Supraphysiologic Administration of GDF11 Induces Cachexia in Part by Upregulating GDF15

Citations of this article
Mendeley users who have this article in their library.


The age-related effects of GDF11 have been a subject of controversy. Here, we find that elevated GDF11 causes signs of cachexia in mice: reduced food intake, body weight, and muscle mass. GDF11 also elicited a significant elevation in plasma Activin A, previously shown to contribute to the loss of skeletal muscle. The effects of GDF11 on skeletal muscle could be reversed by administration of antibodies to the Activin type II receptors. In addition to the effects on muscle, GDF11 increased plasma GDF15, an anorectic agent. The anorexia, but not the muscle loss, could be reversed with a GDF15-neutralizing antibody. GDF15 upregulation is due to GDF11-induced recruitment of SMAD2/3 to the GDF15 promoter. Inhibition of GDF15 can restore appetite but cannot restore the GDF11-induced loss of muscle mass, which requires blockade of ActRII signaling. These findings are relevant for treatment of cachexia. Jones et al. find that high levels of GDF11 in mice induce symptoms of cachexia: skeletal muscle loss and anorexia. The anorexia is due to GDF11-dependent upregulation of GDF15. Downregulation of GDF11 in settings in which it exists at high levels is predicted to be beneficial.




Jones, J. E., Cadena, S. M., Gong, C., Wang, X., Chen, Z., Wang, S. X., … Glass, D. J. (2018). Supraphysiologic Administration of GDF11 Induces Cachexia in Part by Upregulating GDF15. Cell Reports, 22(6), 1522–1530.

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free