Effect of exercise on telomere length and telomere proteins expression in mdx mice

Mol Cell Biochem. 2020 Jul;470(1-2):189-197. doi: 10.1007/s11010-020-03761-3. Epub 2020 May 23.

Abstract

In Duchenne muscular dystrophy (DMD), telomere shortening has been postulated to contribute to the failure of regenerative activity promoting the premature senescence of satellite cells. The aim of the present study was to investigate the telomere length and the expression of telomeric repeat-binding factor-1 (TRF1), poly (ADP-ribose) polymerase-1 (PARP1) and mouse telomerase reverse transcriptase (MTERT) in gastrocnemius, tibialis anterior and diaphragm muscles of the murine model of DMD, the mdx mouse and whether a chronic protocol of forced exercise impacts on them. Our results confirmed a telomere shortening in mdx muscles, more evident in the diaphragm, in which exercise induced a greater shortening than in wild-type mice. Moreover, we showed for the first time in mdx an increased TRF1 and PARP1 expression and an augmented activity of MTERT, further enhanced by exercise. These results reinforce the hypothesis that a deregulation of mechanisms involved in telomere length occurs and may pave the way for the test of compounds targeting proteins modulating telomere maintenance as a novel strategy to treat dystrophinopathies.

Keywords: Exercise; Mdx; PARP1; TERT; TRF1; Telomere length.

MeSH terms

  • Animals
  • Disease Models, Animal
  • Genotype
  • Mice
  • Mice, Inbred mdx
  • Muscle, Skeletal / metabolism
  • Muscular Dystrophy, Duchenne / metabolism*
  • Physical Conditioning, Animal*
  • Poly (ADP-Ribose) Polymerase-1 / genetics*
  • Signal Transduction
  • Telomerase / genetics*
  • Telomere / metabolism*
  • Telomere Shortening
  • Telomeric Repeat Binding Protein 1 / genetics*

Substances

  • Telomeric Repeat Binding Protein 1
  • Parp1 protein, mouse
  • Poly (ADP-Ribose) Polymerase-1
  • Telomerase
  • Tert protein, mouse