Resveratrol does not mimic the positive effects of calorie restriction on lifespan in Microcebus murinus

Resveratrol (RSV), a polyphenol with anti-aging properties affecting metabolism and energy balance, is considered as a mimetic candidate to calorie restriction (CR). However its potential effects on delaying the onset of age-related diseases and increasing longevity have not yet been demonstrated in non-obese models close to humans such as non-human primates. The longitudinal monitoring of cognitive and motor performances, occurrence of age-related pathologies, age-related brain atrophy and mortality was performed from adulthood to death in a cohort of male grey mouse lemurs (Microcebus murinus, N = 33), all receiving 105 kJ/day of food but with a subset of 18 animals receiving RSV (200 mg.kg^-1 body weight.day^-1). RSV supplementation improved cognitive and motor performance at middle age as compared to control (CTL) animals. Median-lifespan was greater in RSV-fed animals (7.9 years compared to 6.4 years for CTL) but long-term RSV supplementation did not significantly affect all-cause nor age-related mortality. Also, brain grey matter atrophy accelerated in the RSV group at old age as compared to the CTL group. Altogether, these results suggest that long-term RSV supplementation procures health benefits at middle-age in male mouse lemurs but has limited long-term effects on health and longevity and might even impair brain integrity at older ages.