GDF11

5E4G1022014561ENSG00000135414ENSMUSG00000025352O95390Q9Z1W4NM_005811NM_010272NP_005802NP_034402Growth differentiation factor 11 (GDF11) also known as bone morphogenetic protein 11 (BMP-11) is a protein that in humans is encoded by the growth differentiation factor 11 gene. Growth differentiation factor 11 (GDF11) also known as bone morphogenetic protein 11 (BMP-11) is a protein that in humans is encoded by the growth differentiation factor 11 gene. GDF11 acts as a cytokine and its molecular structure is identical in humans, mice and rats.The bone morphogenetic protein group is characterized by a polybasic proteolytic processing site, which is cleaved to produce a protein containing seven conserved cysteine residues. Systemic GDF11 treatment improves vasculature in the hippocampus and cortex of old mice resulting in enhanced neurogenesis. Also, systematic replenishment of GDF11 improved the survival and morphology of β-cells and improved glucose metabolism in both non genetic and genetic mouse models of type 2 diabetes. GDF11 is a regulator of skin biology and has significant effects on the production of procollagen I and hyaluronic acid. GDF11 also activates the Smad2/3 phosphorylation pathway in skin endothelial cells and improves skin vasculature. Supplementation of systemic GDF11 levels, which normally decline with age, by heterochronic parabiosis or systemic delivery of recombinant protein, reversed functional impairments and restored genomic integrity in aged muscle stem cells (satellite cells). Increased GDF11 levels in aged mice also improved muscle structural and functional features and increased strength and endurance exercise capacity. Treatment of old mice to restore GDF11 to youthful levels recapitulated the effects of parabiosis and reversed age-related hypertrophy, revealing a therapeutic opportunity for cardiac aging. GDF11 has been found to reduce oxidative stress and was able to reduce the levels of AGEs, protein oxidation and lipid peroxidation, and to slow down the accumulation of age-related histological markers. GDF11 significantly prevented the decrease in CAT, GPX and SOD activities, Enhanced GDF11 expression promoted apoptosis and down-regulated GDF11 expression inhibited apoptosis in pancreatic cancer cell lines. These findings suggested that GDF11 acted as a tumor suppressor for pancreatic cancer. In 2014, GDF11 was described as a life extension factor in two publications based on the results of a parabiosis experiments with mice that were chosen as Science's scientific breakthrough of the year. Later studies questioned these findings. Researchers disagree on the selectivity of the tests used to measure GDF11 and on the activity of GDF11 from various commercially available sources. The full relationship of GDF11 to aging—and any possible differences in the action of GDF11 in mice, rats, and humans—is unclear and continues to be researched.