Examination of telomere lengths in muscle tissue casts doubt on replicative aging as cause of progression in Duchenne muscular dystrophy.

The mean telomere length (TL) of somatic cells indicates their replicative age. In comparison with normal leukocytes (-0.03 kbp/y, 6.2 kbp at 80 y), we found advanced TL shortening in premature aging due to ataxia-telangiectasia or the Nijmegen chromosomal breakage syndrome. Duchenne muscular dystrophy (DMD) has been related to replicative senescence of satellite cells (SCs) caused by increased fiber turnover. Therefore, we determined TLs in DMD muscle. Because the regenerated fiber nuclei are produced by SCs. telomeres of both fiber and SC nuclei should be shortened. In DMD the SC number is increased. We determined that up to the age of 7 y the sum of fiber and SC nuclei should be large enough (73%) for the detection of TL shortening. Normal muscle fibers have negligible turnover rates, and, as expected, we did not find age-related TL shortening (10-83 y, n = 24, 8.3 +/- 0.5 kbp). Surprisingly, there was only slight TL shortening in patient muscles (DMD, 0.3-4.8 y, n = 4, 8.3 +/- 0.7 kbp; 5-7 y, n = 7, 7.9 +/- 0.4 kbp; limb-girdle muscular dystrophy 2C, 13 y, 7.6 kbp; Becker muscular dystrophy, 7 y, 8.5 kbp). Similarly, the peak positions of the telomere blots varied only slightly (DMD, 10.0 +/- 0.9 kbp; normal: 10.7 +/- 0.9 kbp). In accordance with our TL findings we derived less than 4 annual doublings per SC from published histologic data on DMD.