi:10.1038/s42255-021-00466-9 · Cited by 171
Self-citationThe role of ChREBP in carbohydrate sensing and NAFLD development
Régnier, M., Carbinatti, T., Parlati, L., Benhamed, F., & Postic, C. (2023) · Nature Reviews Endocrinology · doi:10.1038/s41574-023-00809-4 · Cited by 101
Napoleão, A., Fernandes, L., Miranda, C., & Marum, A. P. (2021) · Nutrients · doi:10.3390/nu13041302 · Cited by 103
Resistance exercise protects mice from protein-induced fat accretion
Trautman, M. E., Braucher, L. N., Elliehausen, C., Zhu, W. G., Zelenovskiy, E., Green, M., Sonsalla, M. M., Yeh, C.-Y., Hornberger, T. A., Konopka, A. R., et al. (2023) · eLife · doi:10.7554/elife.91007 · Cited by 8
Self-citationResistance exercise protects mice from protein-induced fat accretion
Trautman, M. E., Braucher, L. N., Elliehausen, C., Zhu, W. G., Zelenovskiy, E., Green, M., Sonsalla, M. M., Yeh, C.-Y., Hornberger, T. A., Konopka, A. R., et al. (2023) · doi:10.7554/elife.91007.2 · Cited by 1
Self-citation
Metadata
- Authors
- Yu, D., Tomasiewicz, J. L., Yang, S. E., Miller, B. R., Wakai, M. H., Sherman, D. S., Cummings, N. E., Baar, E. L., Brinkman, J. A., Syed, F. A., & Lamming, D. W.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2019-10
- Volume
- 29
- Issue
- 1
- Pages
- 236-248.e3
- ISSN
- 2211-1247
- PMC
- PMC6820997
- Cited by
- 98
- References
- 15
- Language
- en
- Licence
- Funders
- National Institutes of Health
- National Cancer Institute
- Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison
- Glenn Foundation for Medical Research
- American Federation for Aging Research
- American Foundation for Aging Research
- School of Medicine and Public Health, University of Wisconsin-Madison
- U.S. Department of Veterans Affairs (I01-BX004031)
- National Center for Advancing Translational Sciences (UL1TR002373)
- National Institute on Aging (AG041765, AG056771, AG051974, AG050135, AG062328, T32 AG000213)
- University of Wisconsin-Madison
- University of Wisconsin Carbone Cancer Center (P30 CA014520)
- American Heart Association (17PRE33410983)
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