Dietary energy restriction (ER) improves health and increase maximum life span in rats, mice, and other animals. A decrease in cellular oxygen consumption (OC) and a reduction in oxygen free radical production have both been proposed to play an important role in the retardation of aging by ER. These hypotheses may be combined to suggest that a reduction in OC may increase life span by decreasing the number of oxygen molecules interacting with the mitochondria and thus lowering free radical production. To test this theory, it is crucial that the effects of ER on whole animal, organ, and cellular OC are accurately determined. The hypothesis that ER causes a sustained and uniform decrease in cellular OC, however, can not be properly tested by whole animal studies. The internal organs are responsible for greater than 60 percent of resting OC and the mass of several internal organs, especially liver and gastrointestinal tract, are rapidly decreased with ER. Without accounting for the internal organs, it is impossible to determine from whole animal studies if ER causes a uniform decrease in OC by all body components. The goal of this proposed project is to determine the effect of ER on organ specific OC in adult rhesus monkeys. In this experiment, we plan to simultaneously measure whole animal and regional (hepatomesenteric bed, brain, and hindlimb) OC in catheterized monkeys living in calorimetry chambers. We predict that ER will result in a rapid and sustained decrease in hepatomesenteric bed OC, while smaller or no changes in OC will be obeserved in brain and hindlimb. In this study using unrestrained adult rhesus monkeys, there are three specific aims:
Specific Aim 1 is to adapt current systems for measuring regional (hepatomesenteric bed, brain, and hindlimb) and whole animal OC to allow simultaneous measurement of whole animal and regional OC.
Specific Aim 2 is to determine the contribution of organ and regional OC to whole animal OC.
Specific Aim 3 is to determine the effect of a 30 percent ER on OC by the hepatomesenteric bed, brain, and hindlimb. This study will provide important new information about the effect of ER on regional OC in an adult primate. The proposed methods may ultimately be used to determine if long-term ER causes a uniform reduction in tissue OC.
| Ramsey, J J; Colman, R J; Binkley, N C et al. (2000) Dietary restriction and aging in rhesus monkeys: the University of Wisconsin study. Exp Gerontol 35:1131-49 |
| Ramsey, J J; Harper, M E; Weindruch, R (2000) Restriction of energy intake, energy expenditure, and aging. Free Radic Biol Med 29:946-68 |
