AUTHOR=Kiriaev Leonit , Kueh Sindy , Morley John W. , North Kathryn N. , Houweling Peter J. , Head Stewart I. 

TITLE=Lifespan Analysis of Dystrophic mdx Fast-Twitch Muscle Morphology and Its Impact on Contractile Function

JOURNAL=Frontiers in Physiology

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.771499

DOI=10.3389/fphys.2021.771499

ISSN=1664-042X

ABSTRACT=Duchenne muscular dystrophy is caused by the absence of the protein dystrophin from skeletal muscle and is characterized by progressive cycles of necrosis/regeneration. Using the dystrophin deficient mdx mouse model we studied the morphological and contractile chronology of dystrophic skeletal muscle pathology in fast-twitch EDL muscles from animals 4-22 months of age containing 100% regenerated muscle fibers. Catastrophically, the older age groups lost ~80% of their maximum force after one eccentric contraction of 20% strain, with the greatest loss ~93% recorded in senescent 22 month old mdx mice. In old age groups there was minimal force recovery ~24% after 120 minutes, correlated with a dramatic increase in the number and complexity of branched fibers. This data supports our two-phase model where a “tipping point” is reached when branched fibers rupture irrevocably on eccentric contraction. These findings have important implications for pre-clinical drug studies and genetic rescue strategies.