Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study

Dietary restriction (DR) retards aging and extends the maximum lifespan of laboratory mice and rats. To determine whether DR has similar actions in a primate species, we initiated a study in 1989 to investigate the effects of a 30% DR in 30 adult male rhesus monkeys. In 1994, an additional 30 females and 16 males were added to the study. Although the animals are still middle-aged, a few differences have developed between the control and DR animals suggesting that DR may induce physiologic changes in the rhesus monkey similar to those observed in rodents. Fasting basal insulin and glucose concentrations are lower in DR compared to control animals while insulin sensitivity is higher in the restricted animals. DR has also altered circulating LDL in a manner that may inhibit atherogenesis. These results suggest that DR may be slowing some age-related physiologic changes. In addition to measures of glucose and lipid metabolism, the animals are evaluated annually for body composition, energy expenditure, physical activity, hematologic indices, and blood or urinary hormone concentrations. In the next few years, the first animals will reach the average lifespan ( approximately 26 years) of captive rhesus monkeys and it will become possible to determine if DR retards the aging process and extends the lifespan in a primate species.

[1]  R. Weindruch,et al.  Energy expenditure of adult male rhesus monkeys during the first 30 mo of dietary restriction. , 1997, The American journal of physiology.

[2]  B. Yu.  Modulation of aging processes by dietary restriction , 1994 .

[3]  Y. Higami,et al.  A role for leptin in the antiaging action of dietary restriction: A hypothesis , 1999, Aging.

[4]  R. Reiter,et al.  The pineal gland and melatonin in relation to aging: A summary of the theories and of the data , 1995, Experimental Gerontology.

[5]  P. Kaufman,et al.  Dietary restriction of adult male rhesus monkeys: design, methodology, and preliminary findings from the first year of study. , 1993, Journal of gerontology.

[6]  D. Harman,et al.  The aging process. , 1981, Proceedings of the National Academy of Sciences of the United States of America.

[7]  D. Allison,et al.  Caloric restriction of rhesus monkeys lowers oxidative damage in skeletal muscle , 2000, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[8]  J. Wishart,et al.  Effect of age on bone density and bone turnover in men , 1995, Clinical endocrinology.

[9]  D. Ingram,et al.  Diet restriction in rhesus monkeys lowers fasting and glucose-stimulated glucoregulatory end points. , 1995, The American journal of physiology.

[10]  B. Hansen,et al.  Primary Prevention of Diabetes Mellitus by Prevention of Obesity in Monkeys , 1993, Diabetes.

[11]  Caloric restriction. , 1998, Aging.

[12]  Edward L. Schneider,et al.  Handbook of the Biology of Aging , 1990 .

[13]  M. Hammerman,et al.  Insulin-like growth factors and aging. , 1987, Endocrinology and metabolism clinics of North America.

[14]  R. Colman,et al.  The effect of dietary restriction on body composition in adult male and female rhesus macaques , 1998, Aging.

[15]  D. Johnson,et al.  Metabolic rate, organ mass, and mitochondrial proton leak variations in lean and obese rats. , 1996, Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology.

[16]  M. Nicolson,et al.  Leptin Gene Expression Increases With Age Independent of Increasing Adiposity in Rats , 1997, Diabetes.

[17]  J. Florini,et al.  Effect of rat age on serum levels of growth hormone and somatomedins , 1981, Mechanisms of Ageing and Development.

[18]  Sing-yung Wu.  Thyroid hormone metabolism : regulation and clinical implications , 1991 .

[19]  L. Fishbein.  Biological Effects of Dietary Restriction , 2012, ILSI Monographs.

[20]  R. Bergman,et al.  Dietary restriction increases insulin sensitivity and lowers blood glucose in rhesus monkeys. , 1994, The American journal of physiology.

[21]  M. Vitiello,et al.  Sleep disorders and aging: understanding the causes. , 1997, The journals of gerontology. Series A, Biological sciences and medical sciences.

[22]  B. McEwen,et al.  The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. , 1986, Endocrine reviews.

[23]  R. Weindruch,et al.  Adult-onset energy restriction of rhesus monkeys attenuates oxidative stress-induced cytokine expression by peripheral blood mononuclear cells. , 1997, The Journal of nutrition.

[24]  B. V. VON Schoultz,et al.  Dehydroepiandrosterone sulphate and dehydroepiandrosterone in serum: differences related to age and sex. , 1988, Maturitas.

[25]  R. Bergman.  Toward Physiological Understanding of Glucose Tolerance: Minimal-Model Approach , 1989, Diabetes.

[26]  R. Colman,et al.  Body fat distribution with long-term dietary restriction in adult male rhesus macaques. , 1999, The journals of gerontology. Series A, Biological sciences and medical sciences.

[27]  J. T. Herlihy,et al.  Long-term food restriction depresses serum thyroid hormone concentrations in the rat , 1990, Mechanisms of Ageing and Development.

[28]  R. Goy,et al.  Ovarian hormones and food intake in female guinea pigs and rhesus monkeys , 1975, Hormones and Behavior.

[29]  B. Kristal,et al.  An emerging hypothesis: synergistic induction of aging by free radicals and Maillard reactions. , 1992, Journal of gerontology.

[30]  R. Weindruch,et al.  Caloric restriction in rhesus monkeys reduces low density lipoprotein interaction with arterial proteoglycans. , 1998, The journals of gerontology. Series A, Biological sciences and medical sciences.

[31]  E. Roecker,et al.  Serum dehydroepiandrosterone sulfate concentrations across the life span of laboratory‐housed rhesus monkeys , 2000, Journal of medical primatology.

[32]  R. Watson,et al.  Dehydroepiandrosterone and Diseases of Aging , 1996, Drugs & aging.

[33]  R. L. Moore,et al.  Impaired leptin responsiveness in aged rats. , 2000, Diabetes.

[34]  H. Feit.  Thyroid function in the elderly. , 1988, Clinics in geriatric medicine.

[35]  Z. Barrou,et al.  Dehydroepiandrosterone (DHEA) and aging. , 1997, Archives of gerontology and geriatrics.

[36]  C. Breese,et al.  Influence of age and long-term dietary restriction on plasma insulin-like growth factor-1 (IGF-1), IGF-1 gene expression, and IGF-1 binding proteins. , 1991, Journal of gerontology.

[37]  R. Weindruch,et al.  Oxidative Stress, Caloric Restriction, and Aging , 1996, Science.

[38]  D. Ingram,et al.  Short-term calorie restriction improves disease-related markers in older male rhesus monkeys (Macaca mulatta) , 2000, Mechanisms of Ageing and Development.

[39]  D. Harman.  Aging: a theory based on free radical and radiation chemistry. , 1956, Journal of gerontology.

[40]  C. Sen,et al.  Handbook of oxidants and antioxidants in exercise , 2000 .

[41]  L. S. Felicio,et al.  Neuroendocrine involvement in aging: Evidence from studies of reproductive aging and caloric restriction , 1995, Neurobiology of Aging.

[42]  R. Weindruch,et al.  Part X • Chapter 29 – Oxidative stress and the pathogenesis of sarcopenia , 2000 .

[43]  Ultradian rhythms in waking behavior of rhesus monkeys , 1978, Physiology & Behavior.

[44]  R. Weindruch,et al.  Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. , 1982, Science.

[45]  R. Walford,et al.  The response to calorie restriction in mammals shows features also common to hibernation: a cross-adaptation hypothesis. , 1997, The journals of gerontology. Series A, Biological sciences and medical sciences.

[46]  F. Plum.  Handbook of Physiology. , 1960 .

[47]  S. Schapiro,et al.  Behavioral effects of enrichment on singly‐housed, yearling rhesus monkeys: An analysis including three enrichment conditions and a control group , 1995, American journal of primatology.

[48]  D. Ingram,et al.  Dehydroepiandrosterone sulfate: a biomarker of primate aging slowed by calorie restriction. , 1997, The Journal of clinical endocrinology and metabolism.

[49]  R. W. Kuhn,et al.  Assessment of the role of the glucocorticoid system in aging processes and in the action of food restriction. , 1991, Journal of gerontology.

[50]  Richard Weindruch,et al.  The Retardation of Aging and Disease by Dietary Restriction , 1988 .

[51]  N. Orentreich,et al.  Age changes and sex differences in serum dehydroepiandrosterone sulfate concentrations throughout adulthood. , 1984, The Journal of clinical endocrinology and metabolism.