The Latest on the Debate Over GDF-11 Findings

Resulting from parabiosis studies in mice, GDF-11 is one of the significant proteins identified to vary with age in blood. When augmented to youthful levels in old mice it produces partial reversal of some measures of degeneration via boosted stem cell activity. The underlying mechanisms for these findings were disputed, however, and here is the latest in that discussion:

Back in the 1950s scientists first showed that connecting the circulatory systems of old and young mice seems to rejuvenate the more elderly animals. A handful of labs have recently been racing to find factors in young blood that may explain this effect. Researchers claim that a specific protein, GDF11, may explain young blood's beneficial effects. They have reported that blood levels of GDF11 drop in mice as the animals get older and that injecting old mice with GDF11 can partially reverse age-related thickening of the heart.

Last May, however, another group reported that the antibody the Harvard team used to measure levels of GDF11 also detected myostatin (also known as GDF8), a similar protein that hinders muscle growth. This group concluded from a different assay that GDF11 levels in blood actually rise with age in rats and people. And in their lab, GDF11 injections inhibited muscle regeneration in young mice. Now, the original researchers say that this assay used to detect GDF11 and GDF8 was itself flawed. They found that the main protein detected by the antibody test is immunoglobulin, another protein that rises in blood level with age. Mice lacking the gene for immunoglobulin tested negative for the active form of GDF11/8 that the assay was thought to reveal. "They actually had very consistent findings to ours with respect to the blood levels of GDF11/8 with the antibody we all used, but their interpretation was confused by this case of mistaken identity."

A recently published study finding that GDF11/8 blood levels decline with age in people and are low in those with heart disease supports the contention that GDF11 has an antiaging role. To back up their earlier results, the original researchers again show in a new paper that daily GDF11 injections can shrink heart muscle in both old and new mice. But this time they note another observation: The mice also lost weight. "We don't have much insight into that right now, but we're looking into it." The findings suggest that as with other hormones, GDF11 may have "a therapeutic window" for beneficial effects - too much may cause harm.