The path of scientific discovery is never direct, and if something appears simple in an investigation of biochemistry then it is perhaps time to wonder what was missed and when the other shoe will drop. In the past couple of years researchers have demonstrated improved health in aged mice through reactivation of stem cell activity via increased levels of GDF-11. The situation may well be more complex than first thought, however, as a second group is having issues replicating the effect. This work calls into question present hypotheses on the nature of the underlying mechanisms exhibited in previous work on GDF-11, and points to the need for a better and more complete analysis of what is going on under the hood. The observed improvements to health seen in past studies are not yet disputed, but clearly something is missing:
In 2013, a team found that levels of a protein called GDF11 decreased in the blood of mice as they grew older. When the researchers injected the protein into the heart muscle of old mice, it became 'younger' - thinner and better able to pump blood. Two subsequent studies found that GDF11 boosted the growth of new blood vessels and neurons in the brain and spurred stem cells to regenerate skeletal muscle at the sites of injuries. Those results quickly made GDF11 the leading explanation for the rejuvenating effects of transfusing young blood into old animals. But that idea was confusing to many because GDF11 is very similar to the protein myostatin, which prevents muscle stem cells from differentiating into mature muscle - the opposite effect to that seen.
Researchers set out to determine why GDF11 had this apparent effect. First, they tested the antibodies and other reagents used to measure GDF11 levels, and found that these chemicals could not distinguish between myostatin and GDF11. When the team used a more specific reagent to measure GDF11 levels in the blood of both rats and humans, they found that GDF11 levels actually increased with age - just as levels of myostatin do. That contradicts what the former group had found. The researchers next used a combination of chemicals to injure a mouse's skeletal muscles, and then regularly injected the animal with three times as much GDF11 as the former team had used. Rather than regenerating the muscle, GDF11 seemed to make the damage worse by inhibiting the muscles' ability to repair themselves.
Researchers suggest that there could be multiple forms of GDF11 and that perhaps only one decreases with age. Both papers suggest that having either too much or too little GDF11 could be harmful. The more recent research group injured the muscle more extensively and then treated it with more GDF11 than the former group had done, so the results may not be directly comparable. "We look forward to addressing the differences in the studies with additional data very soon."