Calorie restriction in humans: An update

Ageing Research Reviews

Volumn 39, Issue , 2017, Pages 36-45

  Most, Jasper ^a   Tosti, Valeria ^b   Redman, Leanne M ^a   Fontana, Luigi ^b,c,d  

^a PENNINGTON BIOMEDICAL RESEARCH CENTER   (United States)

^b WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^c UNIVERSITY OF BRESCIA   (Italy)

^d CEINGE BIOTECNOLOGIE AVANZATE   (Italy)

Author keywords

Age associated diseases; Aging; CALERIE; Calorie restriction; Energy metabolism; Metabolic adaptation

Indexed keywords

AGED; BONE DENSITY; BONE METABOLISM; CALORIC RESTRICTION; CARDIOMETABOLIC RISK; ENERGY METABOLISM; HUMAN; MALNUTRITION; MENTAL CAPACITY; PHYSICAL ACTIVITY; PSYCHOLOGICAL ASPECT; RANDOMIZED CONTROLLED TRIAL (TOPIC); REVIEW; STARVATION; VERY ELDERLY; ADAPTATION; AGING; CALORIC INTAKE; CARDIOVASCULAR DISEASE; CHRONIC DISEASE; HEALTHY AGING; LONGEVITY; METABOLISM; NEOPLASM; NON INSULIN DEPENDENT DIABETES MELLITUS; NUTRITIONAL STATUS; OBSERVATIONAL STUDY; PHYSIOLOGY; RISK FACTOR;

ADAPTATION, PHYSIOLOGICAL; AGING; CALORIC RESTRICTION; CARDIOVASCULAR DISEASES; CHRONIC DISEASE; DIABETES MELLITUS, TYPE 2; ENERGY INTAKE; ENERGY METABOLISM; HEALTHY AGING; HUMANS; LONGEVITY; NEOPLASMS; NUTRITIONAL STATUS; OBSERVATIONAL STUDIES AS TOPIC; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RISK FACTORS;

EID: 84994071287     PISSN: 15681637     EISSN: 18729649     Source Type: Journal    
DOI: 10.1016/j.arr.2016.08.005     Document Type: Review

References (115)

1. Ahmed, T., Das, S.K., Golden, J.K., Saltzman, E., Roberts, S.B., Meydani, S.N., Calorie restriction enhances T-cell-mediated immune response in adult overweight men and women. J. Gerontol. Ser. A: Biol. Sci. Med. Sci. 64 (2009), 1107–1113.
2. Anand, S.S., Yi, Q., Gerstein, H., Lonn, E., Jacobs, R., Vuksan, V., Teo, K., Davis, B., Montague, P., Yusuf, S., Relationship of metabolic syndrome and fibrinolytic dysfunction to cardiovascular disease. Circulation 108 (2003), 420–425.
3. Anderson, K.M., Wilson, P.W., Odell, P.M., Kannel, W.B., An updated coronary risk profile: a statement for health professionals. Circulation 83 (1991), 356–362.
4. Bureau of Agricultural Economics, U.S, U.S. Dept. of Agriculture, B.o.A.E, (eds.) Supplement for 1949 to Consumption of Food in the United States, 1909–48, 1950, Miscellaneous publication (United States. Dept. of Agriculture), Washington, D.C (p. 52).
5. Cangemi, R., Friedmann, A.J., Holloszy, J.O., Fontana, L., Long-term effects of calorie restriction on serum sex-hormone concentrations in men. Aging Cell 9 (2010), 236–242.
6. Cava, E., Fontana, L., Will calorie restriction work in humans?. Aging 5 (2013), 507–514.
7. Civitarese, A.E., Carling, S., Heilbronn, L.K., Hulver, M.H., Ukropcova, B., Deutsch, W.A., Smith, S.R., Ravussin, E., Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS Med., 4, 2007, e76.
8. 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., Weindruch, R., Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 325 (2009), 201–204.
9. 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.
10. Das, S.K., Gilhooly, C.H., Golden, J.K., Pittas, A.G., Fuss, P.J., Cheatham, R.A., Tyler, S., Tsay, M., McCrory, M.A., Lichtenstein, A.H., Dallal, G.E., Dutta, C., Bhapkar, M.V., Delany, J.P., Saltzman, E., Roberts, S.B., Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial. Am. J. Clin. Nutr. 85 (2007), 1023–1030.
11. Das, S.K., Gilhooly, C.H., Golden, J.K., Pittas, A.G., Fuss, P.J., Cheatham, R.A., Tyler, S., Tsay, M., McCrory, M.A., Lichtenstein, A.H., Dallal, G.E., Dutta, C., Bhapkar, M.V., Delany, J.P., Saltzman, E., Roberts, S.B., Long-term effects of 2 energy-restricted diets differing in glycemic load on dietary adherence, body composition, and metabolism in CALERIE: a 1-y randomized controlled trial. Am. J. Clin. Nutr. 85 (2007), 1023–1030.
12. Ellison, P.T., Panter-Brick, C., Lipson, S.F., O'Rourke, M.T., The ecological context of human ovarian function. Hum. Reprod., 1993, 2248–2258.
13. Ellison, P.T., Age and developmental effects on adult ovarian function. Rosetta, L., Mascie-Taylor, N.C.G., (eds.) Variability in Human Fertility: A Biological Anthropological Approach, 1996, Cambridge University Press, New York, 69–90.
14. Ellison, P.T., Developmental influences on adult ovarian function. Am. J. Hum. Biol., 1996, 725–734.
15. Eveleth, P.B., Tanner, J.M., Worldwide Variation in Human Growth. 2nd ed., 1990, Cambridge University Press, New York.
16. Fairburn, C.G., Harrison, P.J., Eating disorders. Lancet 361 (2003), 407–416.
17. Fontana, L., Hu, F.B., Optimal body weight for health and longevity: bridging basic, clinical, and population research. Aging Cell 13 (2014), 391–400.
18. Fontana, L., Partridge, L., Promoting health and longevity through diet: from model organisms to humans. Cell 161 (2015), 106–118.
19. 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.
20. Fontana, L., Klein, S., Holloszy, J.O., Premachandra, B.N., Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones. J. Clin. Endocrinol. Metab. 91 (2006), 3232–3235.
21. Fontana, L., Villareal, D.T., Weiss, E.P., Racette, S.B., Steger-May, K., Klein, S., Holloszy, J.O., Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized: controlled trial. Am. J. Physiol. Endocrinol. Metab. 293 (2007), E197–202.
22. Fontana, L., Villareal, D.T., Weiss, E.P., Racette, S.B., Steger-May, K., Klein, S., Holloszy, J.O., Calorie restriction or exercise: effects on coronary heart disease risk factors. A randomized: controlled trial. Am. J. Physiol. Endocrinol. Metab. 293 (2007), E197–202.
23. Fontana, L., Weiss, E.P., Villareal, D.T., Klein, S., Holloszy, J.O., Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans. Aging Cell 7 (2008), 681–687.
24. 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 (2010), 97–108.
25. Fontana, L., Partridge, L., Longo, V.D., Extending healthy life span-from yeast to humans. Science 328:5976 (2010), 321–326.
26. 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., Holloszy, J.O., 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.
27. Fox, C.S., Massaro, J.M., Hoffmann, U., Pou, K.M., Maurovich-Horvat, P., Liu, C.Y., Vasan, R.S., Murabito, J.M., Meigs, J.B., Cupples, L.A., D'Agostino, R.B. Sr., O'Donnell, C.J., Abdominal visceral and subcutaneous adipose tissue compartments: association with metabolic risk factors in the Framingham Heart Study. Circulation 116 (2007), 39–48.
28. Frankenfield, D.C., Muth, E.R., Rowe, W.A., The Harris-Benedict studies of human basal metabolism: history and limitations. J. Am. Diet. Assoc. 98 (1998), 439–445.
29. Garby, L., Kurzer, M.S., Lammert, O., Nielsen, E., Effect of 12 weeks’ light-moderate underfeeding on 24-hour energy expenditure in normal male and female subjects. Eur. J. Clin. Nutr. 42 (1988), 295–300.
30. Harper, J.M., Leathers, C.W., Austad, S.N., Does caloric restriction extend life in wild mice?. Aging Cell 5 (2006), 441–449.
31. 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.
32. Heilbronn, L.K., de Jonge, L., Frisard, M.I., DeLany, J.P., Larson-Meyer, D.E., Rood, J., Nguyen, T., Martin, C.K., Volaufova, J., Most, M.M., Greenway, F.L., Smith, S.R., Deutsch, W.A., Williamson, D.A., Ravussin, E., Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA: J. Am. Med. Assoc. 295 (2006), 1539–1548.
33. Heyman, M.B., Young, V.R., Fuss, P., Tsay, R., Joseph, L., Roberts, S.B., Underfeeding and body weight regulation in normal-weight young men. Am. J. Physiol. 263 (1992), R250–257.
34. Heymsfield, S.B., Childers, D., Beetsch, J., Allison, D.B., Pietrobelli, A., Body size and human energy requirements: reduced mass-specific resting energy expenditure in tall adults. J. Appl. Physiol. 103 (2007), 1543–1550.
35. Hindhede, M., The effect of food restriction during war on mortality in Copenhagen. J. Am. Med. Assoc. 74 (1920), 381–382.
36. Hofer, T., Fontana, L., Anton, S.D., Weiss, E.P., Villareal, D., Malayappan, B., Leeuwenburgh, C., Long-term effects of caloric restriction or exercise on DNA and RNA oxidation levels in white blood cells and urine in humans. Rejuvenation Res. 11 (2008), 793–799.
37. Holloszy, J.O., Fontana, L., Caloric restriction in humans. Exp. Gerontol. 42 (2007), 709–712.
38. Hsu, A.L., Murphy, C.T., Kenyon, C., Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 300 (2003), 1142–1145.
39. Jain, I.H., Zazzeron, L., Goli, R., Alexa, K., Schatzman-Bone, S., Dhillon, H., Goldberger, O., Peng, J., Shalem, O., Sanjana, N.E., Zhang, F., Goessling, W., Zapol, W.M., Mootha, V.K., Hypoxia as a therapy for mitochondrial disease. Science 352 (2016), 54–61.
40. Japan Ministry of Health, L.a.W., 2005. Journal of Health and Welfare Statistics. Health and Welfare Statistics Association, Tokyo.
41. Johnson, M.L., Distelmaier, K., Lanza, I.R., Irving, B.A., Robinson, M.M., Konopka, A.R., Shulman, G.I., Nair, K.S., Mechanism by which caloric restriction improves insulin sensitivity in sedentary obese adults. Diabetes 65 (2016), 74–84.
42. Kagawa, Y., Impact of Westernization on the nutrition of Japanese: changes in physique, cancer, longevity and centenarians. Prev. Med. 7 (1978), 205–217.
43. Kalm, L.M., Semba, R.D., They starved so that others be better fed: remembering Ancel Keys and the Minnesota experiment. J. Nutr. 135 (2005), 1347–1352.
44. Kalu, D.N., Hardin, R.R., Cockerham, R., Yu, B.P., Norling, B.K., Egan, J.W., Lifelong food restriction prevents senile osteopenia and hyperparathyroidism in F344 rats. Mech. Ageing Dev. 26 (1984), 103–112.
45. Kenyon, C., Chang, J., Gensch, E., Rudner, A., Tabtiang, R., A C elegans mutant that lives twice as long as wild type. Nature 366 (1993), 461–464.
46. Keys, A.B., Brozek, J., Henschel, A., Mickelson, O., Taylor, A., The Biology of Human Starvation. 1950, University of Minnesota Press, Minneapolis.
47. Kitzman, D.W., Brubaker, P., Morgan, T., Haykowsky, M., Hundley, G., Kraus, W.E., Eggebeen, J., Nicklas, B.J., Effect of caloric restriction or aerobic exercise training on peak oxygen consumption and quality of life in obese older patients with heart failure with preserved ejection fraction: a randomized clinical trial. JAMA: J. Am. Med. Assoc. 315 (2016), 36–46.
48. Larson-Meyer, D.E., Heilbronn, L.K., Redman, L.M., Newcomer, B.R., Frisard, M.I., Anton, S., Smith, S.R., Alfonso, A., Ravussin, E., Effect of calorie restriction with or without exercise on insulin sensitivity, beta-cell function, fat cell size, and ectopic lipid in overweight subjects. Diabetes Care 29 (2006), 1337–1344.
49. Larson-Meyer, D.E., Redman, L., Heilbronn, L.K., Martin, C.K., Ravussin, E., Caloric restriction with or without exercise: the fitness versus fatness debate. Med. Sci. Sports Exerc. 42 (2010), 152–159.
50. Lecoultre, V., Ravussin, E., Redman, L.M., The fall in leptin concentration is a major determinant of the metabolic adaptation induced by caloric restriction independently of the changes in leptin circadian rhythms. J. Clin. Endocrinol. Metab. 96 (2011), E1512–1516.
51. Lecoultre, V., Peterson, C.M., Covington, J.D., Ebenezer, P.J., Frost, E.A., Schwarz, J.M., Ravussin, E., Ten nights of moderate hypoxia improves insulin sensitivity in obese humans. Diabetes Care 36 (2013), e197–198.
52. Lee, R.B., The !Kung San: Men, Women, and Work in a Foraging Society. 1979, University of Chicago Press, Chicago, IL.
53. Lefevre, M., Redman, L.M., Heilbronn, L.K., Smith, J.V., Martin, C.K., Rood, J.C., Greenway, F.L., Williamson, D.A., Smith, S.R., Ravussin, E., Caloric restriction alone and with exercise improves CVD risk in healthy non-obese individuals. Atherosclerosis 203 (2009), 206–213.
54. 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.
55. Lippl, F.J., Neubauer, S., Schipfer, S., Lichter, N., Tufman, A., Otto, B., Fischer, R., Hypobaric hypoxia causes body weight reduction in obese subjects. Obesity 18 (2010), 675–681.
56. S. Loft, E.J. Velthuis-te Wierik, H. van den Berg, H.E. Poulsen, 1995. Energy restriction and oxidative DNA damage in humans. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 4 515–519.
57. Longo, V.D., Fontana, L., Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol. Sci. 31 (2010), 89–98.
58. Martin, C.K., Anton, S.D., Han, H., York-Crowe, E., Redman, L.M., Ravussin, E., Williamson, D.A., Examination of cognitive function during six months of calorie restriction: results of a randomized controlled trial. Rejuvenation Res. 10 (2007), 179–190.
59. Martin, C.K., Heilbronn, L.K., de Jonge, L., DeLany, J.P., Volaufova, J., Anton, S.D., Redman, L.M., Smith, S.R., Ravussin, E., Effect of calorie restriction on resting metabolic rate and spontaneous physical activity. Obesity 15 (2007), 2964–2973.
60. Martin, C.K., Bhapkar, M., Pittas, A.G., Pieper, C.F., Das, S.K., Williamson, D.A., Scott, T., Redman, L.M., Stein, R., Gilhooly, C.H., Stewart, T., Robinson, L., Roberts, S.B., Effect of calorie restriction on mood, quality of life, sleep, and sexual function in healthy nonobese adults: the CALERIE 2 randomized clinical trial. JAMA Intern. Med., 2016.
61. Martorell, R., Interrelationships between diet, infectious disease, and nutritional status. Greene, L.S., Johnston, F.E., (eds.) Social and Biological Predictors of Nutritional Status, Physical Growth, and Neurological Development, 1980, Academic Press, New York, 81–106.
62. 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., Barnard, D., Ward, W.F., Qi, W., Ingram, D.K., de Cabo, R., Impact of caloric restriction on health and survival in rhesus monkeys from the NIA study. Nature 489 (2012), 318–321.
63. 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., Sabatini, D.M., de Cabo, R., Fontana, L., Calorie restriction in humans inhibits the PI3K/AKT pathway and induces a younger transcription profile. Aging Cell 12 (2013), 645–651.
64. Meyer, T.E., Kovacs, 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.
65. Muller, M.J., Enderle, J., Pourhassan, M., Braun, W., Eggeling, B., Lagerpusch, M., Gluer, C.C., Kehayias, J.J., Kiosz, D., Bosy-Westphal, A., Metabolic adaptation to caloric restriction and subsequent refeeding: the Minnesota Starvation Experiment revisited. Am. J. Clin. Nutr. 102 (2015), 807–819.
66. Paglia, D.E., Walford, R.L., Atypical hematological response to combined calorie restriction and chronic hypoxia in Biosphere 2 crew: a possible link to latent features of hibernation capacity. Habitation 10 (2005), 79–85.
67. Perry, R.J., Samuel, V.T., Petersen, K.F., Shulman, G.I., The role of hepatic lipids in hepatic insulin resistance and type 2 diabetes. Nature 510 (2014), 84–91.
68. Pittas, A.G., Roberts, S.B., Das, S.K., Gilhooly, C.H., Saltzman, E., Golden, J., Stark, P.C., Greenberg, A.S., The effects of the dietary glycemic load on type 2 diabetes risk factors during weight loss. Obesity 14 (2006), 2200–2209.
69. Racette, S.B., Weiss, E.P., Villareal, D.T., Arif, H., Steger-May, K., Schechtman, K.B., Fontana, L., Klein, S., Holloszy, J.O., One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 61 (2006), 943–950.
70. Racette, S.B., Weiss, E.P., Villareal, D.T., Arif, H., Steger-May, K., Schechtman, K.B., Fontana, L., Klein, S., Holloszy, J.O., One year of caloric restriction in humans: feasibility and effects on body composition and abdominal adipose tissue. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 61 (2006), 943–950.
71. Racette, S.B., Das, S.K., Bhapkar, M., Hadley, E.C., Roberts, S.B., Ravussin, E., Pieper, C., DeLany, J.P., Kraus, W.E., Rochon, J., Redman, L.M., Approaches for quantifying energy intake and%calorie restriction during calorie restriction interventions in humans: the multicenter CALERIE study. Am. J. Physiol. Endocrinol. Metab. 302 (2012), E441–448.
72. Ravussin, E., Redman, L.M., Rochon, J., Das, S.K., Fontana, L., Kraus, W.E., Romashkan, S., Williamson, D.A., Meydani, S.N., Villareal, D.T., Smith, S.R., Stein, R.I., Scott, T.M., Stewart, T.M., Saltzman, E., Klein, S., Bhapkar, M., Martin, C.K., Gilhooly, C.H., Holloszy, J.O., Hadley, E.C., Roberts, S.B., A 2-year randomized controlled trial of human caloric restriction: feasibility and effects on predictors of health span and longevity. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 70 (2015), 1097–1104.
73. Redman, L.M., Heilbronn, L.K., Martin, C.K., Alfonso, A., Smith, S.R., Ravussin, E., Effect of calorie restriction with or without exercise on body composition and fat distribution. J. Clin. Endocrinol. Metab. 92 (2007), 865–872.
74. Redman, L.M., Rood, J., Anton, S.D., Champagne, C., Smith, S.R., Ravussin, E., Calorie restriction and bone health in young, overweight individuals. Arch. Intern. Med. 168 (2008), 1859–1866.
75. Redman, L.M., Heilbronn, L.K., Martin, C.K., de Jonge, L., Williamson, D.A., Delany, J.P., Ravussin, E., Metabolic and behavioral compensations in response to caloric restriction: implications for the maintenance of weight loss. PLoS One, 4, 2009, e4377.
76. Redman, L.M., Veldhuis, J.D., Rood, J., Smith, S.R., Williamson, D., Ravussin, E., Pennington, C.T., The effect of caloric restriction interventions on growth hormone secretion in nonobese men and women. Aging Cell 9 (2010), 32–39.
77. L.M. Redman, S.R. Smith, V. Dixit, E. Ravussin, 2014. Evidence of metabolic adaptation after 2 years of 25% calorie restriction in non-obese humans The Obesity Week conference − Abstract T- 3032-OR.
78. Rickman, A.D., Williamson, D.A., Martin, C.K., Gilhooly, C.H., Stein, R.I., Bales, C.W., Roberts, S., Das, S.K., The CALERIE Study: design and methods of an innovative 25% caloric restriction intervention. Contemp. Clin. Trials 32 (2011), 874–881.
79. Riordan, M.M., Weiss, E.P., Meyer, T.E., Ehsani, A.A., Racette, S.B., Villareal, D.T., Fontana, L., Holloszy, J.O., Kovacs, S.J., The effects of caloric restriction- and exercise-induced weight loss on left ventricular diastolic function. Am. J. Physiol. Heart Circ. Physiol. 294 (2008), H1174–1182.
80. Roberts, S.B., Paul, A.A., Cole, T.J., Whitehead, R.G., Seasonal changes in activity, birth weight and lactational performance in rural Gambian women. Trans. R. Soc. Trop. Med. Hyg., 1982, 668–678.
81. Rochon, J., Bales, C.W., Ravussin, E., Redman, L.M., Holloszy, J.O., Racette, S.B., Roberts, S.B., Das, S.K., Romashkan, S., Galan, K.M., Hadley, E.C., Kraus, W.E., Design and conduct of the CALERIE study: comprehensive assessment of the long-term effects of reducing intake of energy. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 66 (2011), 97–108.
82. Romashkan, S.V., Das, S.K., Villareal, D.T., Ravussin, E., Redman, L.M., Rochon, J., Bhapkar, M., Kraus, W.E., Safety of two-year caloric restriction in non-obese healthy individuals. Oncotarget 7 (2016), 19124–19133.
83. Soare, A., Cangemi, R., Omodei, D., Holloszy, J.O., Fontana, L., Long-term calorie restriction, but not endurance exercise, lowers core body temperature in humans. Aging (Albany NY) 3:4 (2011), 374–379.
84. Sonntag, W.E., Lynch, C.D., Cefalu, W.T., Ingram, R.L., Bennett, S.A., Thornton, P.L., Khan, A.S., Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 54 (1999), B521–538.
85. Stein, P.K., Soare, A., Meyer, T.E., Cangemi, R., Holloszy, J.O., Fontana, L., Caloric restriction may reverse age-related autonomic decline in humans. Aging Cell 11 (2012), 644–650.
86. Strom, A., Jensen, R.A., Mortality from circulatory diseases in Norway 1940-1945. Lancet 1 (1951), 126–129.
87. Suzuki, M., Wilcox, B.J., Wilcox, C.D., Implications from and for food cultures for cardiovascular disease: longevity. Asia Pac. J. Clin. Nutr. 10 (2001), 165–171.
88. System of Social and Demographic Statistics, 2016. Health and Medical Care. Ministry of Internal Affairs and Communications.
89. Tam, C.S., Covington, J.D., Ravussin, E., Redman, L.M., Little evidence of systemic and adipose tissue inflammation in overweight individuals(dagger). Front. Genet., 3, 2012, 58.
90. Tatsumi, S., Ito, M., Asaba, Y., Tsutsumi, K., Ikeda, K., Life-long caloric restriction reveals biphasic and dimorphic effects on bone metabolism in rodents. Endocrinology 149 (2008), 634–641.
91. Tofler, G.H., Massaro, J., O'Donnell, C.J., Wilson, P.W., Vasan, R.S., Sutherland, P.A., Meigs, J.B., Levy, D., D'Agostino, R.B. Sr., Plasminogen activator inhibitor and the risk of cardiovascular disease: the Framingham Heart Study. Thromb. Res. 140 (2016), 30–35.
92. Ulijaszek, S.J., Nutritional status and susceptibility to infectious disease. Harrison, G.A., Waterlow, J.C., (eds.) Diet and Disease, 1990, Cambridge University Press, New York, 137–154.
93. Velthuis-te Wierik, E.J., van den Berg, H., Schaafsma, G., Hendriks, H.F., Brouwer, A., Energy restriction, a useful intervention to retard human ageing? Results of a feasibility study. Eur. J. Clin. Nutr. 48 (1994), 138–148.
94. Velthuis-te Wierik, E.J., Meijer, P., Kluft, C., van den Berg, H., Beneficial effect of a moderately energy-restricted diet on fibrinolytic factors in non-obese men. Metab. Clin. Exp. 44 (1995), 1548–1552.
95. Velthuis-te Wierik, E.J., van Leeuwen, R.E., Hendriks, H.F., Verhagen, H., Loft, S., Poulsen, H.E., Van den Berg, H., Short-term moderate energy restriction does not affect indicators of oxidative stress and genotoxicity in humans. J. Nutr. 125 (1995), 2631–2639.
96. Velthuis-te Wierik, E.J., Westerterp, K.R., van den Berg, H., Impact of a moderately energy-restricted diet on energy metabolism and body composition in non-obese men. Int. J. Obes. Relat. Metab. Disord. J. Int. Assoc. Stud. Obes. 19 (1995), 318–324.
97. Villareal, D.T., Fontana, L., Weiss, E.P., Racette, S.B., Steger-May, K., Schechtman, K.B., Klein, S., Holloszy, J.O., Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch. Intern. Med. 166 (2006), 2502–2510.
98. Villareal, D.T., Kotyk, J.J., Armamento-Villareal, R.C., Kenguva, V., Seaman, P., Shahar, A., Wald, M.J., Kleerekoper, M., Fontana, L., Reduced bone mineral density is not associated with significantly reduced bone quality in men and women practicing long-term calorie restriction with adequate nutrition. Aging Cell 10 (2011), 96–102.
99. Villareal, D.T., Fontana, L., Das, S.K., Redman, L., Smith, S.R., Saltzman, E., Bales, C., Rochon, J., Pieper, C., Huang, M., Lewis, M., Schwartz, A.V., Effect of two-year caloric restriction on bone metabolism and bone mineral density in non-obese younger adults: a randomized clinical trial. J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res. 31 (2016), 40–51.
100. Walford, R.L., Harris, S.B., Gunion, M.W., The calorically restricted low-fat nutrient-dense diet in Biosphere 2 significantly lowers blood glucose, total leukocyte count, cholesterol, and blood pressure in humans. Proc. Natl. Acad. Sci. U. S. A. 89 (1992), 11533–11537.
101. Walford, R.L., Mock, D., MacCallum, T., Laseter, J.L., Physiologic changes in humans subjected to severe, selective calorie restriction for two years in biosphere 2: health, aging, and toxicological perspectives. Toxicol. Sci. 52 (1999), 61–65.
102. 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. Ser. A Biol. Sci. Med. Sci. 57 (2002), B211–224.
103. Webb, P., Abrams, T., Loss of fat stores and reduction in sedentary energy expenditure from undereating. Hum. Nutr. Clin. Nutr. 37 (1983), 271–282.
104. Weindruch, R., Sohal, R.S., Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. N. Engl. J. Med. 337:14 (1997), 986–994.
105. Weiss, E.P., Racette, S.B., Villareal, D.T., Fontana, L., Steger-May, K., Schechtman, K.B., Klein, S., Holloszy, J.O., Improvements in glucose tolerance and insulin action induced by increasing energy expenditure or decreasing energy intake: a randomized controlled trial. Am. J. Clin. Nutr. 84 (2006), 1033–1042.
106. Weiss, E.P., Racette, S.B., Villareal, D.T., Fontana, L., Steger-May, K., Schechtman, K.B., Klein, S., Ehsani, A.A., Holloszy, J.O., Lower extremity muscle size and strength and aerobic capacity decrease with caloric restriction but not with exercise-induced weight loss. J. Appl. Physiol. 102 (2007), 634–640.
107. Weiss, E.P., Villareal, D.T., Racette, S.B., Steger-May, K., Premachandra, B.N., Klein, S., Fontana, L., Caloric restriction but not exercise-induced reductions in fat mass decrease plasma triiodothyronine concentrations: a randomized controlled trial. Rejuvenation Res. 11 (2008), 605–609.
108. Weyer, C., Snitker, S., Rising, R., Bogardus, C., Ravussin, E., Determinants of energy expenditure and fuel utilization in man: effects of body composition age, sex, ethnicity and glucose tolerance in 916 subjects. Int. J. Obes. Relat. Metab. Disord. J. Int. Assoc. Stud. Obes. 23 (1999), 715–722.
109. Weyer, C., Foley, J.E., Bogardus, C., Tataranni, P.A., Pratley, R.E., Enlarged subcutaneous abdominal adipocyte size, but not obesity itself, predicts type II diabetes independent of insulin resistance. Diabetologia 43 (2000), 1498–1506.
110. Willcox, D.C., Willcox, B.J., Todoriki, H., Curb, J.D., Suzuki, M., Caloric restriction and human longevity: what can we learn from the Okinawans?. Biogerontology 7 (2006), 173–177.
111. Willcox, B.J., Willcox, D.C., Todoriki, H., Fujiyoshi, A., Yano, K., He, Q., Curb, J.D., Suzuki, M., Caloric restriction, the traditional Okinawan diet, and healthy aging: the diet of the world's longest-lived people and its potential impact on morbidity and life span. Ann. N. Y. Acad. Sci. 1114 (2007), 434–455.
112. Willcox, B.J., Willcox, D.C., Todoriki, H., Yano, K., Curb, D., Suzuki, M., Caloric restriction, energy balance and healthy aging in Okinawans and Americans: biomarker differences in septuagenarians. Okinawan J. Am. Stud. 4 (2007), 62–74.
113. Williamson, D.A., Martin, C.K., Anton, S.D., York-Crowe, E., Han, H., Redman, L., Ravussin, E., Is caloric restriction associated with development of eating-disorder symptoms? Results from the CALERIE trial. Health Psychol. Off. J. Div. Health Psychol. Am. Psychol. Assoc. 27 (2008), S32–42.
114. Yang, L., Licastro, D., Cava, E., Veronese, N., Spelta, F., Rizza, W., Bertozzi, B., Villareal, D.T., Hotamisligil, G.S., Holloszy, J.O., Fontana, L., Long-term calorie restriction enhances cellular quality-control processes in human skeletal muscle. Cell Rep. 14 (2016), 422–428.
115. Yokoyama, K., Fukumoto, K., Murakami, T., Harada, S., Hosono, R., Wadhwa, R., Mitsui, Y., Ohkuma, S., Extended longevity of Caenorhabditis elegans by knocking in extra copies of hsp70F, a homolog of mot-2 (mortalin)/mthsp70/Grp75. FEBS Lett. 516 (2002), 53–57.