New findings suggest how caloric restriction may prolong healthy life
Researchers at the National Institute on Aging's (NIA) Gerontology Research Center (GRC) have shown for the first time that reducing calorie intake by 30 percent lowers body temperature in monkeys. This lowered body temperature is a result of a lowered metabolic rate due to limited food intake. The next step for NIA researchers is to look for a relationship between reduced metabolic rate and changes in longevity. The temperature finding in monkeys is similar to findings in rats and mice who lived longer when they were placed on calorie restricted diets. The results in monkeys appear in the April 30,1996 Proceedings of the National Academy of Sciences (PNAS).
The NIA study of nearly 200 rhesus and squirrel monkeys began in 1987. Scientists based their investigations on knowledge gleaned from 60 years of research in rodents and other small animal species that showed reduced calorie intake can extend lifespan, maintain vitality, and delay or reduce the incidence of age-associated disease. Until recently, no one had studied caloric restriction's effects in primates or the mechanisms by which these effects might occur.
According to NIA scientist Dr. George Roth, "this work in monkeys raises the possibility that the beneficial effects of caloric restriction may occur in higher primates and might even someday include humans."
This study demonstrates that reducing calorie intake by 30 percent (and still providing a nutritionally balanced diet) in young monkeys leads to a reduction in their metabolic rate and their body temperature. Older monkeys (and most other mammals) use a large part of their food intake to maintain a relatively high body temperature. In people, reduced body temperature due to caloric restriction has been seen only in starvation studies where caloric restriction is greater than 30 percent.
Leading the caloric restriction research at the GRC are Drs. Roth, Donald K. Ingram, and Mark A. Lane. They are joined in this and other studies by scientists at the Department of Agriculture, Case Western Reserve University, the University of Texas at San Antonio, and several other institutions.
According to Dr. Lane, "the finding that body temperature is reduced in monkeys when they are adapting to a moderate 30 percent caloric restriction is interesting. We have seen reduced body temperature both during the initial adaptation to reduced feeding and while the monkeys were on caloric restriction for several years."
The authors speculate that caloric restriction reduces body temperature, which in turn affects various factors at a molecular level. For instance, reduced temperature might affect longevity as a result of its impact on various cellular processes such as DNA damage and repair and the development of certain tumors.
In an earlier PNAS article (Vol. 93: January 26,1996), the authors discussed how the end product of a complex biochemical chain reaction could be a possible "biomarker" of aging (a signal or flag that provides a way to measure the aging process). The biomarker in question in this study is a chemical compound called pentosidine. Although seen in many tissues in the body, pentosidine is most easily detected in a substance in the skin called collagen.
Other studies have shown that increased pentosidine levels with age correlate strongly with the severity of complications in diabetes and end-stage renal disease.
In caloric restriction studies, those animals on restricted diets had a slower accumulation of pentosidine, supposedly leading to greater collagen elasticity, fewer disease complications, and possibly a healthier and longer life.
For the pentosidine study, colleagues at Case Western Reserve University, under the direction of Dr. Vincent Monnier, examined five different animal species, from small, short-lived animals to larger, longer-lived NIA monkeys. All of the species showed significantly higher levels of pentosidine with increasing age. Additionally, the rate of pentosidine increase was greater for rats on normal diets, than for those that were on calorically restricted diets. Preliminary data suggest that a similar phenomenon may occur in monkeys. This is a strong indication that a process which leads to pentosidine formation may be associated with one of the determinates of longevity.
One of the principal benefits of pentosidine studies for investigators may be its use as a biomarker of aging. According to Drs. Roth and Ingram, one aspect of a good biomarker of aging is that the rate of change of that biomarker "flag" must be accelerated in species that have short life spans when compared to those with longer life spans. In addition, life-prolonging interventions such as caloric restriction must also be shown to retard this aging marker. Indeed, in comparing life spans among the five animal species studied, the above qualifications held true when pentosidine was the biomarker being examined.
Dr. Roth believes that "pentosidine and body temperature may be only two of many aspects of aging that exhibit lower levels in calorically restricted animals." Initial results from other studies in primates by Dr. Roth and colleagues are due by the end of the decade. These results could provide additional biomarkers for future studies of interventions that would be aimed at slowing the aging process or reducing disability.
The National Institute on Aging, part of the National Institutes of Health, leads the Federal effort supporting basic, clinical, epidemiological, and behavioral research on aging and the special needs of older people.