GDF11 Treatment Attenuates the Recovery of Skeletal Muscle Function After Injury in Older Rats

AAPS J. 2017 Mar;19(2):431-437. doi: 10.1208/s12248-016-0024-x. Epub 2016 Dec 6.

Abstract

Loss of skeletal muscle mass and function results in loss of mobility for elderly patients. Novel therapies that can protect and/or restore muscle function during aging would have profound effects on the quality of life for this population. Growth differentiation factor 11 (GDF11) has been proposed as a "youthful" circulating factor that can restore cardiac, neural, and skeletal muscle functions in aging animals. However, conflicting data has been recently published that casts doubt on these assertions. We used a complex rat model of skeletal muscle injury that physiologically mimics injuries seen in patients; to investigate the ability of GDF11 and to enhance skeletal muscle regeneration after injury in older rats. Our data showed that GDF11 treatment resulted in a significant increase in tissue fibrosis, accompanied by attenuated functional recovery, as compared to animals treated with vehicle alone. GDF11 impaired the recovery of skeletal muscle function in older rats after injury.

Keywords: GDF11; regeneration; sarcopenia; skeletal muscle.

MeSH terms

  • Aging / physiology*
  • Animals
  • Bone Morphogenetic Proteins / administration & dosage
  • Bone Morphogenetic Proteins / toxicity*
  • Disease Models, Animal
  • Fibrosis
  • Growth Differentiation Factors / administration & dosage
  • Growth Differentiation Factors / toxicity*
  • Humans
  • Male
  • Muscle, Skeletal / injuries
  • Muscle, Skeletal / metabolism*
  • Quality of Life
  • Rats
  • Rats, Inbred Lew
  • Regeneration / physiology*

Substances

  • Bone Morphogenetic Proteins
  • GDF11 protein, human
  • Growth Differentiation Factors