Calorie Restriction Improves Measures of Ovarian Aging in Non-Human Primates
Calorie restriction is well known to slow aging in mammals. Short-term improvements in metabolism are fairly similar across mammalian species, but short-lived mammals show a much greater extension of life span in response to calorie restriction than is the case in long-lived mammals such as our own species. Why this is the case remains to be determined, but one might suspect that the answer lies somewhere in the still incompletely cataloged details of autophagy - how exactly autophagy changes with age, and how exactly autophagy differs between species. Researchers have demonstrated that the cellular maintenance processes of autophagy are required to function correctly in order for a slowing of aging to result from calorie restriction, making it the first place to look.
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. 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. 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.