Two recent animal studies offer a possible explanation for how caloric restriction might possibly enhance human health and help extend life as well. One new study from the National Institute on Aging (NIA) and Dr. Roy Verdery at the Arizona Center on Aging shows that a 30 percent reduction in calories in a monkey's diet leads to elevation in good cholesterol (HDL_2B) levels with a subsequent reduction in risk for cardiovascular disease. A second recent study from the NIA has shown that caloric restriction slows the age-related decrease in amounts of a naturally occurring steroid hormone, DHEA. Using natural DHEA levels as a biomarker of aging may assist scientists in their search for a way to slow down the aging process.

Previous research in shorter-lived species such as fruit flies and rats has demonstrated that a 30 percent caloric restriction can lead to 30 percent longer life in addition to enhanced markers of good health.

The first of the two studies (American Journal of Physiology, October, 1997, Vol. 36, No. 4) demonstrates that, over a ten year period, a 30 percent reduction in caloric intake in rhesus monkeys leads to up to a 25 point elevation in HDL_2B levels as well as a 20 point decrease in triglyceride levels (as measured in milligrams per deciliter). Increases in HDL_2B and decreases in triglycerides of this magnitude in humans would be a great health benefit to many, especially for those at risk for stroke or heart attack.

Principal investigator, George Roth, Ph.D., Acting Chief of NIA's Laboratory of Cellular and Molecular Biology, says, "In addition to enhanced HDL2B and lower triglyceride levels, we also see a small drop in blood pressure. These HDL_2B results, combined with previous findings from our lab showing better glucose tolerance and insulin sensitivity (which should predict lower incidence of diabetes), lower body temperature, and other such biomarkers suggesting that caloric restriction may exert beneficial effects in primates similar to those previously observed in rodents. These results may someday serve as a model for human studies."

One interesting aspect of this particular study is that neither the control monkeys nor the calorically restricted monkeys eat much fat or cholesterol as part of their diets. Thus the study demonstrates that even in non-obese monkeys, a reduction in calorie intake can benefit cholesterol, triglycerides and blood pressure. This research presents an important contrast to studies that usually look at obesity and how weight loss from that level can benefit health. It is demonstrated here for the first time that caloric restriction can lead to changes in HDLs and other lipid profiles that may be associated with health benefits for both those animals that are lean as well as those that are heavier.

Recent research under the direction of Mark Lane, Ph.D., Senior Staff Fellow at the NIH's Animal Center, has turned up an interesting added benefit to caloric restriction. In addition to boosting good cholesterol and reducing triglycerides, monkeys on caloric restricted diets experience a favorable redistribution of fat away from their central regions thus reinforcing the current finding about reduction in cardiovascular risk with caloric restriction.

The second study from Drs. Roth, Lane, and Donald Ingram at NIA and Dr. Sheldon Ball at the University of San Francisco-Fresno, appeared in the July 1997 issue of the Journal of Clinical Endocrinology and Metabolism (Vol. 82, No. 7, pp. 2093-2096). In this study, monkeys whose calorie intake was restricted by 30 percent showed a slower decline in DHEAS (dehydroepi-androsterone sulfate) and DHEA (the unsulfated form) levels than those observed in control monkeys.

Dr. Lane, principal investigator of this study, says, "DHEA levels are of great interest to us, not because we believe that DHEA is the fountain of youth, but rather because it gives us a very good marker to measure the rates of aging in control versus calorically restricted monkeys. It is important to distinguish between levels of DHEA that occur naturally in the body and decline with age and levels that are seen in people who pop DHEA pills to pharmacologically raise their natural levels in hope of extending their lives. These artificially higher levels may or may not give them any benefit. Controlled clinical trials are needed before this question can be answered." Dr. Ingram adds, "It is important to develop markers such as DHEAS which can be used to determine the effects of various interventions, such as diet and exercise, on aging."

According to Dr. Roth, "this study shows that monkeys eating a calorically restricted diet which contains little fat maintain higher DHEA levels in their bodies. In this setting, DHEA is a marker of aging. We do not yet know if DHEA plays a role in slowing the aging process."

Until NIA initiated studies in rhesus monkeys in 1987, the phenomena of longer life and better health and vigor through caloric restriction had never been investigated in longer-lived primate species. These studies will continue for many more years with the goal of eventually giving a more precise understanding of the mechanisms of how caloric restriction extends life.

The National Institute on Aging, one of the 18 Institutes which make up the National Institutes of Health, leads the Federal effort supporting basic, clinical, epidemiological and social research on aging and the special needs of older people. A brochure, "Pills, Patches and Shots: Can Hormones Prevent Aging?" is available from the NIA by calling 1-800-222-2225 or by visiting the NIA's website at http://www.nih.gov/nia

Note: Video B-roll/VNR on betacam and 8x10 color stills of the monkeys in this study are available for broadcast or print use by calling (301)496-1752.