Short-term moderate caloric restriction in the rhesus macaque attenuates markers of ovarian aging in select populations.

Ovarian aging results in decreased fertility and endocrine function. In mice, caloric restriction (CR) maintains ovarian function. In this study, we determined whether CR also has a beneficial effect on reproductive longevity in the nonhuman primate (NHP). Ovaries were collected from young (10-13 years) and old (19-26 years) rhesus macaques who were either on a diet of moderate caloric restriction or a control diet for three years. To test the effect of CR on follicle number, follicles were analyzed in histological sections from animals across experimental cohorts: Young Control, Young CR, Old Control, Old CR (n = 4-8/group). In control animals, there was an age-dependent decrease in follicle numbers across all follicle stages (P < 0.05). Although there was no effect of diet on total follicle number, the follicle distribution in the Old CR cohort more closely resembled that of young animals. The subset of Old CR animals that were still cycling, albeit irregularly, had more primordial follicles than controls (P < 0.05). Assessment of collagen and hyaluronic acid matrices revealed that CR attenuated age-related changes to the ovarian microenvironment. Overall, CR may improve aspects of reproductive longevity in the NHP, but the timing of when it occurs during the reproductive lifespan is likely critical.