Two New Studies Suggest That Caloric Restriction In Monkeys May Extend Their Life And Health

One new study from the National Institute on Aging (NIA) and Dr. Roy Verdery atthe Arizona Center on Aging shows that a 30 percent reduction in calories in amonkey's diet leads to elevation in good cholesterol (HDL2B) levels with asubsequent reduction in risk for cardiovascular disease. A second recent studyfrom the NIA has shown that caloric restriction slows the age-related decreasein amounts of a naturally occurring steroid hormone, DHEA. Using natural DHEAlevels as a biomarker of aging may assist scientists in their search for a wayto slow down the aging process.

Previous research in shorter-lived species such as fruit flies and rats hasdemonstrated that a 30 percent caloric restriction can lead to 30 percent longerlife 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 percentreduction in caloric intake in rhesus monkeys leads to up to a 25 pointelevation in HDL2B levels as well as a 20 point decrease in triglyceride levels(as measured in milligrams per deciliter). Increases in HDL2B and decreases intriglycerides of this magnitude in humans would be a great health benefit tomany, especially for those at risk for stroke or heart attack.

Principal investigator, George Roth, Ph.D., Acting Chief of NIA's Laboratory ofCellular and Molecular Biology, says, "In addition to enhanced HDL2B and lowertriglyceride levels, we also see a small drop in blood pressure. These HDL2Bresults, combined with previous findings from our lab showing better glucosetolerance and insulin sensitivity (which should predict lower incidence ofdiabetes), lower body temperature, and other such biomarkers suggesting thatcaloric restriction may exert beneficial effects in primates similar to those previously observed in rodents. These results may someday serve as amodel for human studies."

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

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

The second study from Drs. Roth, Lane, and Donald Ingram at NIA and Dr. SheldonBall at the University of San Francisco-Fresno, appeared in the July 1997 issueof 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 thanthose observed in control monkeys.

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

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

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

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