Shorter telomeres in dystrophic muscle consistent with extensive regeneration in young children
Shorter telomeres in dystrophic muscle consistent with extensive regeneration in young children
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DOI：
10.1016/s0960-8966(99)00093-0
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发表时间：
2000-02-01
影响因子：
2.8
通讯作者：
Butler-Browne, GS
中科院分区：
文献类型：
--
作者：
Decary, S;Ben Hamida, C;Butler-Browne, GS
肌营养不良的特点是不断的退化和再生循环，最终导致肌肉质量的减少和广泛的纤维化。在体细胞中，染色体端粒随着每一轮细胞分裂而缩短，端粒长度被认为是细胞复制历史的生物标志物。我们之前已经证明，人类成肌细胞的增殖能力有限，而正常骨骼肌的核周转水平非常低。然而，在患有肌肉营养不良的患者中，卫星细胞将被迫进行反复的细胞分裂，推动细胞走向衰老。在这项研究中，我们使用端粒长度来量化不同年龄营养不良患者活检中肌肉细胞周转的强度。我们的结果表明，一旦第一个临床症状变得明显，肌肉就已经经历了广泛的再生，端粒丢失的速度是对照组的14倍。这证实了再生能力的下降是由于卫星细胞在肌肉修复过程中过度增殖而导致的过早衰老。(C)2000 Elsevier Science B.V.保留所有权利。
Muscular dystrophies are characterised by continuous cycles of degeneration and regeneration resulting in an eventual diminution of the muscle mass and extensive fibrosis. In somatic cells chromosomal telomeres shorten with each round of cell division and telomere length is considered to be a biomarker of the replicative history of the cell. We have previously shown that human myoblasts have a limited proliferative capacity, and that normal skeletal muscle has a very low level of nuclear turnover. However, in patients suffering 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 the muscle cell turnover in biopsies from dystrophic patients of different ages. Our results show that as soon as the first clinical symptoms become apparent 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.