Murine myoblast migration: influence of replicative ageing and nutrition

Biogerontology. 2017 Dec;18(6):947-964. doi: 10.1007/s10522-017-9735-3. Epub 2017 Nov 7.


Cell migration is central to skeletal muscle repair following damage. Leucine and β-Hydroxy β-methylbutyric acid (HMB) are supplements consumed for recovery from muscle damaging exercise in humans, however, their impact on muscle cell migration with age is not yet understood. We hypothesised that replicatively aged ("aged"; P46-P48) myoblasts would be less efficient at basal and supplemented repair versus parental controls ("control"; P12-P16). Aged and control myoblasts were scratch-damaged and migration velocity, directionality and distance assessed over 48 h in the absence and presence of leucine (10 mM) or HMB (10 mM) ± PI3K/Akt (LY294002 10 μM), ERK (PD98059 5 μM) or mTOR (rapamycin 0.5 μM) inhibition. Opposing our hypothesis, aged cells displayed increased velocities, directionality and distance migrated (P < 0.001) versus control. Leucine and HMB significantly increased (P < 0.001) the same parameters in control cells. The supplements were with smaller, albeit significant impact on aged cell velocity (P < 0.001) and in the presence of HMB only, distance (P = 0.041). Inhibitor studies revealed that, PI3K and ERK activation were essential for velocity, directionality and migration distance of aged cells in basal conditions, whereas mTOR was important for directionality only. While PI3K activation was critical for all parameters in control cells (P < 0.001), inhibition of ERK or mTOR improved, rather than reduced, control cell migration distance. Enhanced basal velocity, directionality and distance in aged cells required ERK and PI3K activation. By contrast, in control cells, basal migration was underpinned by PI3K activation, and facilitated by leucine or HMB supplementation, to migration levels seen in aged cells. These data suggest that replicatively aged myoblasts are not anabolically resistant per se, but are capable of efficient repair, underpinned by altered signaling pathways, compared with unaged control myoblasts.

Keywords: Ageing; Damage; ERK; HMB; Leucine; Myoblast; PI3K; mTOR.

MeSH terms

  • Animals
  • Cell Movement*
  • Cells, Cultured
  • Cellular Senescence*
  • Leucine / metabolism
  • Mice
  • Muscle, Skeletal / cytology*
  • Myoblasts / cytology*
  • Nutritional Status*
  • Signal Transduction
  • Valerates / metabolism


  • Valerates
  • beta-hydroxyisovaleric acid
  • Leucine