The role of GDF11 in aging and skeletal muscle, cardiac and bone homeostasis

Abstract

GDF11 is a secreted factor in the TGFß family of cytokines. Its nearest neighbor evolutionarily is myostatin, a factor discovered as being a negative regulator of skeletal muscle growth. High profile studies several years ago suggested that GDF11 declines with age, and that restoration of systemic GDF11 to ‘youthful’ levels is beneficial for several age-related conditions. Particularly surprising was a report that supplementation of GDF11 aided skeletal muscle regeneration, as its homolog, myostatin, has the opposite role. Given this apparent contradiction in functionality, multiple independent labs sought to discern differences between the two factors and better elucidate age-related changes in circulating GDF11, with most failing to reproduce the initial finding of declining GDF11 levels, and, importantly, all subsequent studies examining the effects of GDF11 on skeletal muscle described an inhibitory effect on regeneration – and that higher doses induce skeletal muscle atrophy and cachexia. There have also been several studies examining the effect of GDF11 and/or the downstream ActRII pathway on cardiac function, along with several interesting reports on bone. A review of the GDF11 literature, as it relates in particular to aging and skeletal muscle, cardiac and bone biology, is presented.

Keywords:

• Skeletal muscle
• aging
• myostatin
• GDF11
• bone
• heart
• cardiac muscle

Acknowledgements

The authors thank the Age-Related Disorders group, as part of the Chemical Biology and Therapeutics Group, at the Novartis Institutes for Biomedical Research for their help and support. The authors also thank Nathan LeBrasseur for reading the manuscript and giving comments.

Disclosure statement

D.J.G. is a current employee of the Novartis Institutes for Biomedical Research. D.J.G. is a stockholder in Novartis. M.A.E. declares no conflicts of interest.