The impact of low-protein high-carbohydrate diets on aging and lifespan

Cellular and Molecular Life Sciences

Volumn 73, Issue 6, 2016, Pages 1237-1252

  Le Couteur, David G ^a,b   Solon Biet, Samantha ^a,b   Cogger, Victoria C ^a,b   Mitchell, Sarah J ^c   Senior, Alistair ^a   De Cabo, Rafael ^a   Raubenheimer, David ^a   Simpson, Stephen J ^a  

^a UNIVERSITY OF SYDNEY   (Australia)

^b Department of Microbiology and Infectious Diseases   (Australia)

^c NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Ageing; Aging; Caloric restriction; CPC diet; Dietary carbohydrate; Dietary protein; Geometric Framework

Indexed keywords

AGING; BODY FAT; CALORIC RESTRICTION; COLD; COMPENSATORY FEEDING; DIET; ENVIRONMENTAL TEMPERATURE; EXERCISE; FOOD INTAKE; GEOMETRIC FRAMEWORK; HUMAN; INSECT; LIFE EXTENSION; LIFESPAN; LOW PROTEIN HIGH CARBOHYDRATE DIET; METHODOLOGY; NONHUMAN; NUTRITION; PHYSICAL ACTIVITY; PROTEIN LEVERAGE; REPRODUCTIVE FITNESS; REVIEW; WEIGHT REDUCTION; ANIMAL; CARBOHYDRATE DIET; LONGEVITY; METABOLISM; PROCEDURES; PROTEIN INTAKE; PROTEIN RESTRICTION;

CARBOHYDRATE DIET; PROTEIN INTAKE;

AGING; ANIMALS; CALORIC RESTRICTION; DIET, PROTEIN-RESTRICTED; DIETARY CARBOHYDRATES; DIETARY PROTEINS; HUMANS; LONGEVITY;

EID: 84958771871     PISSN: 1420682X     EISSN: 14209071     Source Type: Journal    
DOI: 10.1007/s00018-015-2120-y     Document Type: Review

References (129)

1. Schafer D (2005) Aging, longevity, and diet: Historical remarks on calorie intake reduction. Gerontology 51:126-130
2. Howell TH (1987) The art of living long by Luigi Cornaro. Age Ageing 16:194-195
3. McCay C, Crowell M, Maynard L (1935) The effect of retarded growth upon the length of life and upon ultimate size. J Nutr 10:63-79
4. Mercken EM, Carboneau BA, Krzysik-Walker SM, de Cabo R (2012) Of mice and men: The benefits of caloric restriction, exercise, and mimetics. Ageing Res Rev 11:390-398
5. Everitt AV, Rattan SI, Le Couteur DG, de Cabo R (2010) Calorie restriction, aging and longevity. Springer Press, New York
6. de Cabo R, Le Couteur DG (2015) The biology of ageing. In: Kasper DL, Fauci AS, Hauser SL, Longo DL, Jameson JL, Loscalzo J (eds) Harrisons principles of internal medicine, 19th edn. McGraw Hill Education, New York, p 94e
7. Masoro EJ (2005) Overview of caloric restriction and ageing. Mech Ageing Dev 126:913-922
8. Fontana L, Partridge L, Longo VD (2010) Extending healthy life span-from yeast to humans. Science 328:321-326
9. Rizza W, Veronese N, Fontana L (2014) What are the roles of calorie restriction and diet quality in promoting healthy longevity? Ageing Res Rev 13:38-45
10. Ravussin E, Redman LM, Rochon J, Das SK, Fontana L, Kraus WE, Romashkan S, Williamson DA, Meydani SN, Villareal DT, Smith SR, Stein RI, Scott TM, Stewart TM, Saltzman E, Klein S, Bhapkar M, Martin CK, Gilhooly CH, Holloszy JO, Hadley EC, Roberts SB, Group CS (2015) A 2-year randomized controlled trial of human caloric restriction: Feasibility and effects on predictors of health span and longevity. J Gerontol A Biol Sci Med Sci 70:1097-1104
11. Guarente L, Picard F (2005) Calorie restriction-the SIR2 connection. Cell 120:473-482
12. Solon-Biet SM, Mitchell SJ, de Cabo R, Raubenheimer D, Le Couteur DG, Simpson SJ (2015) Macronutrients and caloric intake in health and longevity. J Endocrinol 226:R17-R28
13. Le Couteur DG, McLachlan AJ, Quinn RJ, Simpson SJ, de Cabo R (2012) Aging biology and novel targets for drug discovery. J Gerontol A Biol Sci Med Sci 67:169-174
14. Simpson SJ, Le Couteur DG, Raubenheimer D (2015) Putting the balance back in diet. Cell 161:18-23
15. Minor RK, Allard JS, Younts CM, Ward TM, de Cabo R (2010) Dietary interventions to extend life span and health span based on calorie restriction. J Gerontol A Biol Sci Med Sci 65:695-703
16. Simpson SJ, Raubenheimer D (2005) Obesity: The protein leverage hypothesis. Obes Rev 6:133-142
17. Simpson SJ, Raubenheimer D (2012) The nature of nutrition. A unifying framework form animal adaption to human obesity. Princeton University Press, Princeton
18. Le Couteur DG, Wilder SM, de Cabo R, Simpson SJ (2014) The evolution of research on ageing and nutrition. J Gerontol A Biol Sci Med Sci 69:1-2
19. Simpson SJ, Raubenheimer D (2007) Caloric restriction and aging revisited: The need for a geometric analysis of the nutritional bases of aging. J Gerontol A Biol Sci Med Sci 62:707-713
20. Simpson SJ, Raubenheimer D (2014) Perspective: Tricks of the trade. Nature 508:S66
21. Lee KP, Simpson SJ, Clissold FJ, Brooks R, Ballard JW, Taylor PW, Soran N, Raubenheimer D (2008) Lifespan and reproduction in Drosophila: New insights from nutritional geometry. Proc Natl Acad Sci USA 105:2498-2503
22. Skorupa DA, Dervisefendic A, Zwiener J, Pletcher SD (2008) Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster. Aging Cell 7:478-490
23. Jensen K, McClure C, Priest NK, Hunt J (2015) Sex-specific effects of protein and carbohydrate intake on reproduction but not lifespan in Drosophila melanogaster. Aging Cell 14:605-615
24. Fanson BG, Taylor PW (2012) Protein:carbohydrate ratios explain life span patterns found in Queensland fruit fly on diets varying in yeast:sugar ratios. Age (Dordr) 34:1361-1368
25. Fanson BG, Weldon CW, Perez-Staples D, Simpson SJ, Taylor PW (2009) Nutrients, not caloric restriction, extend lifespan in Queensland fruit flies (Bactrocera tryoni). Aging Cell 8:514-523
26. Harrison SJ, Raubenheimer D, Simpson SJ, Godin JG, Bertram SM (2014) Towards a synthesis of frameworks in nutritional ecology: Interacting effects of protein, carbohydrate and phosphorus on field cricket fitness. Proc Biol Sci 281(1792). doi: 10.1098/rspb.2014.0539
27. Solon-Biet S, McMahon A, Ballard JWO, Ruohonen K, Wu L, Cogger V, Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, Khalil M, Turner N, Cooney G, Sinclair D, Raubenheimer D, Le Couteur D, Simpson S (2014) The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging and longevity in ad libitum-fed mice. Cell Metab 19:418-430
28. Holliday R (2006) Food, fertility and longevity. Biogerontology 7:139-141
29. McCay CM, Bing FC, Dilley WE (1928) Factor H in the nutrition of trout. Science 67:249-250
30. Maklakov AA, Simpson SJ, Zajitschek F, Hall MD, Dessmann J, Clissold F, Raubenheimer D, Bonduriansky R, Brooks RC (2008) Sex-specific fitness effects of nutrient intake on reproduction and lifespan. Curr Biol 18:1062-1066
31. Dussutour A, Simpson SJ (2012) Ant workers die young and colonies collapse when fed a high-protein diet. Proc Biol Sci 279:2402-2408
32. Paoli PP, Donley D, Stabler D, Saseendranath A, Nicolson SW, Simpson SJ, Wright GA (2014) Nutritional balance of essential amino acids and carbohydrates of the adult worker honeybee depends on age. Amino Acids 46:1449-1458
33. Stabler D, Paoli PP, Nicolson SW, Wright GA (2015) Nutrient balancing of the adult worker bumblebee (Bombus terrestris) depends on the dietary source of essential amino acids. J Exp Biol 218:793-802
34. Grandison RC, Piper MD, Partridge L (2009) Amino-acid imbalance explains extension of lifespan by dietary restriction in Drosophila. Nature 462:1061-1064
35. Dick KB, Ross CR, Yampolsky LY (2011) Genetic variation of dietary restriction and the effects of nutrient-free water and amino acid supplements on lifespan and fecundity of Drosophila. Genet Res (Camb) 93:265-273
36. Emran S, Yang M, He X, Zandveld J, Piper MD (2014) Target of rapamycin signalling mediates the lifespan-extending effects of dietary restriction by essential amino acid alteration. Aging (Albany NY) 6:390-398
37. Zajitschek F, Zajitschek SR, Friberg U, Maklakov AA (2013) Interactive effects of sex, social environment, dietary restriction, and methionine on survival and reproduction in fruit flies. Age (Dordr) 35:1193-1204
38. Carey JR, Harshman LG, Liedo P, Muller HG, Wang JL, Zhang Z (2008) Longevity-fertility trade-offs in the tephritid fruit fly, Anastrepha ludens, across dietary-restriction gradients. Aging Cell 7:470-477
39. Zou S, Carey JR, Liedo P, Ingram DK, Yu B, Ghaedian R (2010) Prolongevity effects of an oregano and cranberry extract are diet dependent in the Mexican fruit fly (Anastrepha ludens). J Gerontol A Biol Sci Med Sci 65:41-50
40. Wang C, Wheeler CT, Alberico T, Sun X, Seeberger J, Laslo M, Spangler E, Kern B, de Cabo R, Zou S (2011) The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster. Age (Dordr) 35:69-81
41. Baur JA, Pearson KJ, Price NL, Jamieson HA, Lerin C, Kalra A, Prabhu VV, Allard JS, Lopez-Lluch G, Lewis K, Pistell PJ, Poosala S, Becker KG, Boss O, Gwinn D, Wang M, Ramaswamy S, Fishbein KW, Spencer RG, Lakatta EG, Le Couteur D, Shaw RJ, Navas P, Puigserver P, Ingram DK, de Cabo R, Sinclair DA (2006) Resveratrol improves health and survival of mice on a high-calorie diet. Nature 444:337-342
42. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R (2008) Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab 8:157-168
43. Min KJ, Tatar M (2006) Restriction of amino acids extends lifespan in Drosophila melanogaster. Mech Ageing Dev 127:643-646
44. Lee KP (2015) Dietary protein:carbohydrate balance is a critical modulator of lifespan and reproduction in Drosophila melanogaster: A test using a chemically defined diet. J Insect Physiol 75:12-19
45. Ja WW, Carvalho GB, Zid BM, Mak EM, Brummel T, Benzer S (2009) Water-and nutrient-dependent effects of dietary restriction on Drosophila lifespan. Proc Natl Acad Sci USA 106:18633-18637
46. Adler MI, Bonduriansky R (2014) Why do the well-fed appear to die young? A new evolutionary hypothesis for the effect of dietary restriction on lifespan. BioEssays 36:439-450
47. Le Couteur DG, Tay SS, Solon-Biet S, Bertolino P, McMahon AC, Cogger VC, Colakoglu F, Warren A, Holmes AJ, Pichaud N, Horan M, Correa C, Melvin RG, Turner N, Ballard JW, Ruohonen K, Raubenheimer D, Simpson SJ (2014) The influence of macronutrients on splanchnic and hepatic lymphocytes in aging mice. J Gerontol A Biol Sci Med Sci 70:1499-1507
48. Solon-Biet SM, Walters KA, Simanainen UK, McMahon AC, Ruohonen K, Ballard JW, Raubenheimer D, Handelsman DJ, Le Couteur DG, Simpson SJ (2015) Macronutrient balance, reproductive function, and lifespan in aging mice. Proc Natl Acad Sci USA 112:3481-3486
49. Nakagawa I, Masana Y (1971) Effect of protein nutrition on growth and life span in the rat. J Nutr 101:613-620
50. Ross MH, Bras G (1973) Influence of protein under-and overnutrition on spontaneous tumor prevalence in the rat. J Nutr 103:944-963
51. Davis TA, Bales CW, Beauchene RE (1983) Differential effects of dietary caloric and protein restriction in the aging rat. Exp Gerontol 18:427-435
52. Leto S, Kokkonen GC, Barrows CH Jr (1976) Dietary protein, life-span, and biochemical variables in female mice. J Gerontol 31:144-148
53. Leto S, Kokkonen GC, Barrows CH (1976) Dietary protein life-span, and physiological variables in female mice. J Gerontol 31:149-154
54. Goodrick CL (1978) Body weight increment and length of life: The effect of genetic constitution and dietary protein. J Gerontol 33:184-190
55. Slonaker JR (1931) The effect of different per cents of protein in the diet I Growth. Am J Physiol 96:547-556
56. Horakova M, Deyl Z, Hausmann J, Macek K (1988) The effect of low protein-high dextrin diet and subsequent food restriction upon life prolongation in Fischer 344 male rats. Mech Ageing Dev 45:1-7
57. Yu BP, Masoro EJ, McMahan CA (1985) Nutritional influences on aging of Fischer 344 rats: I. Physical, metabolic, and longevity characteristics. J Gerontol 40:657-670
58. Masoro EJ, Iwasaki K, Gleiser CA, McMahan CA, Seo EJ, Yu BP (1989) Dietary modulation of the progression of nephropathy in aging rats: An evaluation of the importance of protein. Am J Clin Nutr 49:1217-1227
59. Nakagawa S, Lagisz M, Hector KL, Spencer HG (2012) Comparative and meta-analytic insights into life-extension via dietary restriction. Aging Cell 11:401-409
60. De Marte ML, Enesco HE (1986) Influence of low tryptophan diet on survival and organ growth in mice. Mech Ageing Dev 36:161-171
61. Zimmerman JA, Malloy V, Krajcik R, Orentreich N (2003) Nutritional control of aging. Exp Gerontol 38:47-52
62. Lopez-Torres M, Barja G (2008) Lowered methionine ingestion as responsible for the decrease in rodent mitochondrial oxidative stress in protein and dietary restriction possible implications for humans. Biochim Biophys Acta 1780:1337-1347
63. Pamplona R, Barja G (2006) Mitochondrial oxidative stress, aging and caloric restriction: The protein and methionine connection. Biochim Biophys Acta 1757:496-508
64. Iwasaki K, Gleiser CA, Masoro EJ, McMahan CA, Seo EJ, Yu BP (1988) 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:B13-B21
65. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, Nadon NL, Wilkinson JE, Frenkel K, Carter CS, Pahor M, Javors MA, Fernandez E, Miller RA (2009) Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 460:392-395
66. Mirzaei H, Suarez JA, Longo VD (2014) Protein and amino acid restriction, aging and disease: From yeast to humans. Trends Endocrinol Metab 25:558-566
67. Baur JA, Ungvari Z, Minor RK, Le Couteur DG, de Cabo R (2012) Are sirtuins proper targets for improving healthspan and lifespan? Nat Rev Drug Discov 11:443-461
68. Mercken EM, Mitchell SJ, Martin-Montalvo A, Minor RK, Almeida M, Gomes AP, Scheibye-Knudsen M, Palacios HH, Licata JJ, Zhang YQ, Becker KG, Khraiwesh H, Gonzalez-Reyes JA, Villalba JM, Baur JA, Elliott P, Westphal C, Vlasuk GP, Ellis JL, Sinclair DA, Bernier M, de Cabo R (2014) SRT2104 extends survival of male mice on a standard diet and preserves bone and muscle mass. Aging Cell 13:787-796
69. Fung TT, van Dam RM, Hankinson SE, Stampfer M, Willett WC, Hu FB (2010) Low-carbohydrate diets and all-cause and cause-specific mortality: Two cohort studies. Ann Intern Med 153:289-298
70. Blouet C, Mariotti F, Azzout-Marniche D, Bos C, Mathe V, Tome D, Huneau JF (2006) The reduced energy intake of rats fed a high-protein low-carbohydrate diet explains the lower fat deposition, but macronutrient substitution accounts for the improved glycemic control. J Nutr 136:1849-1854
71. Foo SY, Heller ER, Wykrzykowska J, Sullivan CJ, Manning-Tobin JJ, Moore KJ, Gerszten RE, Rosenzweig A (2009) Vascular effects of a low-carbohydrate high-protein diet. Proc Natl Acad Sci USA 106:15418-15423
72. Solon-Biet SM, Mitchell SJ, Coogan SC, Cogger VC, Gokarn R, McMahon AC, Raubenheimer D, de Cabo R, Simpson SJ, Le Couteur DG (2015) Dietary protein to carbohydrate ratio and caloric restriction: Comparing metabolic outcomes in mice. Cell Rep 11:1529-1534
73. Mitchell SE, Delville C, Konstantopedos P, Derous D, Green CL, Chen L, Han JD, Wang Y, Promislow DE, Douglas A, Lusseau D, Speakman JR (2015) The effects of graded levels of calorie restriction: III. Impact of short term calorie and protein restriction on mean daily body temperature and torpor use in the C57BL/6 mouse. Oncotarget 6:18314-18337
74. Mitchell SE, Delville C, Konstantopedos P, Hurst J, Derous D, Green C, Chen L, Han JJ, Wang Y, Promislow DE, Lusseau D, Douglas A, Speakman JR (2015) The effects of graded levels of calorie restriction: II. Impact of short term calorie and protein restriction on circulating hormone levels, glucose homeostasis and oxidative stress in male C57BL/6 mice. Oncotarget 6:23213-23237
75. Mitchell SE, Tang Z, Kerbois C, Delville C, Konstantopedos P, Bruel A, Derous D, Green C, Aspden RM, Goodyear SR, Chen L, Han JJ, Wang Y, Promislow DE, Lusseau D, Douglas A, Speakman JR (2015) The effects of graded levels of calorie restriction: I. impact of short term calorie and protein restriction on body composition in the C57BL/6 mouse. Oncotarget 6:15902-15930
76. Huang X, Hancock DP, Gosby AK, McMahon AC, Solon SM, Le Couteur DG, Conigrave AD, Raubenheimer D, Simpson SJ (2013) Effects of dietary protein to carbohydrate balance on energy intake, fat storage, and heat production in mice. Obesity (Silver Spring) 21:85-92
77. Noto H, Goto A, Tsujimoto T, Noda M (2013) Low-carbohydrate diets and all-cause mortality: A systematic review and meta-analysis of observational studies. PLoS One 8:e55030
78. Naude CE, Schoonees A, Senekal M, Young T, Garner P, Volmink J (2014) Low carbohydrate versus isoenergetic balanced diets for reducing weight and cardiovascular risk: A systematic review and meta-analysis. PLoS One 9:e100652
79. Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, Kraemer HC, King AC (2007) Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: The A TO Z Weight Loss Study: A randomized trial. JAMA 297:969-977
80. Hession M, Rolland C, Kulkarni U, Wise A, Broom J (2009) Systematic review of randomized controlled trials of low-carbohydrate vs. low-fat/low-calorie diets in the management of obesity and its comorbidities. Obes Rev 10:36-50
81. Ajala O, English P, Pinkney J (2013) Systematic review and meta-analysis of different dietary approaches to the management of type 2 diabetes. Am J Clin Nutr 97:505-516
82. Pedersen AN, Kondrup J, Borsheim E (2013) Health effects of protein intake in healthy adults: A systematic literature review. Food Nutr Res. doi: 10.3402/fnr.v3457i3400.21245
83. Lagiou P, Sandin S, Weiderpass E, Lagiou A, Mucci L, Trichopoulos D, Adami HO (2007) Low carbohydrate-high protein diet and mortality in a cohort of Swedish women. J Intern Med 261:366-374
84. Trichopoulou A, Psaltopoulou T, Orfanos P, Hsieh CC, Trichopoulos D (2007) Low-carbohydrate-high-protein diet and long-term survival in a general population cohort. Eur J Clin Nutr 61:575-581
85. Sjogren P, Becker W, Warensjo E, Olsson E, Byberg L, Gustafsson IB, Karlstrom B, Cederholm T (2010) Mediterranean and carbohydrate-restricted diets and mortality among elderly men: A cohort study in Sweden. Am J Clin Nutr 92:967-974
86. Nilsson LM, Winkvist A, Eliasson M, Jansson JH, Hallmans G, Johansson I, Lindahl B, Lenner P, Van Guelpen B (2012) Low-carbohydrate, high-protein score and mortality in a northern Swedish population-based cohort. Eur J Clin Nutr 66:694-700
87. Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H (2008) Carbohydrate intake and incidence of type 2 diabetes in the European Prospective Investigation into Cancer and Nutrition (EPIC)-Potsdam Study. Br J Nutr 99:1107-1116
88. Sluijs I, Beulens JW, van der AD, Spijkerman AM, Grobbee DE, van der Schouw YT (2010) 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 33:43-48
89. Lagiou P, Sandin S, Lof M, Trichopoulos D, Adami HO, Weiderpass E (2012) Low carbohydrate-high protein diet and incidence of cardiovascular diseases in Swedish women: Prospective cohort study. BMJ 344:e4026
90. Simpson SJ, Batley R, Raubenheimer D (2003) Geometric analysis of macronutrient intake in humans: The power of protein? Appetite 41:123-140
91. Wildman RP (2009) Healthy obesity. Curr Opin Clin Nutr Metab Care 12:438-443
92. Liao CY, Rikke BA, Johnson TE, Gelfond JA, Diaz V, Nelson JF (2011) Fat maintenance is a predictor of the murine lifespan response to dietary restriction. Aging Cell 10:629-639
93. Harrison DE, Archer JR, Astle CM (1984) Effects of food restriction on aging: Separation of food intake and adiposity. Proc Natl Acad Sci USA 81:1835-1838
94. Lopez-Lluch G, Irusta PM, Navas P, de Cabo R (2008) Mitochondrial biogenesis and healthy aging. Exp Gerontol 43:813-819
95. Gonzalez-Freire M, de Cabo R, Bernier M, Sollott SJ, Fabbri E, Navas P, Ferrucci L (2015) Reconsidering the role of mitochondria in aging. J Gerontol A Biol Sci Med Sci 70:1334-1342
96. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G (2013) The hallmarks of aging. Cell 153:1194-1217
97. Miquel J, Economos AC, Fleming J, Johnson JE Jr (1980) Mitochondrial role in cell aging. Exp Gerontol 15:575-591
98. Ristow M, Zarse K (2010) How increased oxidative stress promotes longevity and metabolic health: The concept of mitochondrial hormesis (mitohormesis). Exp Gerontol 45:410-418
99. Scialo F, Sriram A, Naudi A, Ayala V, Jove M, Pamplona R, Sanz A (2015) Target of rapamycin activation predicts lifespan in fruit flies. Cell Cycle 14:2949-2958
100. Wei Y, Zhang YJ, Cai Y, Xu MH (2015) The role of mitochondria in mTOR-regulated longevity. Biol Rev Camb Philos Soc 90:167-181
101. Guarente L (2007) Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol 72:483-488
102. Rambold AS, Kostelecky B, Lippincott-Schwartz J (2011) Fuse or die: Shaping mitochondrial fate during starvation. Commun Integr Biol 4:752-754
103. Solon-Biet SM, McMahon AC, Ballard JW, Ruohonen K, Wu LE, Cogger VC, Warren A, Huang X, Pichaud N, Melvin RG, Gokarn R, Khalil M, Turner N, Cooney GJ, Sinclair DA, Raubenheimer D, Le Couteur DG, Simpson SJ (2014) The ratio of macronutrients, not caloric intake, dictates cardiometabolic health, aging, and longevity in ad libitum-fed mice. Cell Metab 19:418-430
104. Holloszy JO (1997) Mortality rate and longevity of food-restricted exercising male rats: A reevaluation. J Appl Physiol (1985) 82:399-403
105. Chen D, Steele AD, Lindquist S, Guarente L (2005) Increase in activity during calorie restriction requires Sirt1. Science 310:1641
106. Conti B (2008) Considerations on temperature, longevity and aging. Cell Mol Life Sci 65:1626-1630
107. Vaanholt LM, Daan S, Schubert KA, Visser GH (2009) Metabolism and aging: Effects of cold exposure on metabolic rate, body composition, and longevity in mice. Physiol Biochem Zool 82:314-324
108. Landsberg L (2012) Core temperature: A forgotten variable in energy expenditure and obesity? Obes Rev 13(Suppl 2):97-104
109. Simpson SJ, Raubenheimer D (1997) Geometric analysis of macronutrient selection in the rat. Appetite 28:201-213
110. Slocum N, Durrant JR, Bailey D, Yoon L, Jordan H, Barton J, Brown RH, Clifton L, Milliken T, Harrington W, Kimbrough C, Faber CA, Cariello N, Elangbam CS (2013) Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment. Exp Toxicol Pathol 65:549-557
111. Busiello RA, Savarese S, Lombardi A (2015) Mitochondrial uncoupling proteins and energy metabolism. Front Physiol 6:36
112. Caldeira da Silva CC, Cerqueira FM, Barbosa LF, Medeiros MH, Kowaltowski AJ (2008) Mild mitochondrial uncoupling in mice affects energy metabolism, redox balance and longevity. Aging Cell 7:552-560
113. Mookerjee SA, Divakaruni AS, Jastroch M, Brand MD (2010) Mitochondrial uncoupling and lifespan. Mech Ageing Dev 131:463-472
114. Gates AC, Bernal-Mizrachi C, Chinault SL, Feng C, Schneider JG, Coleman T, Malone JP, Townsend RR, Chakravarthy MV, Semenkovich CF (2007) Respiratory uncoupling in skeletal muscle delays death and diminishes age-related disease. Cell Metab 6:497-505
115. Neufer PD, Bamman MM, Muoio DM, Bouchard C, Cooper DM, Goodpaster BH, Booth FW, Kohrt WM, Gerszten RE, Mattson MP, Hepple RT, Kraus WE, Reid MB, Bodine SC, Jakicic JM, Fleg JL, Williams JP, Joseph L, Evans M, Maruvada P, Rodgers M, Roary M, Boyce AT, Drugan JK, Koenig JI, Ingraham RH, Krotoski D, Garcia-Cazarin M, McGowan JA, Laughlin MR (2015) Understanding the cellular and molecular mechanisms of physical activity-induced health benefits. Cell Metab 22:4-11
116. Broskey NT, Greggio C, Boss A, Boutant M, Dwyer A, Schlueter L, Hans D, Gremion G, Kreis R, Boesch C, Canto C, Amati F (2014) Skeletal muscle mitochondria in the elderly: Effects of physical fitness and exercise training. J Clin Endocrinol Metab 99:1852-1861
117. Van Herrewege J (1974) Nutritional requirements of adult Drosophila melanogaster: The influence of the casein concentration on the duration of life. Exp Gerontol 9:191-198
118. Mair W, Piper MD, Partridge L (2005) Calories do not explain extension of life span by dietary restriction in Drosophila. PLoS Biol 3:e223
119. Lushchak OV, Gospodaryov DV, Rovenko BM, Glovyak AD, Yurkevych IS, Klyuba VP, Shcherbij MV, Lushchak VI (2012) Balance between macronutrients affects life span and functional senescence in fruit fly Drosophila melanogaster. J Gerontol A Biol Sci Med Sci 67:118-125
120. Bruce KD, Hoxha S, Carvalho GB, Yamada R, Wang HD, Karayan P, He S, Brummel T, Kapahi P, Ja WW (2013) High carbohydrate-low protein consumption maximizes Drosophila lifespan. Exp Gerontol 48:1129-1135
121. Zhu CT, Ingelmo P, Rand DM (2014) GxGxE for lifespan in Drosophila: Mitochondrial, nuclear, and dietary interactions that modify longevity. PLoS Genet 10:e1004354
122. Piper MD, Blanc E, Leitao-Goncalves R, Yang M, He X, Linford NJ, Hoddinott MP, Hopfen C, Soultoukis GA, Niemeyer C, Kerr F, Pletcher SD, Ribeiro C, Partridge L (2014) A holidic medium for Drosophila melanogaster. Nat Methods 11:100-105
123. Liedo P, Carey JR, Ingram DK, Zou S (2012) The interplay among dietary fat, sugar, protein and acai (Euterpe oleracea Mart.) pulp in modulating lifespan and reproduction in a Tephritid fruit fly. Exp Gerontol 47:536-539
124. Pirk CW, Boodhoo C, Human H, Nicolson SW (2009) The importance of portein type and protein to carbohydrate ratio for survival and ovarian activation of caged honeybees (Apis mellifera scutella). Apidologie 41:62-72
125. Paoli PP, Wakeling LA, Wright GA, Ford D (2014) The dietary proportion of essential amino acids and Sir2 influence lifespan in the honeybee. Age (Dordr) 36:9649
126. Preuss HG (1997) Effects of diets containing different proportions of macronutrients on longevity of normotensive Wistar rats. Geriatr Nephrol Urol 7:81-86
127. Lopez-Lluch G, Hunt N, Jones B, Zhu M, Jamieson H, Hilmer S, Cascajo MV, Allard J, Ingram DK, Navas P, de Cabo R (2006) Calorie restriction induces mitochondrial biogenesis and bioenergetic efficiency. Proc Natl Acad Sci USA 103:1768-1773
128. Bevilacqua L, Ramsey JJ, Hagopian K, Weindruch R, Harper ME (2005) Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria. Am J Physiol Endocrinol Metab 289:E429-E438
129. Slonaker JR (1931) The effect of different per cents of protein in the diet III Intake and expenditure of energy. Am J Physiol 97:15-21