The protein GDF-11 has recently been shown to influence the decline in muscle stem cell function with aging and other aspects of aging in mice. Alterations in circulating levels of GDF-11 can restore stem cell activity in aged individuals, in at least some tissues, though there is the strong possibility that overriding this age-related reaction to rising levels of cellular damage may lead to cancer.
GDF-11 is related to myostatin, a protein shown to guide muscle growth. Loss of myostatin leads to very muscular individuals, and as is the case for for GDF-11 scientists are considering the development of treatments based on manipulating levels of this protein. Here researchers present more context for these overlapping mechanisms based on fly studies:
Using transgenic RNAi screening, we recently discovered several myokines that regulate lifespan and muscle aging in the fruit fly Drosophila melanogaster. Among the myokines regulating the lifespan of Drosophila, we found Myoglianin, a TGF-beta ligand expressed primarily by skeletal muscle and glia. Drosophila Myoglianin is homologous to human GDF11 and Myostatin (GDF8), two highly related TGF-beta ligands that circulate in the bloodstream in mammals.
We found that Drosophila Myostatin (Myoglianin) extends lifespan and delays systemic aging by acting on muscle, adipocytes, and possibly other tissues. These effects were not due to feeding or changes in muscle mass, suggesting that Drosophila may be a convenient system for testing the direct signaling roles of Myostatin without the indirect confounding effects deriving from the increased muscle mass observed in Myostatin knock-out mice. In fact, these mice have increased insulin sensitivity and decreased adiposity due to higher nutrient utilization in muscle (and consequent reduced nutrient availability for other tissues) deriving from the doubling in muscle mass, which is a prominent feature of Myostatin knock-out mice.
In addition to Myostatin, Myoglianin is homologous to the related factor GDF11. A previous study in mice showed that GDF11 levels decline during aging and that this contributes to developing age-related cardiac hypertrophy. The finding that the GDF11 homolog Myoglianin preserves muscle function during aging in Drosophila suggests that GDF11 may also have anti-aging effects on tissues other than the heart. Indeed very recent studies have shown that GDF11 delays skeletal muscle and brain aging in mice, suggesting that GDF11 is an evolutionarily conserved, general regulator of tissue aging.