Administration of rGDF11 retards the aging process in male mice via action of anti-oxidant system.

ABSTRACT

One of the most studied and widely accepted conjectures of aging process is the oxidative stress theory. Current studies have generated disputes on the effects of GDF11 and GDF8, a closely related member of GDF11, on rejuvenation and anti-aging properties. In this study, we first demonstrated that when recombinant GDF8 (rGDF8) and GDF11 (rGDF11) of the fish Nothobranchius guentheri were injected into 20-month-old male mice, their serum GDF8 and GDF11 levels were clearly increased. We also showed that injection of rGDF8 and rGDF11 had little influences on the body weight and serological parameters of the mice, indicating their general condition and physiology were not affected. Based on these findings, we started to test the effects of administration of piscine rGDF11 and rGDF8 on the aging process of male mice and to explore the underlying mechanisms. It was found that rGDF11 was able to reduce the levels of AGEs, protein oxidation and lipid peroxidation, and to slow down the accumulation of age-related histological markers, while rGDF8 was not. Moreover, rGDF11 significantly prevented the decrease in CAT, GPX and SOD activities, but rGDF8 did not. Collectively, these results suggest that it is GDF11 but not GDF8 that can exert rejuvenation and anti-aging activities via the action of antioxidant system. It is also the first report that shows the activity of GDF11 is not species-specific, implicating potential usefulness of piscine GDF11 in prolonging the lifespan of the elderly.