Beyond the rodent model: Calorie restriction in rhesus monkeys

Lane, Mark A.; Ingram, Donald K.; Roth, George S.

doi:10.1007/s11357-997-0004-2

Cited by 77 publications

(46 citation statements)

References 59 publications

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“…Female rhesus macaques, aged 7-27 years, showed no adverse effects of long-term 30% CR Lane et al 2001;Mattison et al 2003;Wu 2006). Moderate CR begun in prepubertal male rhesus macaques caused delayed sexual maturation and an associated slower increase in circulating testosterone (Lane et al 1997;Roth et al 2000). Concomitantly, skeletal growth was also limited in these animals (Roth et al 2000;Mattison et al 2003).…”

Section: Impact Of Moderate Calorie Restriction On Reproductionmentioning

confidence: 97%

“…Some of the beneficial health effects of CR include reduced adiposity, lower body temperature, lower blood pressure, reduction of glucose, fasting plasma insulin levels, and high density lipoproteins while increasing insulin sensitivity. CR affects neuroendocrine systems, reducing levels of growth hormone, thyroid-stimulating hormone and thyroid hormones, insulin-like growth factor 1, gonadotropins, and oxidative stress (Lane et al 1997;Gresl et al 2001;Heilbronn and Ravussin 2003;Koubova and Guarente 2003;Gredilla and Barja 2005). The degree and duration of CR influences the benefits of CR on rates of survival and aging (Merry 2002).…”

Section: Effects Of Calorie Restrictionmentioning

confidence: 99%

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Aging in male primates: reproductive decline, effects of calorie restriction and future research potential

Sitzmann

Urbanski

Ottinger

2008

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Although less dramatic than in females, male mammals experience decreasing reproductive function during aging. In primates, multiple facets of the hypothalamic-pituitary-gonadal axis show evidence of gradual age-related decline, including behavioral, neuroendocrine and endocrine alterations such as decreased testosterone levels, reduced circulating dehydroepiandrosterone sulfate (DHEAS) levels, increased numbers of sperm abnormalities, and a general decline in physiological responses. In this review we consider a range of age-related changes in males. These measures, including more subtle aging characteristics, are interesting additional indices for detecting the timing of age-related changes in behavioral, neuroendocrine, and endocrine responses. Evidence of potential effects of calorie restriction as an intervention in reproductive aging is also discussed. A discernable decline occurs in both metabolic and reproductive endocrine processes during male aging. This cascade of events includes neuroendocrine and behavioral changes; biomarkers such as circulating DHEAS also show clear age-related decline. The varied changes that occur during male aging are considered in the context of primate aging in general.

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Section: Impact Of Moderate Calorie Restriction On Reproductionmentioning

confidence: 97%

Section: Effects Of Calorie Restrictionmentioning

confidence: 99%

Aging in male primates: reproductive decline, effects of calorie restriction and future research potential

Sitzmann

Urbanski

Ottinger

2008

AGE

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“…It subsequently has been shown that caloric restriction (CR) can lengthen the life span of a wide variety of animals (2). Trials have even begun with higher primates; based on preliminary evidence, calorically restricted rhesus monkeys show similar signs of delayed aging to those seen in the calorically restricted rodents (3)(4)(5)(6)(7). CR has been best studied in rodents, and it is known that rodents undergoing CR display many physiological changes, including reduced body weight, temperature, blood glucose, and insulin levels (reviewed in refs.…”

mentioning

confidence: 99%

The genetics of caloric restriction in Caenorhabditis elegans

Lakowski

Hekimi

1998

Proc. Natl. Acad. Sci. U.S.A.

890

749

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Low caloric intake (caloric restriction) can lengthen the life span of a wide range of animals and possibly even of humans. To understand better how caloric restriction lengthens life span, we used genetic methods and criteria to investigate its mechanism of action in the nematode Caenorhabditis elegans. Mutations in many genes (eat genes) result in partial starvation of the worm by disrupting the function of the pharynx, the feeding organ. We found that most eat mutations significantly lengthen life span (by up to 50%). In C. elegans, mutations in a number of other genes that can extend life span have been found. Two genetically distinct mechanisms of life span extension are known: a mechanism involving genes that regulate dauer formation (age-1, daf-2, daf-16, and daf-28) and a mechanism involving genes that affect the rate of development and behavior (clk-1, clk-2, clk-3, and gro-1). We find that the long life of eat-2 mutants does not require the activity of DAF-16 and that eat-2; daf-2 double mutants live even longer than extremely long-lived daf-2 mutants. These findings demonstrate that food restriction lengthens life span by a mechanism distinct from that of dauer-formation mutants. In contrast, we find that food restriction does not further increase the life span of long-lived clk-1 mutants, suggesting that clk-1 and caloric restriction affect similar processes.It was shown more than 50 years ago that reducing the caloric intake (caloric restriction) of rodents can significantly lengthen their mean and maximal life span (1). It subsequently has been shown that caloric restriction (CR) can lengthen the life span of a wide variety of animals (2). Trials have even begun with higher primates; based on preliminary evidence, calorically restricted rhesus monkeys show similar signs of delayed aging to those seen in the calorically restricted rodents (3-7). CR has been best studied in rodents, and it is known that rodents undergoing CR display many physiological changes, including reduced body weight, temperature, blood glucose, and insulin levels (reviewed in refs. 8 and 9). However, it is unclear which of these changes are required for an extended life span (8, 9). Several studies indicate that reducing caloric intake reduces the amount of damage attributable to free radicals (reviewed in refs. 8 and 9). One simple hypothesis to explain how CR extends life span is that CR may reduce basal metabolic rates. Rodents and primates undergoing CR have lowered body temperatures (10-12), an indication of lower metabolic rates. However, studies on the effect of CR on the metabolic rates of various mammals have given equivocal results, with some studies showing no change in oxygen consumption per unit of lean body mass (13,14) and other studies showing a decrease of consumption under CR (15, 16). In spite of uncertainty about how CR affects life span, it remains the only experimental treatment that has been shown repeatedly to significantly prolong the life of vertebrates (8,9,17).On the other hand, it is in Cae...

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“…These include 1) prevention of late-onset (type II) diabetes (Hansen and Bodkin, 1993); 2) improvement in insulin sensitivity ; 3) reduction of triglycerides and increased HDL2 b , a high-density lipoprotein (HDL) subfraction associated with protection from cardiovascular disease (Verdery et al, 1997); 4) a slowing of the age-related decline in serum dehydroepiandrosterone sulfate (DHEAS) levels (Lane et al, 1997b); and 5) reduction in body temperature (Lane et al, 1996). Similar positive physiological effects of CR have been reported for rodents (Weindruch and Walford, 1988;French, 1992;Yu, 1994a,b;Weindruch, 1996).…”

Section: Discussionmentioning

confidence: 99%

Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta)

et al. 1999

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Caloric restriction (CR) is the most successful method of extending both median and maximal lifespans in rodents and other short-lived species. It is not yet clear whether this method of life extension will be successful in longer-lived species, possibly including humans; however, trials in rhesus monkeys are underway. We have examined the cellular proliferative potential of cells from CR and AL (ad libitum fed) monkey skin cells using two different bioassays: colony size analysis (CSA) of dermal fibroblasts isolated and cloned directly from the skin and beta-galactosidase staining at pH 6.0 (BG-6.0) of epidermal cells in frozen sections of skin. Decreases in both proliferative markers occurred with age, but no differences were observed between CR and AL animals. Skin biopsies were obtained from AL and CR rhesus monkeys from two different aging colonies, one at the National Institute on Aging (NIA) and one at the University of Maryland-Baltimore (UMB). These biopsies were used as a source of tissue sections and cells for two biomarkers of aging assays. The CR monkeys had been maintained for 9-12 years on approximately 70% of the caloric intake of control AL animals. In the CSA studies, the fraction of small clones increased significantly and the fraction of large clones decreased significantly with increasing age in AL monkeys. The frequency of epidermal BG-6.0 staining cells increased with age in older (>22 years) AL monkeys, but most predominately in those of the UMB colony, which were somewhat heavier than the NIH AL controls. Old monkeys on CR tended to have fewer BG-6.0-positive cells relative to old AL-derived epidermis, but this effect was not significant. These results indicate that cellular proliferative potential declined with age in Macaca mulatta, but was not significantly altered by CR under these conditions. Although these experiments are consistent with an absence of effect of CR on monkey skin cell proliferative potential, we have found in previous experiments with mice that a longer duration of CR (as a fraction of total lifespan) was needed to demonstrate CR-related improvement in clone size in mice. Further studies on the now mid-aged monkeys will be needed as their age exceeds 20 years to conclusively rule out an effect of CR on proliferative potential of skin cells from these primates.

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Beyond the rodent model: Calorie restriction in rhesus monkeys

Cited by 77 publications

References 59 publications

Aging in male primates: reproductive decline, effects of calorie restriction and future research potential

Aging in male primates: reproductive decline, effects of calorie restriction and future research potential

The genetics of caloric restriction in Caenorhabditis elegans

Cellular proliferation potential during aging and caloric restriction in rhesus monkeys (Macaca mulatta)

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