Update on GDF11 controversy

by Alexey Bersenev on April 3, 2016 · 0 comments

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The controversy around “anti-aging circulating factor” GDF11 continue to unfold. Just to remind you, “high profile” study by Harvard’s Amy Wagers group, described GDF11 as “rejuvenating circulating factor”, which reversed functional impairment of aged muscle stem cells. Another study, performed in collaboration with Wager’s lab, demonstrated that increase of GDF11 level led to reversal of age-related cardiac hypertrophy. Intriguingly, findings from both studies were challenged and disputed by other academic researchers and by industry companies (read here and here). Here are some of studies, which were not able to reproduce Wager’s results:
David Glass, Cell Metabolism 2015
Steven Houser, Circulation Research 2015
Rodgers and Eldridge, Endocrinology 2015

The most recent reproducibility study, performed by GSK, just came up in Aging Cell and concluded:

We have been unable to confirm the reported activity of GDF11, similar to other laboratories offering conflicting data and describe our attempts to do so…

The authors attempted to reproduce only one part of Wager’s study. They used exactly the same cell culture conditions to find out effect of GDF11 on muscle stem cells:

The data we obtained using the culture system of Sinha et al. are most consistent with that presented by Egerman et al., at least with regard to the effects of rGDF11 on young SCs. In addition, we tested for the effects of both GDF8 and GDF11 on lean mass in young mice via expression in the liver by injection of expression plasmids containing GDF8 or GDF11 cDNA. Lean mass in these mice was reduced over a period of 7 days (Fig. 1C). These data are consistent with the fact that GDF11 shares a high degree of sequence identity with GDF8, activates similar signaling pathways (Lach-Trifilieff et al., 2014), does not promote SC outgrowth, and reduces lean mass in mice. Thus in these findings, GDF11 exhibits activity similar to that of GDF8. Clearly, further investigation is needed to fully clarify whether, and under what, if any, conditions GDF11 is a factor that beneficially regulates muscle activity during aging.

This is the second industry study (after Novartis), which was not able to reproduce Wager’s experiments and support claims about GDF11 as anti-aging factor. I was glad to see that conventional journals are willing to publish reproducibility studies with negative finding. I was also glad to see that analogously to cancer research, industry is willing to publish their reproducibility efforts in stem cell field.

Since beginning of the controversy, Wagers and Lee published one more clarifying report on GDF11, where highlighted the difference in antibodies as the major reason for lack of reproducibility. However, different results from other experiments were not explained by Wagers. Discussion between Wagers and Houser continued in Circulation Research here and here. Also read discussion on PubPeer.

I’m watching this controversy with great interest. All groups stand for their data. To me, the controversy could be resolved through setting up a parallel experiment with the same antibody lot. As of now, nobody was able to reproduce (as far as I know) findings from Harvard labs.

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