Lund Troy C, Grange Robert W, Lowe Dawn A
Pediatric Hematology-Oncology and Blood and Marrow Transplant Program, University of Minnesota, School of Medicine, Minneapolis, Minnesota 55455, USA.
Muscle Nerve. 2007 Sep;36(3):387-90. doi: 10.1002/mus.20824.
The progression of Duchenne muscular dystrophy (DMD) is, in part, due to satellite cell senescence driven by high replicative pressure as these muscle stem cells repeatedly divide and fuse to damaged muscle fibers. We hypothesize that telomere shortening in satellite cells underlies their senescence. To test this hypothesis, we evaluated the diaphragm and a leg muscle from dystrophic mice of various ages for telomere dynamics. We found 30% telomere shortening in tibialis anterior muscles from 600-day-old mdx mice relative to age-matched wildtype mice. We also found a more severe shortening of telomere length in diaphragm muscles of old mdx mice. In those muscles, telomeres were shortened by approximately 15% and 40% in 100- and 600-day-old mdx mice, respectively. These findings indicate that satellite cells undergo telomere erosion, which may contribute to the inability of these cells to perpetually repair DMD muscle.
杜兴氏肌肉营养不良症（DMD）的病情进展部分归因于卫星细胞衰老，这种衰老是由高复制压力驱动的，因为这些肌肉干细胞会反复分裂并与受损的肌纤维融合。我们假设卫星细胞中的端粒缩短是其衰老的基础。为了验证这一假设，我们评估了不同年龄的营养不良小鼠的膈肌和腿部肌肉的端粒动态变化。我们发现，600日龄的mdx小鼠胫前肌的端粒相对于年龄匹配的野生型小鼠缩短了30%。我们还发现，老年mdx小鼠膈肌的端粒长度缩短更为严重。在这些肌肉中，100日龄和600日龄的mdx小鼠的端粒分别缩短了约15%和40%。这些发现表明卫星细胞会发生端粒侵蚀，这可能导致这些细胞无法永久性修复DMD肌肉。
