Caloric restriction (CR), which has been investigated by gerontologists for more than 60 yr, provides the only intervention tested to date in mammals (typically mice and rats) that repeatedly and strongly increases maximum life span while retarding the appearance of age-associated pathologic and biologic changes. Although the large majority of rodent studies have initiated CR early in life (1-3 mo of age), CR started in midadulthood (at 12 mo) also extends maximum life span in mice. Two main questions now face gerontologists investigating CR. By what mechanisms does CR retard aging and disease processes in rodents? There is evidence to suggest that age-associated increases in oxidative damage may represent a primary aging process that is attenuated by CR. Will CR exert similar actions in primates? Studies in rhesus monkeys subjected to CR and limited human epidemiological data support the notion of human translatability. However, no matter what the answers are to these questions, the prolongation of the health span and life span of rodents by CR has major implications for many disciplines, including toxicologic pathology, and raises important questions about the desirability of ad libitum feeding.
Fishbein L (ed) (1991). Biological Effects of Dietary Restriction. Springer-Verlag , New York.
2.
Hansen BC, Ortmeyer HK, and Bodkin NL (1995). Prevention of obesity in middle-aged monkeys-Food intake during body weight clamp. Obesity Res. 3(suppl. 2): S199-S204.
3.
Hart RW, Neuman DA , and Robinson RT (eds) ( 1995). Dietary Restriction: Implications for the Design and Interpretation of Toxicity and Carcinogenicity Studies. ILSI Press, Washington, D.C.
4.
Ingram DK, Cutler RG, Weindruch R., Renquist DM, Knapka JJ, April M., Belcher CT, Clark MA, Hatcherson CD, Marriott BM, and Roth GS (1990). Dietary restriction and aging: The initiation of a primate study. J. Gerontol. Biol. Sci. 45: B148-B163.
5.
Kagawa Y. (1978). Impact of Westernization on the nutrition of Japanese: Changes in physique, cancer, longevity, and centenarians. Prev. Med. 7: 205-217.
6.
Kemnitz JW, Roecker EB, Weindruch R., Elson DF, Baum ST, and Bergman RN (1994). Dietary restriction increases insulin sensitivity and lowers blood glucose in rhesus monkeys. Am. J. Physiol. Endocrinol. Metab. 266: E540-547.
7.
Kemnitz JW, Weindruch R., Roecker EB, Crawford K., Kaufman PL, and Ershler WB (1993). Dietary restriction of adult male rhesus monkeys: Design, methodology, and preliminary findings from the first year of study . J. Gerontol. Biol. Sci. 48: B17-B26.
8.
Lane MA, Baer DJ, Rumpler WV, Weindruch R., Ingram DK, Tilmont EM, Cutler RG, and Roth GS (1996). Calorie restriction lowers body temperature in rhesus monkeys, consistent with a postulated anti-aging mechanism in rodents . Proc. Natl. Acad. Sci. USA93: 4159-4164.
9.
Masoro EJ (1988). Food restriction in rodents: An evaluation of its role in the study of aging. J. Gerontol. Biol. Sci. 43: B59-B64.
10.
Sanderson J. , Binkley N., Roecker EB, Pugh TD, Aspnes L., and Weindruch R. (1996). Influence of fat intake and caloric restriction on bone in aging male rats . J. Gerontol. Biol. Sci. (in press).
11.
Snyder DL (ed) (1989). Dietary Restriction and Aging. Alan R. Liss, New York.
12.
Sohal RS and Weindruch R. (1996). Oxidative stress, caloric restriction, and aging . Science273: 59-63.
13.
Sweet M., Ntambi JA, Gaumnitz EA, Pugh TD, Weindruch R., and Singaram C. (1996). Neuropeptide Y- and peptide YY-containing colonic cells increase with aging in male rats. Neuropeptides30: 385-390.
14.
Velthuis-te Wierik EJ, Meijer P., Kluft C., and Van den Berg H. (1995). Beneficial effect of a moderately energy-restricted diet on fibrinolytic factors in non-obese men. Metabolism44: 1548-1552.
15.
Velthuis-te Wierik EJ, Van den Berg H., Schaafsma G., Hendriks HF, and Brouwer A. (1994). Energy restriction, a useful intervention to retard human ageing? Results of a feasibility study. Eur. J. Clin. Nutr. 48: 138-148.
16.
Velthuis-te Wierik EJ, Westerterp KR, and Van den Berg H. (1995). Impact of a moderately energy-restricted diet on energy metabolism and body composition in non-obese men. Intl. J. Obesity19: 318-324.
17.
Volk MJ, Pugh TD, Kim MJ, Frith CH, Daynes RA, Ershler WB, and Weindruch R. (1994). Dietary restriction from middle age attenuates age-associated lymphoma development and interleukin 6 dysregulation in C57BL/6 mice. Cancer Res. 54: 3054-3061.
18.
Walford RL, Harris SB, and Gunion MW (1992). 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. USA89: 11533-11537.
19.
Weindruch R. (1995). Interspecies variations in physiologic and antipathologic outcomes of dietary restriction. In: Dietary Restriction: Implications for the Design and Interpretation of Toxicity and Carcinogenicity Studies , RW Hart, DA Neumann, and RT Robertson (eds). ILSI Press, Washington, D.C., pp. 351-364.
20.
Weindruch R. (1996). Caloric restriction and aging. Sci. Am. 274(1): 46-52.
21.
Weindruch R. , Albanes D., and Kritchevsky D. (1991). The role of calories in carcinogenesis. Hematol. Oncol. Clin. N. Amer. 5: 79-89.
22.
Weindruch RH , Cheung MK, Verity MA, and Walford RL (1980). Modification of mitochondrial respiration by aging and dietary restriction . Mech. Ageing Dev. 12: 375-392.
23.
Weindruch R. and Walford RL (1982). Dietary restriction in mice beginning at one year of age: Effects on life-span and spontaneous cancer incidence. Science215: 1415-1418.
24.
Weindruch R. and Walford RL (1988). The Retardation of Aging and Disease by Dietary Restriction. Charles C Thomas, Springfield, Illinois.
25.
Weindruch R. , Walford RL, Fligiel S., and Guthrie D. (1986). The retardation of aging by dietary restriction in mice: Longevity, cancer, immunity and lifetime energy intake. J. Nutr. 116: 641-654.
26.
Yu BP (ed) (1994). Modulation of Aging Processes by Dietary Restriction. CRC Press, Boca Raton, Florida.
