Did GDF11 really improve muscle regeneration?

In parabiosis experiments, the blood of younger mice seems to rejuvenate the muscles of older mice. In 2013, Dr. Amy Wagers, a biologist at Harvard University, seemed to offer an explanation for this effect. Wagers identified a protein called GDF11 as a circulating factor in young mice that declines with age.[1]. Injection of GDF11 reversed age-related thickening of the heart.

Two subsequent studies found that GDF11 improved blood vessel and neuron growth in the brain[2] and reversed age-related dysfunction in skeletal muscle[3]. GDF11 appeared to be one of the key components of the young blood.

However, some experts were confused by Wagers’ papers, because GDF11 is very similar to myostatin, a negative regulator of muscle growth. Myostatin knockout mice have approximately twice as much muscle as normal mice[4]. Could a very similar protein have the opposite effect?

As early as 2009, Dr. David Glass at the Novartis Institutes for BioMedical Research showed that GDF11 could inhibit muscle growth[5]. Who is right?

Glass tested GDF11 levels in rats with the assays Wagers had used and found that Wagers’ assays could not distinguish between the monomer and dimer forms of GDF11 as well as myostatin[6]. GDF11 levels actually did not decrease with age. Injecting GDF11 into mouse muscle did not improve muscle regeneration.

Antibodies are among the most commonly used tools to detect target proteins. However, they are a major driver of reproducibility crisis[7]. Commercial antibodies often recognize extra proteins in addition to the ones they are sold to detect. We need to have some changes in the field.

[1] Cell. 2013, 153 (4), 828-839.
[2] Science. 2014, 344(6184), 630-634.
[3] Science. 2014, 344(6184), 649-652.
[4] Nature. 1997, 387(6628), 83-90.
[5] Am J Physiol Cell Physiol. 2009, 296(6), C1258-1270.
[6] Cell Metab. 2015, doi:10.1016/j.cmet.2015.05.010.
[7] Nature. 2015, 521, 274-276.

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