Calorie restriction and resveratrol supplementation prevent age-related DNA and RNA oxidative damage in a non-human primate

Abstract

Oxidative stress is a key factor in the aging process and in the development of age-related diseases. Because nutritional interventions such as caloric restriction (CR) delay the onset of age-related diseases and increase the lifespan of many species, the impact of a moderate CR was tested on male grey mouse lemur (Microcebus murinus), which have a median survival time of 5.7years in captivity. The effects of CR on these lemurs were compared with a potential mimetic, resveratrol (RSV), a polyphenol naturally found in grapes. We hypothesized that both CR and RSV impact oxidative DNA and RNA damage compared to standard-fed control (CTL) animals. Adult (3–4years old) male mouse lemurs were assigned to three dietary groups: a CTL group, a CR group receiving 30% fewer calories than the CTL and a RSV group receiving the CTL diet supplemented with RSV (200mg·day−1·kg−1). Oxidative stress was estimated after 3, 9, 15 and 21months of treatment using the measurement of oxidized nucleosides in urine samples by mass spectrometry. The resting metabolic rate, adjusted for changes in body composition, was also measured to assess the potential relationship between oxygen consumption and oxidative damage markers. This study provides evidence for oxidative stress accumulation with age in grey mouse lemur. Dietary interventions resulted in a short-term increase in oxidative stress levels followed by reduced levels with increasing age. Moreover, in this photoperiod-dependent heterotherm primate, seasonal variations in oxidative stress were observed, which was likely due to a season-dependent, cost–benefit trade-off between torpor use and oxidative stress.