Shorter telomeres in dystrophic muscle consistent with extensive regeneration in young children

Muscular dystrophies are characterised by continuous cycles of degeneration and regeneration resulting in an eventual diminution of the muscle mass an d extensive fibrosis. In somatic cells chromosomal telomeres shorten with e ach round of cell division and telomere length is considered to be a biomar ker of the replicative history of the cell. We have previously shown that h uman myoblasts have a limited proliferative capacity, and that normal skele tal muscle has a very low level of nuclear turnover. However, in patients s uffering from muscular dystrophy the satellite cells will be forced to make repeated rounds of cell division, driving the cells towards senescence. In this study we have used the telomere length to quantify the intensity of t he muscle cell turnover in biopsies from dystrophic patients of different a ges. Our results show that as soon as the first clinical symptoms become ap parent the muscle has already undergone extensive regeneration and the rate of telomere loss is 14 times greater than that observed in controls. This confirms that the decline in regenerative capacity is due to the premature senescence of the satellite cells induced by their excessive proliferation during muscle repair. (C) 2000 Elsevier Science B.V. All rights reserved.