More Insight Into GDF-11 and Myostatin From Fly Studies

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.



It is a common tendency to look for magic bullets to cure what ails us, but research into GDF11 really is interesting so far.

Whenever I read articles regarding such things as Harvard research into telomerase knock-out mice or GDF11 effects from infusion, I have to consider confounders and unintended consequences, so simpler studies of Drosophila melanogaster lend weight to the conclusion that GDF11 really does extend lifespan and affect more than muscle development.

A few questions arise, however. Why does GDF11 synthesis decline with age in humans? Does it decline more slowly in some? If so, what lifestyle, genetic, or environmental factors play a role in slowing the decline? Are there foods or supplements that act as co-factors to support naturally high (or higher than average) levels of GDF11? If a young mouse with poor health and nutrition was injected with GDF11, would it alter the course of disease, general metabolism, and/or physical/cognitive performance? If not, what deficiencies (amino acids, enzymes, minerals, etc.) might be preventing GDF11 from being most effective for that animal?

In healthy mice injected with GDF11, is any effect on telomere length noted? How does the presence of added GDF11 affect cancer or tumor growth? Is it carcinogenic in and of itself? If so, what protects those animals who do not develop cancer when repeatedly dosed with GDF11? How does GDF11 influence genetic expression, oxidative stress, and synthesis of other vital proteins?

I'm sure there are numerous other important questions to add to this list, and as an educated non-scientist, I'm sure some of these questions could be worded more relevantly for the research scientists in our midst. Nonetheless, I hope to see answers to these and many other questions regarding anti-aging factors in years to come.

Posted by: Lon at May 24th, 2014 9:53 AM

Two Teams of scientists at Harvard University showed that blood or plasma from young mice reverses aging in old mice, regenerate their hearts, muscles and brains.

One substance in the blood GDF11 was one of the chemicals that assisted in this endeavor. This chemical also exists in people. The hope is that young human blood will do the same for people.

It would be a good idea to allow a few people who must get long - term blood transfusions to get the blood only from young people as that may help with the rejuvenation process. A research project should be undertaken.

Before entering this research program the patients should receive non – invasive
tests and blood tests so that the improvements can be documented. Since the patients need the blood anyway why not give them the opportunity to participate in a program that can increase their health beyond what usually happens with blood transfusions from people of all ages? Of course, the patients will sign a form permitting this.

Young college students will be willing to donate blood and there is blood on the market for them to use. Some institutions can exchange blood from older blood donators for younger blood donors.

If blood transfusion patients get blood or plasma from old patients it can negatively influence their health as the mice experiments have shown. The research suggested here will help answer that question. At the same time, it will be an excuse to see if the regeneration takes place.

There is no FDA approval necessary, as it is just a blood or plasma transfusion.

Using GDF 11 on chimpanzees, other primates or higher mammals was done yet. It may give us surprising results. It should also be tried on fowl, fish, etc. to see if old animals can have their life extended and also if regeneration takes place.

Non invasive tests can also be done.

Posted by: Alvin Steinberg at July 6th, 2014 4:40 PM

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