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Caloric restriction for six months produces interesting biochemical and metabolic changes associated with anti-aging
(September 2006)

The most predictable and effective way of modifying the aging process and increasing longevity in a variety of non-human species is caloric restriction.  A 30 to 40 percent reduction in caloric intake (without malnutrition) can increase life spans by 30 percent to more than 300 percent.  In rat models, lesser caloric restriction plus increased physical exertion can produce similar life extension.  As the exciting studies moved from yeast cells to earthworms and fruit flies and then to mice and rats, the obvious question was whether the results of animal experiments would be found in primates, including humans.  A 25-year study of calorically-restricted Rhesus monkeys is now about half way through its planned course.  It shows changes in body temperature (lowered), insulin levels (lowered), and the hormone dehydroepiandrosterone (higher) that are similar to findings in rodents and suggest that the life-extending effects of caloric restriction will apply to primates.  A small number of preliminary studies in long-lived or calorically-restricted humans have reported biochemical and physiologic findings similar to some of those found in monkeys and rodents.  Add to these studies in humans an interesting study of six months of caloric restriction in 48 overweight men and women, average age 38 years, average weight 180 pounds published in the April 5, 2006 issue of the Journal of the American Medical Association.  Participants were divided into four groups of twelve each: (a) controls; (b) 25 percent reduced calorie diet; (c) 12.5 percent reduction in calories plus an exercise program; (d) a very low calorie diet (890 calories a day) designed to achieve a 15 percent weight loss.

All three intervention groups lost weight, ranging from, on average, 22 to 31 pounds.  Blood insulin levels fell significantly in all three intervention groups.  Body temperature fell in both calorie restriction groups, but not in the very low calorie diet group.  Energy expenditure decreased in all three intervention groups.  Thyroid hormone blood levels and DNA cellular damage were also significantly decreased in the three intervention groups, but there was no change in dehydroepiandrosterone (DHEA) levels.

The authors conclude “our findings suggest that two biomarkers of longevity (fasting insulin level and body temperature) are decreased by prolonged calorie restriction in humans and support the theory that the metabolic rate is reduced”.

Commentary: This is an important study.  It shows that some of the markers of increased longevity found in rodents and monkeys are also found in calorically-restricted humans.  One of the expected markers, higher DHEA levels, was not found.  Additionally, although oxidative stress is thought to be a critical variable in aging, there was no specific evidence found in this study of reduced oxidative stress, though the reduced DNA damage suggests it might have occurred.

This study needs to be replicated and expanded, but the bottom line is that the animal studies do seem relevant to humans and we are getting ever closer to an understanding of the mechanisms of aging and anti-aging that will permit use of pharmacologic agents developed from that understanding to attempt to extend life spans.  That is exciting, but it also brings up daunting societal challenges (see Archives under Aging, “Extraordinary longevity:   Individual and societal issues”.)

Very interesting, indeed, but let us be very clear.  There is, at present, no prescription drug, alternative medicine, herb, or any other substance that can modify the aging process and let us live longer.  Currently, all we can do is prevent or treat effectively specific diseases that occur frequently as we age (heart disease, stroke, cancer, etc).

Heilbronin, L.K., et al.  Effect of six-month caloric restriction on biomarkers of longevity, metabolic adaptation and oxidative stress in overweight individuals.  Journal of the American Medical Association.   Vol 295 (April 5) Pgs 1539-1548.  2006.