Regulation of metabolic health and aging by nutrient-sensitive signaling pathways

Molecular and Cellular Endocrinology

Volumn 455, Issue , 2017, Pages 13-22

  Cummings, Nicole E ^a,b,c   Lamming, Dudley W ^a,b,c  

^a UNIVERSITY OF WISCONSIN SCHOOL OF MEDICINE AND PUBLIC HEALTH   (United States)

^b WILLIAM S MIDDLETON MEMORIAL VETERANS HOSPITAL   (United States)

^c UNIVERSITY OF WISCONSIN MADISON   (United States)

Author keywords

Aging; Branched chain amino acids; Calorie restriction; GCN2; mTOR; Protein quality; Protein restriction

Indexed keywords

AMINO ACID DERIVATIVE; BRANCHED CHAIN AMINO ACID; GUANINE NUCLEOTIDE EXCHANGE FACTOR; GUANOSINE TRIPHOSPHATASE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; CARRIER PROTEIN; CASTOR1 PROTEIN, HUMAN; EIF2AK4 PROTEIN, HUMAN; PROTEIN SERINE THREONINE KINASE; RHEB PROTEIN;

AGING; ARTICLE; CALORIC RESTRICTION; HUMAN; INSULIN RESISTANCE; LONGEVITY; MACRONUTRIENT; METABOLIC REGULATION; MOLECULAR MECHANICS; NONHUMAN; NUTRIENT CONTENT; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; PROTEIN QUALITY; REGULATORY MECHANISM; SIGNAL TRANSDUCTION; ANIMAL; CHEMISTRY; DIET; GENE EXPRESSION REGULATION; GENETICS; HEALTHY AGING; METABOLISM; PROCEDURES; PROTEIN INTAKE;

AGING; AMINO ACIDS, BRANCHED-CHAIN; ANIMALS; CALORIC RESTRICTION; CARRIER PROTEINS; DIET; DIETARY PROTEINS; GENE EXPRESSION REGULATION; HEALTHY AGING; HUMANS; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; PROTEIN-SERINE-THREONINE KINASES; RAS HOMOLOG ENRICHED IN BRAIN PROTEIN; SIGNAL TRANSDUCTION;

EID: 85007028271     PISSN: 03037207     EISSN: 18728057     Source Type: Journal    
DOI: 10.1016/j.mce.2016.11.014     Document Type: Article

References (140)

1. Arriola Apelo, S.I., Lamming, D.W., Rapamycin: an inhibitor of aging emerges from the soil of Easter island. J. Gerontol. A Biol. Sci. Med. Sci. 71 (2016), 841–849.
2. Aspnes, L.E., Lee, C.M., Weindruch, R., Chung, S.S., Roecker, E.B., Aiken, J.M., Caloric restriction reduces fiber loss and mitochondrial abnormalities in aged rat muscle. FASEB J. 11 (1997), 573–581.
3. Bar-Peled, L., Chantranupong, L., Cherniack, A.D., Chen, W.W., Ottina, K.A., Grabiner, B.C., Spear, E.D., Carter, S.L., Meyerson, M., Sabatini, D.M., A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1. Science 340 (2013), 1100–1106.
4. Bar-Peled, L., Schweitzer, L.D., Zoncu, R., Sabatini, D.M., Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell 150 (2012), 1196–1208.
5. Berrigan, D., Perkins, S.N., Haines, D.C., Hursting, S.D., Adult-onset calorie restriction and fasting delay spontaneous tumorigenesis in p53-deficient mice. Carcinogenesis 23 (2002), 817–822.
6. Blagosklonny, M.V., Once again on rapamycin-induced insulin resistance and longevity: despite of or owing to. Aging (Albany NY) 4 (2012), 350–358.
7. Blomstrand, E., Eliasson, J., Karlsson, H.K., Kohnke, R., Branched-chain amino acids activate key enzymes in protein synthesis after physical exercise. J. Nutr. 136 (2006), 269S–273S.
8. Bluher, M., Kahn, B.B., Kahn, C.R., Extended longevity in mice lacking the insulin receptor in adipose tissue. Science 299 (2003), 572–574.
9. Bokov, A.F., Garg, N., Ikeno, Y., Thakur, S., Musi, N., DeFronzo, R.A., Zhang, N., Erickson, R.C., Gelfond, J., Hubbard, G.B., et al. Does reduced IGF-1R signaling in Igf1r+/- mice alter aging?. Plos One, 6, 2011, e26891.
10. Bordone, L., Guarente, L., Calorie restriction, SIRT1 and metabolism: understanding longevity. Nat. Rev. Mol. Cell Biol. 6 (2005), 298–305.
11. Bouzakri, K., Roques, M., Gual, P., Espinosa, S., Guebre-Egziabher, F., Riou, J.-P., Laville, M., Le Marchand-Brustel, Y., Tanti, J.-F., Vidal, H., Reduced activation of Phosphatidylinositol-3 kinase and increased serine 636 phosphorylation of insulin receptor Substrate-1 in primary culture of skeletal muscle cells from patients with type 2 diabetes. Diabetes 52 (2003), 1319–1325.
12. Brosnan, J.T., Brosnan, M.E., The sulfur-containing amino acids: an overview. J. Nutr. 136 (2006), 1636S–1640S.
13. Budanov, A.V., Karin, M., p53 target genes sestrin1 and sestrin2 connect genotoxic stress and mTOR signaling. Cell 134 (2008), 451–460.
14. Chaix, A., Zarrinpar, A., Miu, P., Panda, S., Time-restricted feeding is a preventative and therapeutic intervention against diverse nutritional challenges. Cell Metab. 20 (2014), 991–1005.
15. Chantranupong, L., Scaria, S.M., Saxton, R.A., Gygi, M.P., Shen, K., Wyant, G.A., Wang, T., Harper, J.W., Gygi, S.P., Sabatini, D.M., The CASTOR proteins are arginine sensors for the mTORC1 pathway. Cell 165 (2016), 153–164.
16. Chantranupong, L., Wolfson, R.L., Orozco, J.M., Saxton, R.A., Scaria, S.M., Bar-Peled, L., Spooner, E., Isasa, M., Gygi, S.P., Sabatini, D.M., The Sestrins interact with GATOR2 to negatively regulate the amino-acid-sensing pathway upstream of mTORC1. Cell Rep. 9 (2014), 1–8.
17. Chen, J.-H., Ouyang, C., Ding, Q., Song, J., Cao, W., Mao, L., A moderate low-carbohydrate low-calorie diet improves lipid profile, insulin sensitivity and adiponectin expression in rats. Nutrients 7 (2015), 4724–4738.
18. Chotechuang, N., Azzout-Marniche, D., Bos, C., Chaumontet, C., Gausseres, N., Steiler, T., Gaudichon, C., Tome, D., mTOR, AMPK, and GCN2 coordinate the adaptation of hepatic energy metabolic pathways in response to protein intake in the rat. Am. J. Physiol. Endocrinol. Metab. 297 (2009), E1313–E1323.
19. Chung, H.Y., Kim, H.J., Kim, J.W., Yu, B.P., The inflammation hypothesis of aging. Ann. N. Y. Acad. Sci. 928 (2001), 327–335.
20. Colman, R.J., Anderson, R.M., Nonhuman primate calorie restriction. Antioxid. Redox Signal. 14 (2011), 229–239.
21. Colman, R.J., Anderson, R.M., Johnson, S.C., Kastman, E.K., Kosmatka, K.J., Beasley, T.M., Allison, D.B., Cruzen, C., Simmons, H.A., Kemnitz, J.W., et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325 (2009), 201–204.
22. Colman, R.J., Beasley, T.M., Allison, D.B., Weindruch, R., Attenuation of sarcopenia by dietary restriction in rhesus monkeys. J. Gerontol. A Biol. Sci. Med. Sci. 63 (2008), 556–559.
23. Colman, R.J., Beasley, T.M., Kemnitz, J.W., Johnson, S.C., Weindruch, R., Anderson, R.M., Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat. Commun., 5, 2014, 3557.
24. Cruzen, C., Colman, R.J., Effects of caloric restriction on cardiovascular aging in non-human primates and humans. Clin. geriatr. Med. 25 (2009), 733–743.
25. Dagon, Y., Hur, E., Zheng, B., Wellenstein, K., Cantley, L.C., Kahn, B.B., p70S6 kinase phosphorylates AMPK on serine 491 to mediate leptin's effect on food intake. Cell Metab. 16 (2012), 104–112.
26. Deerberg, F., Rapp, K.G., Kaspareit-Rittinghausen, J., Lorcher, K., The effect of food restriction by time-scheduled feeding on the development of body-weight, lifespan and incidence of spontaneous tumours and diseases in male Han:SPRD rats. Z Vers. 33 (1990), 9–17.
27. Demetriades, C., Doumpas, N., Teleman, A.A., Regulation of TORC1 in response to amino acid starvation via lysosomal recruitment of TSC2. Cell 156 (2014), 786–799.
28. Demetriades, C., Plescher, M., Teleman, A.A., Lysosomal recruitment of TSC2 is a universal response to cellular stress. Nat. Commun., 7, 2016, 10662.
29. Efeyan, A., Schweitzer, L.D., Bilate, A.M., Chang, S., Kirak, O., Lamming, D.W., Sabatini, D.M., RagA, but not RagB, is essential for embryonic development and adult mice. Dev. Cell 29 (2014), 321–329.
30. Efeyan, A., Zoncu, R., Chang, S., Gumper, I., Snitkin, H., Wolfson, R.L., Kirak, O., Sabatini, D.D., Sabatini, D.M., Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature 493 (2013), 679–683.
31. Fawal, M.A., Brandt, M., Djouder, N., MCRS1 binds and couples Rheb to amino acid-dependent mTORC1 activation. Dev. Cell 33 (2015), 67–81.
32. Fontana, L., Cummings, N.E., Arriola Apelo, S.I., Neuman, J.C., Kasza, I., Schmidt, B.A., Cava, E., Spelta, F., Tosti, V., Syed, F.A., et al. Decreased consumption of branched-chain amino acids improves metabolic health. Cell Rep. 16 (2016), 520–530.
33. Fontana, L., Klein, S., Holloszy, J.O., Effects of long-term calorie restriction and endurance exercise on glucose tolerance, insulin action, and adipokine production. Age 32 (2009), 97–108.
34. Fontana, L., Meyer, T.E., Klein, S., Holloszy, J.O., Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 6659–6663.
35. Fontana, L., Partridge, L., Promoting health and longevity through diet: from model organisms to humans. Cell 161 (2015), 106–118.
36. Fontana, L., Villareal, D.T., Das, S.K., Smith, S.R., Meydani, S.N., Pittas, A.G., Klein, S., Bhapkar, M., Rochon, J., Ravussin, E., et al. Effects of 2-year calorie restriction on circulating levels of IGF-1, IGF-binding proteins and cortisol in nonobese men and women: a randomized clinical trial. Aging Cell 15 (2016), 22–27.
37. Gallinetti, J., Harputlugil, E., Mitchell, J.R., Amino acid sensing in dietary-restriction-mediated longevity: roles of signal-transducing kinases GCN2 and TOR. Biochem. J. 449 (2013), 1–10.
38. Gandin, V., Masvidal, L., Cargnello, M., Gyenis, L., McLaughlan, S., Cai, Y., Tenkerian, C., Morita, M., Balanathan, P., Jean-Jean, O., et al. mTORC1 and CK2 coordinate ternary and eIF4F complex assembly. Nat. Commun., 7, 2016, 11127.
39. Ghosh, H.S., McBurney, M., Robbins, P.D., SIRT1 negatively regulates the mammalian target of rapamycin. Plos One, 5, 2010, e9199.
40. Goberdhan, D.C., Wilson, C., Harris, A.L., Amino acid sensing by mTORC1: intracellular transporters mark the spot. Cell Metab. 23 (2016), 580–589.
41. Graff, J., Kahn, M., Samiei, A., Gao, J., Ota, K.T., Rei, D., Tsai, L.H., A dietary regimen of caloric restriction or pharmacological activation of SIRT1 to delay the onset of neurodegeneration. J. Neurosci. 33 (2013), 8951–8960.
42. Grandison, R.C., Piper, M.D.W., Partridge, L., Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462 (2009), 1061–1064.
43. Greer, E.L., Brunet, A., Different dietary restriction regimens extend lifespan by both independent and overlapping genetic pathways in C. elegans. Aging Cell 8 (2009), 113–127.
44. Gwinn, D.M., Shackelford, D.B., Egan, D.F., Mihaylova, M.M., Mery, A., Vasquez, D.S., Turk, B.E., Shaw, R.J., AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol. Cell 30 (2008), 214–226.
45. Halagappa, V.K., Guo, Z., Pearson, M., Matsuoka, Y., Cutler, R.G., Laferla, F.M., Mattson, M.P., Intermittent fasting and caloric restriction ameliorate age-related behavioral deficits in the triple-transgenic mouse model of Alzheimer's disease. Neurobiol. Dis. 26 (2007), 212–220.
46. Harper, J.M., Leathers, C.W., Austad, S.N., Does caloric restriction extend life in wild mice?. Aging cell 5 (2006), 441–449.
47. Harputlugil, E., Hine, C., Vargas, D., Robertson, L., Manning, Brendan D., Mitchell, James R., The TSC complex is required for the benefits of dietary protein restriction on stress resistance in vivo. Cell Rep. 8 (2014), 1160–1170.
48. Hashimoto, Y., Fukuda, T., Oyabu, C., Tanaka, M., Asano, M., Yamazaki, M., Fukui, M., Impact of low-carbohydrate diet on body composition: meta-analysis of randomized controlled studies. Obes. Rev. 17 (2016), 499–509.
49. Heilbronn, L.K., Ravussin, E., Calorie restriction and aging: review of the literature and implications for studies in humans. Am. J. Clin. Nutr. 78 (2003), 361–369.
50. Hsu, P.P., Kang, S.A., Rameseder, J., Zhang, Y., Ottina, K.A., Lim, D., Peterson, T.R., Choi, Y., Gray, N.S., Yaffe, M.B., et al. The mTOR-regulated phosphoproteome reveals a mechanism of mTORC1-mediated inhibition of growth factor signaling. Science 332 (2011), 1317–1322.
51. Inoki, K., Li, Y., Zhu, T., Wu, J., Guan, K.L., TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat. Cell Biol. 4 (2002), 648–657.
52. Iwasaki, K., Gleiser, C.A., Masoro, E.J., McMahan, C.A., Seo, E.J., Yu, B.P., The influence of dietary protein source on longevity and age-related disease processes of Fischer rats. J. Gerontol. 43 (1988), B5–B12.
53. Iwasaki, K., Gleiser, C.A., Masoro, E.J., McMahan, C.A., Seo, E.J., Yu, B.P., Influence of the restriction of individual dietary components on longevity and age-related disease of Fischer rats: the fat component and the mineral component. J. Gerontol. 43 (1988), B13–B21.
54. Jang, C., Oh, S.F., Wada, S., Rowe, G.C., Liu, L., Chan, M.C., Rhee, J., Hoshino, A., Kim, B., Ibrahim, A., et al. A branched-chain amino acid metabolite drives vascular fatty acid transport and causes insulin resistance. Nat. Med. 22 (2016), 421–426.
55. Jensen, M.D., Ryan, D.H., Apovian, C.M., Ard, J.D., Comuzzie, A.G., Donato, K.A., Hu, F.B., Hubbard, V.S., Jakicic, J.M., Kushner, R.F., et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American college of cardiology/American heart association task force on practice guidelines and the obesity society. J. Am. Coll. Cardiol. 63 (2014), 2985–3023.
56. Johnson, S.C., Martin, G.M., Rabinovitch, P.S., Kaeberlein, M., Preserving youth: does rapamycin deliver?. Sci. Transl. Med., 5, 2013, 211fs240 211fs240.
57. Jung, J., Genau, H.M., Behrends, C., Amino acid-dependent mTORC1 regulation by the lysosomal membrane protein SLC38A9. Mol. Cell Biol. 35 (2015), 2479–2494.
58. Kemnitz, J.W., Calorie restriction and aging in nonhuman primates. Ilar J. 52 (2011), 66–77.
59. Kennedy, B.K., Lamming, D.W., The mechanistic target of rapamycin: the grand ConducTOR of metabolism and aging. Cell Metab. 23 (2016), 990–1003.
60. Khamzina, L., Veilleux, A., Bergeron, S., Marette, A., Increased activation of the mammalian target of rapamycin pathway in liver and skeletal muscle of obese rats: possible involvement in obesity-linked insulin resistance. Endocrinology 146 (2005), 1473–1481.
61. Kim, J.S., Ro, S.H., Kim, M., Park, H.W., Semple, I.A., Park, H., Cho, U.S., Wang, W., Guan, K.L., Karin, M., et al. Sestrin2 inhibits mTORC1 through modulation of GATOR complexes. Sci. Rep., 5, 2015, 9502.
62. Laeger, T., Henagan, T.M., Albarado, D.C., Redman, L.M., Bray, G.A., Noland, R.C., Munzberg, H., Hutson, S.M., Gettys, T.W., Schwartz, M.W., et al. FGF21 is an endocrine signal of protein restriction. J. Clin. Invest. 124 (2014), 3913–3922.
63. Lagiou, P., Sandin, S., Weiderpass, E., Lagiou, A., Mucci, L., Trichopoulos, D., Adami, H.O., Low carbohydrate-high protein diet and mortality in a cohort of Swedish women. J. Intern Med. 261 (2007), 366–374.
64. Lamming, D.W., Diminished mTOR signaling: a common mode of action for endocrine longevity factors. Springer Plus, 3, 2014, 735.
65. Lamming, D.W., Anderson, R.M., Metabolic Effects of Caloric Restriction. In eLS. 2014, John Wiley & Sons, Ltd, Chichester.
66. Lamming, D.W., Cummings, N.E., Rastelli, A.L., Gao, F., Cava, E., Bertozzi, B., Spelta, F., Pili, R., Fontana, L., Restriction of dietary protein decreases mTORC1 in tumors and somatic tissues of a tumor-bearing mouse xenograft model. Oncotarget 6 (2015), 31233–31240.
67. 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. Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335 (2012), 1638–1643.
68. Landi, F., Calvani, R., Cesari, M., Tosato, M., Martone, A.M., Bernabei, R., Onder, G., Marzetti, E., Sarcopenia as the biological substrate of physical frailty. Clin. Geriatr. Med. 31 (2015), 367–374.
69. Lee, B.C., Kaya, A., Ma, S., Kim, G., Gerashchenko, M.V., Yim, S.H., Hu, Z., Harshman, L.G., Gladyshev, V.N., Methionine restriction extends lifespan of Drosophila melanogaster under conditions of low amino-acid status. Nat. Commun., 5, 2014, 3592.
70. Lee, C.-K., Klopp, R.G., Weindruch, R., Prolla, T.A., Gene expression profile of aging and its retardation by caloric restriction. Science 285 (1999), 1390–1393.
71. Lee, J.H., Budanov, A.V., Park, E.J., Birse, R., Kim, T.E., Perkins, G.A., Ocorr, K., Ellisman, M.H., Bodmer, R., Bier, E., et al. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 327 (2010), 1223–1228.
72. Lee, J.H., Budanov, A.V., Talukdar, S., Park, E.J., Park, H.L., Park, H.W., Bandyopadhyay, G., Li, N., Aghajan, M., Jang, I., et al. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metab. 16 (2012), 311–321.
73. Lee, J.H., Cho, U.S., Karin, M., Sestrin regulation of TORC1: is Sestrin a leucine sensor?. Sci. Signal, 9, 2016, re5.
74. Lee, K.P., Simpson, S.J., Clissold, F.J., Brooks, R., Ballard, J.W., Taylor, P.W., Soran, N., Raubenheimer, D., Lifespan and reproduction in Drosophila: new insights from nutritional geometry. Proc. Natl. Acad. Sci. U. S. A. 105 (2008), 2498–2503.
75. Lees, E.K., Krol, E., Grant, L., Shearer, K., Wyse, C., Moncur, E., Bykowska, A.S., Mody, N., Gettys, T.W., Delibegovic, M., Methionine restriction restores a younger metabolic phenotype in adult mice with alterations in fibroblast growth factor 21. Aging Cell 13 (2014), 817–827.
76. Levine, M.E., Suarez, J.A., Brandhorst, S., Balasubramanian, P., Cheng, C.W., Madia, F., Fontana, L., Mirisola, M.G., Guevara-Aguirre, J., Wan, J., et al. Low protein intake is associated with a major reduction in IGF-1, cancer, and overall mortality in the 65 and younger but not older population. Cell Metab. 19 (2014), 407–417.
77. Li, F., Yin, Y., Tan, B., Kong, X., Wu, G., Leucine nutrition in animals and humans: mTOR signaling and beyond. Amino Acids 41 (2011), 1185–1193.
78. Liao, C.-Y., Rikke, B.A., Johnson, T.E., Diaz, V., Nelson, J.F., Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging cell 9 (2010), 92–95.
79. Lin, S.J., Defossez, P.A., Guarente, L., Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. Science 289 (2000), 2126–2128.
80. Longo, V.D., Mattson, M.P., Fasting: molecular mechanisms and clinical applications. Cell Metab. 19 (2014), 181–192.
81. López-Otín, C., Galluzzi, L., Freije, José M.P., Madeo, F., Kroemer, G., Metabolic control of longevity. Cell 166 (2016), 802–821.
82. Lynch, C.J., Role of leucine in the regulation of mTOR by amino acids: revelations from structure-activity studies. J. Nutr. 131 (2001), 861S–865S.
83. Lynch, C.J., Adams, S.H., Branched-chain amino acids in metabolic signalling and insulin resistance. Nature reviews. Endocrinology 10 (2014), 723–736.
84. Mair, W., Piper, M.D.W., Partridge, L., Calories do not explain extension of life span by dietary restriction in Drosophila. Plos Biol., 3, 2005, e223.
85. Masternak, M.M., Panici, J.A., Bonkowski, M.S., Hughes, L.F., Bartke, A., Insulin sensitivity as a key mediator of growth hormone actions on longevity. J. Gerontol. A Biol. Sci. Med. Sci. 64 (2009), 516–521.
86. Mattison, J.A., Roth, G.S., Beasley, T.M., Tilmont, E.M., Handy, A.M., Herbert, R.L., Longo, D.L., Allison, D.B., Young, J.E., Bryant, M., et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489 (2012), 318–321.
87. Mattison, J.A., Roth, G.S., Beasley, T.M., Tilmont, E.M., Handy, A.M., Herbert, R.L., Longo, D.L., Allison, D.B., Young, J.E., Bryant, M., et al. Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489 (2012), 318–321.
88. Mattson, M.P., Allison, D.B., Fontana, L., Harvie, M., Longo, V.D., Malaisse, W.J., Mosley, M., Notterpek, L., Ravussin, E., Scheer, F.A.J.L., et al. Meal frequency and timing in health and disease. Proc. Natl. Acad. Sci. 111 (2014), 16647–16653.
89. McCarty, M.F., Barroso-Aranda, J., Contreras, F., The low-methionine content of vegan diets may make methionine restriction feasible as a life extension strategy. Med. hypotheses 72 (2009), 125–128.
90. McCay, C.M., Crowell, M.F., Maynard, L.A., The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutr. 10 (1935), 63–79.
91. McKiernan, S.H., Colman, R.J., Aiken, E., Evans, T.D., Beasley, T.M., Aiken, J.M., Weindruch, R., Anderson, R.M., Cellular adaptation contributes to calorie restriction-induced preservation of skeletal muscle in aged rhesus monkeys. Exp. Gerontol. 47 (2012), 229–236.
92. Menon, S., Dibble, C.C., Talbott, G., Hoxhaj, G., Valvezan, A.J., Takahashi, H., Cantley, L.C., Manning, B.D., Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome. Cell 156 (2014), 771–785.
93. Mercken, E.M., Carboneau, B.A., Krzysik-Walker, S.M., de Cabo, R., Of mice and men: the benefits of caloric restriction, exercise, and mimetics. Ageing Res. Rev. 11 (2012), 390–398.
94. Mercken, E.M., Crosby, S.D., Lamming, D.W., JeBailey, L., Krzysik-Walker, S., Villareal, D.T., Capri, M., Franceschi, C., Zhang, Y., Becker, K., et al. Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell 12 (2013), 645–651.
95. Meyer, T.E., Kovács, S.J., Ehsani, A.A., Klein, S., Holloszy, J.O., Fontana, L., Long-term caloric restriction Ameliorates the decline in diastolic function in humans. J. Am. Coll. Cardiol. 47 (2006), 398–402.
96. Miller, R.A., Buehner, G., Chang, Y., Harper, J.M., Sigler, R., Smith-Wheelock, M., Methionine-deficient diet extends mouse lifespan, slows immune and lens aging, alters glucose, T4, IGF-I and insulin levels, and increases hepatocyte MIF levels and stress resistance. Aging Cell 4 (2005), 119–125.
97. Mitchell, S.J., Madrigal-Matute, J., Scheibye-Knudsen, M., Fang, E., Aon, M., Gonzalez-Reyes, J.A., Cortassa, S., Kaushik, S., Gonzalez-Freire, M., Patel, B., et al. Effects of sex, strain, and energy intake on hallmarks of aging in mice. Cell Metab. 23 (2016), 1093–1112.
98. Moberg, M., Apro, W., Ohlsson, I., Ponten, M., Villanueva, A., Ekblom, B., Blomstrand, E., Absence of leucine in an essential amino acid supplement reduces activation of mTORC1 signalling following resistance exercise in young females. Appl. physiol., Nutr. metab. = Physiol. appl., Nutr. metab. 39 (2014), 183–194.
99. Neff, F., Flores-Dominguez, D., Ryan, D.P., Horsch, M., Schroder, S., Adler, T., Afonso, L.C., Aguilar-Pimentel, J.A., Becker, L., Garrett, L., et al. Rapamycin extends murine lifespan but has limited effects on aging. J. Clin. Invest. 123 (2013), 3272–3291.
100. Newgard, C.B., An, J., Bain, J.R., Muehlbauer, M.J., Stevens, R.D., Lien, L.F., Haqq, A.M., Shah, S.H., Arlotto, M., Slentz, C.A., et al. A branched-chain amino acid-related metabolic signature that differentiates obese and lean humans and contributes to insulin resistance. Cell Metab. 9 (2009), 311–326.
101. Nojima, A., Yamashita, M., Yoshida, Y., Shimizu, I., Ichimiya, H., Kamimura, N., Kobayashi, Y., Ohta, S., Ishii, N., Minamino, T., Haploinsufficiency of akt1 prolongs the lifespan of mice. Plos One, 8, 2013, e69178.
102. Nowson, C., O'Connell, S., Protein requirements and recommendations for older people: a review. Nutrients 7 (2015), 6874–6899.
103. Orentreich, N., Matias, J.R., DeFelice, A., Zimmerman, J.A., Low methionine ingestion by rats extends life span. J. Nutr. 123 (1993), 269–274.
104. Paddon-Jones, D., Rasmussen, B.B., Dietary protein recommendations and the prevention of sarcopenia. Curr. Opin. Clin. Nutr. Metab. Care 12 (2009), 86–90.
105. Park, S.K., Kim, K., Page, G.P., Allison, D.B., Weindruch, R., Prolla, T.A., Gene expression profiling of aging in multiple mouse strains: identification of aging biomarkers and impact of dietary antioxidants. Aging Cell 8 (2009), 484–495.
106. Pearson, K.J., Baur, J.A., Lewis, K.N., Peshkin, L., Price, N.L., Labinskyy, N., Swindell, W.R., Kamara, D., Minor, R.K., Perez, E., et al. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 8 (2008), 157–168.
107. Perrone, C.E., Malloy, V.L., Orentreich, D.S., Orentreich, N., Metabolic adaptations to methionine restriction that benefit health and lifespan in rodents. Exp. Gerontol. 48 (2013), 654–660.
108. Piper, M.D., Mair, W., Partridge, L., Counting the calories: the role of specific nutrients in extension of life span by food restriction. J. Gerontol. A Biol. Sci. Med. Sci. 60 (2005), 549–555.
109. Rebsamen, M., Pochini, L., Stasyk, T., de Araujo, M.E., Galluccio, M., Kandasamy, R.K., Snijder, B., Fauster, A., Rudashevskaya, E.L., Bruckner, M., et al. SLC38A9 is a component of the lysosomal amino acid sensing machinery that controls mTORC1. Nature 519 (2015), 477–481.
110. Robertson, L.T., Trevino-Villarreal, J.H., Mejia, P., Grondin, Y., Harputlugil, E., Hine, C., Vargas, D., Zheng, H., Ozaki, C.K., Kristal, B.S., et al. Protein and calorie restriction contribute Additively to protection from renal ischemia reperfusion injury partly via leptin reduction in male mice. J. Nutr. 145 (2015), 1717–1727.
111. Rogina, B., Helfand, S.L., Sir2 mediates longevity in the fly through a pathway related to calorie restriction. Proc. Natl. Acad. Sci. U. S. A. 101 (2004), 15998–16003.
112. Sancak, Y., Bar-Peled, L., Zoncu, R., Markhard, A.L., Nada, S., Sabatini, D.M., Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141 (2010), 290–303.
113. Sancak, Y., Peterson, T.R., Shaul, Y.D., Lindquist, R.A., Thoreen, C.C., Bar-Peled, L., Sabatini, D.M., The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320 (2008), 1496–1501.
114. Sans, M.D., Tashiro, M., Vogel, N.L., Kimball, S.R., D'Alecy, L.G., Williams, J.A., Leucine activates pancreatic translational machinery in rats and mice through mTOR independently of CCK and insulin. J. Nutr. 136 (2006), 1792–1799.
115. Saxton, R.A., Knockenhauer, K.E., Wolfson, R.L., Chantranupong, L., Pacold, M.E., Wang, T., Schwartz, T.U., Sabatini, D.M., Structural basis for leucine sensing by the Sestrin2-mTORC1 pathway. Science 351 (2016), 53–58.
116. Selman, C., Tullet, J.M., Wieser, D., Irvine, E., Lingard, S.J., Choudhury, A.I., Claret, M., Al-Qassab, H., Carmignac, D., Ramadani, F., et al. Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326 (2009), 140–144.
117. She, P., Reid, T.M., Bronson, S.K., Vary, T.C., Hajnal, A., Lynch, C.J., Hutson, S.M., Disruption of BCATm in mice leads to increased energy expenditure associated with the activation of a futile protein turnover cycle. Cell Metab. 6 (2007), 181–194.
118. Sluijs, I., Beulens, J.W., van der, A.D., Spijkerman, A.M., Grobbee, D.E., van der Schouw, Y.T., Dietary intake of total, animal, and vegetable protein and risk of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-NL study. Diabetes Care 33 (2010), 43–48.
119. Sohal, R.S., Weindruch, R., Oxidative stress, caloric restriction, and aging. Science 273 (1996), 59–63 (New York, N.Y.).
120. Solon-Biet, Samantha M., McMahon, Aisling C., Ballard, J., William, O., Ruohonen, K., Wu, Lindsay E., Cogger, Victoria C., Warren, A., Huang, X., Pichaud, N., Melvin, Richard G., et al. The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in Ad libitum-fed mice. Cell Metab. 19 (2014), 418–430.
121. Solon-Biet, S.M., Mitchell, S.J., Coogan, S.C., Cogger, V.C., Gokarn, R., McMahon, A.C., Raubenheimer, D., de Cabo, R., Simpson, S.J., Le Couteur, D.G., Dietary protein to carbohydrate ratio and caloric restriction: comparing metabolic outcomes in mice. Cell Rep. 11 (2015), 1529–1534.
122. Taguchi, A., Wartschow, L.M., White, M.F., Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science 317 (2007), 369–372.
123. Tremblay, F., Brule, S., Hee Um, S., Li, Y., Masuda, K., Roden, M., Sun, X.J., Krebs, M., Polakiewicz, R.D., Thomas, G., et al. Identification of IRS-1 Ser-1101 as a target of S6K1 in nutrient- and obesity-induced insulin resistance. Proc. Natl. Acad. Sci. U. S. A. 104 (2007), 14056–14061.
124. van Norren, K., Rusli, F., van Dijk, M., Lute, C., Nagel, J., Dijk, F.J., Dwarkasing, J., Boekschoten, M.V., Luiking, Y., Witkamp, R.F., et al. Behavioural changes are a major contributing factor in the reduction of sarcopenia in caloric-restricted ageing mice. J. Cachexia Sarcopenia Muscle 6 (2015), 253–268.
125. van Wyk, H.J., Davis, R.E., Davies, J.S., A critical review of low-carbohydrate diets in people with Type 2 diabetes. Diabet. Med. 33 (2016), 148–157.
126. Walford, R.L., Mock, D., Verdery, R., MacCallum, T., Calorie restriction in biosphere 2: alterations in physiologic, hematologic, hormonal, and biochemical parameters in humans restricted for a 2-year period. J. Gerontol. A Biol. Sci. Med. Sci. 57 (2002), B211–B224.
127. Wang, R.H., Kim, H.S., Xiao, C., Xu, X., Gavrilova, O., Deng, C.X., Hepatic Sirt1 deficiency in mice impairs mTorc2/Akt signaling and results in hyperglycemia, oxidative damage, and insulin resistance. J. Clin. Invest. 121 (2011), 4477–4490.
128. Wang, S., Tsun, Z.Y., Wolfson, R.L., Shen, K., Wyant, G.A., Plovanich, M.E., Yuan, E.D., Jones, T.D., Chantranupong, L., Comb, W., et al. Metabolism. Lysosomal amino acid transporter SLC38A9 signals arginine sufficiency to mTORC1. Science 347 (2015), 188–194.
129. Weindruch, R., Kayo, T., Lee, C.-K., Prolla, T.A., Microarray profiling of gene expression in aging and its alteration by caloric restriction in mice. J. Nutr. 131 (2001), 918S–923S.
130. Weindruch, R., Walford, R.L., The Retardation of Aging and Disease by Dietary Restriction. 1988, C.C. Thomas, Springfield, Ill., U.S.A.
131. Weindruch, R., Walford, R.L., Fligiel, S., Guthrie, D., The retardation of aging in mice by dietary restriction: longevity, cancer, immunity and lifetime energy intake. J. Nutr. 116 (1986), 641–654.
132. White, P.J., Lapworth, A.L., An, J., Wang, L., McGarrah, R.W., Stevens, R.D., Ilkayeva, O., George, T., Muehlbauer, M.J., Bain, J.R., et al. Branched-chain amino acid restriction in Zucker-fatty rats improves muscle insulin sensitivity by enhancing efficiency of fatty acid oxidation and acyl-glycine export. Mol. Metab..
133. Wilkinson, J.E., Burmeister, L., Brooks, S.V., Chan, C.-C., Friedline, S., Harrison, D.E., Hejtmancik, J.F., Nadon, N., Strong, R., Wood, L.K., et al. Rapamycin slows aging in mice. Aging Cell 11 (2012), 675–682.
134. Wolfe, R.R., Miller, S.L., Miller, K.B., Optimal protein intake in the elderly. Clin. Nutr. 27 (2008), 675–684.
135. Wolfson, R.L., Chantranupong, L., Saxton, R.A., Shen, K., Scaria, S.M., Cantor, J.R., Sabatini, D.M., Sestrin2 is a leucine sensor for the mTORC1 pathway. Science 351 (2016), 43–48.
136. Wu, J.J., Liu, J., Chen, E.B., Wang, J.J., Cao, L., Narayan, N., Fergusson, M.M., Rovira II, Allen, M., Springer, D.A., et al. Increased mammalian lifespan and a segmental and tissue-specific slowing of aging after genetic reduction of mTOR expression. Cell Rep. 4 (2013), 913–920.
137. Xiao, F., Huang, Z., Li, H., Yu, J., Wang, C., Chen, S., Meng, Q., Cheng, Y., Gao, X., Li, J., et al. Leucine deprivation increases hepatic insulin sensitivity via GCN2/mTOR/S6K1 and AMPK pathways. Diabetes 60 (2011), 746–756.
138. Xiao, F., Yu, J., Guo, Y., Deng, J., Li, K., Du, Y., Chen, S., Zhu, J., Sheng, H., Guo, F., Effects of individual branched-chain amino acids deprivation on insulin sensitivity and glucose metabolism in mice. Metabolism 63 (2014), 841–850.
139. Ye, J., Palm, W., Peng, M., King, B., Lindsten, T., Li, M.O., Koumenis, C., Thompson, C.B., GCN2 sustains mTORC1 suppression upon amino acid deprivation by inducing Sestrin2. Genes Dev. 29 (2015), 2331–2336.
140. Zhang, Y., Bokov, A., Gelfond, J., Soto, V., Ikeno, Y., Hubbard, G., Diaz, V., Sloane, L., Maslin, K., Treaster, S., et al. Rapamycin extends life and health in C57BL/6 mice. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 69A (2014), 119–130.