Dietary intake of GDF11 delays the onset of several biomarkers of aging in male mice through anti-oxidant system via Smad2/3 pathway

Current studies have generated controversy over the age-related change in concentration of growth differentiation factor 11 (GDF11) and its role in the genesis of rejuvenation conditions. In this study, we displayed rGDF11 on the surface of Yarrowic Lipolytica (Y. lipolytica), and proved the bioavailability of the yeast-displayed rGDF11 by oral delivery in aged male mice. On the basis of these findings, we started to explore the anti-aging activity and underlying mechanisms of displayed rGDF11. It was found that dietary intake of displayed rGDF11 had little influence on the body weight and biochemical parameters of aged male mice, but delayed the occurrence and development of age-related biomarkers such as lipofuscin (LF) and senescence-associated-β-galactosidase, and to some extent, prolonged the lifespan of aged male mice. Moreover, we demonstrated once again that dietary intake of displayed rGDF11 enhanced the activity of anti-oxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPX), reduced the reactive oxygen species (ROS) level, and slowed down the protein oxidation and lipid peroxidation. Importantly, we showed for the first time that rGDF11 enhanced the activity of CAT, SOD and GPX through activation of the Smad2/3 signaling pathway. Our study also provided a simple and safe route for delivery of recombinant GDF11, facilitating its therapeutic application in the future. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s10522-022-09967-w.