Calorie Restriction in Nonhuman Primates: Implications for Age-Related Disease Risk

Summary: Calorie restriction (CR) probably reduces diabetes and heart disease markers in rhesus monkeys. It also probably maintains DHEAS levels.

Interestingness: 3

Paper by Mark A Lane, Angela Black, Donald K Ingram and George S Roth in the Journal of Anti-Aging Medicine, Volume 1, Issue 4, Winter 1998.

(((I had already read a follow up paper published in 2010, so I knew the movie continued to go relatively well, but not fantastically so. That detracted from the excitement. This paper focuses on the effects of CR on diabetes and cardiovascular disease, and by measuring biomarkers in the latter case. Mortality would have been more interesting, but most likely the numbers would have been too low at such an early stage of the study. In any case, since CR seems to be the only "easy" intervention to make a difference for now, it's still a relatively interesting read.)))

Calorie restriction (CR) (((lowering food calorie intake by about 30% while maintaining good nutrition))) extends lifespan in lots of short-lived species, including rotifers (((little water animals, about half a milimetre long))), water fleas (((same))), fish, spiders, hamsters, mice and rats. Doing the relevant controlled experiment in humans would be tricky and take a long time. Doing it on rhesus monkeys is a close approximation and until animal-liberationists bomb them, less problematic.

Four experiments are reviewed. Two proper long-term randomised control studies on groups of 200 and 80 monkeys, the first one (NIA) in its 12th year, starting on sets of 1-2 year olds, 3-5 year olds and of > 17 year old monkeys, and the second one (UW) on 8-14 year old monkeys (((lifespan of rhesus monkeys is around 40 years))). One of the others (BGWF) is a short term (4 years) study on the cardiovascular effects of CR on 32 8-year old crab-eating macaques, the study being in its second year. The final study (UMB) is on 8 weight-stabilised rhesus monkeys which by coincidence happened to have a food regime similar to CR monkeys.

From the NIA study, the following effects are seen on the monkeys:
Decreases in:

• Body weight


• Fat and lean mass


• Trunk to leg fat ratio


• Fasting glucose/insulin


• Metabolic rate (short term)


• Body temperature


• Triglycerides


• IGF-1/growth hormone


• IL-6


• Rate of decline of DHEAS


• Lymphocyte number

Increases in:

• Insulin sensitivity


• HDL_2B


• Time to sexual maturation


• Time to skeletal maturation (((table says opposite on these last two, but text is clearer)))

No changes in:

• Metabolic rate (long term)


• Locomotion


• Testosterone


• Estradiol, LH, FSH, Progesterone


• Wound closure rate


• Clonal proliferation


• Beta-galactidase senescent cells


• Lymphocyte calcium response

All of these agree with rodent CR studies, in the cases where the rodent data is available, except for the lymphocyte calcium response.

(((That could really do as a summary, but the paper had another eight pages to go)))

With regards to diabetes and glucose regulation, there is another handy table summarising all the studies:

Both big studies agree in all of the following results:

• Decrease in fasting glucose


• Decrease in fasting insulin


• Decrease in insulin response


• Increase in insulin sensitivity


• No increase in glucose tolerance

The small coincidental study disagrees with regards to fasting glucose and glucose tolerance, and the short term study with respect to fasting insulin.

The effect of CR on cardiovascular disease doesn't appear to be as clearly beneficial. While triglyceride levels decreased the effect on LDL, HDL and total cholesterol was not statistically significant. By analysing HDL fractions, an increase in HDL_2B levels was measured. In the female subset of monkeys, lower total cholesterol and blood pressure was measured in CR monkeys compared to control monkeys. Lower arterial stiffness was also measured in male CR monkeys.

(((A graph at the end shows lower rate of decline of DHEAS (dehydroepiandrosterone-sulfate) in male CR monkeys, which would probably be the most interesting part of the paper. The framing of the graph seems a bit too purposeful though (why only show 3 years between 6 and 9 years of age?) )))

Abstract follows:

Calorie restriction (CR)—undernutrition without malnutrition—ranks among the most reproducible and widely used research paradigms in gerontologic research. This intervention is the only manipulation that has been shown consistently to extend the life span, delay onset and slow tumor progression, and retard physiologic aging in many systems. A large body of literature exists documenting these remarkable effects in such diverse short-lived species as rotifers, water fleas, fish, spiders, hamsters, and laboratory mice and rats. However, it is not known if CR has similar effects in longer-lived species more closely related to humans. Two major studies in rhesus monkeys, one at the National Institute on Aging and the other at the University of Wisconsin, were begun several years ago to address this question. Two similar studies focusing mostly on disease end points such as obesity, diabetes, and cardiovascular disease are also underway at the University of Maryland and Bowman-Gray School of Medicine. These studies have clearly shown that most physiologic responses assessed in monkeys on CR parallel the extensive literature on rodents. This article focuses on data related to various risk factors for age-associated diseases, in particular diabetes and cardiovascular disease. Although it will be several more years before definitive results regarding life span are available, emerging data from the monkey studies strongly suggest that CR alters several disease risk factors and may affect postmaturational aging in some systems. Therefore, it is likely that this nutritional intervention will result in at least moderate increases in the primate life span related to amelioration of certain age-related diseases and their complications.