Aging increases the susceptibility of skeletal muscle derived satellite cells to apoptosis
Aging increases the susceptibility of skeletal muscle derived satellite cells to apoptosis
复制标题
DOI：
10.1016/j.exger.2006.06.053
复制
发表时间：
2006-09-01
影响因子：
3.9
通讯作者：
Kuzon, William M., Jr.
中科院分区：
文献类型：
--
作者：
Jejurikar, Sameer S.;Henkelman, Erika A.;Kuzon, William M., Jr.
引起老年动物骨骼肌损伤再生反应受损的机制尚不清楚。卫星细胞，成人骨骼肌内的干细胞后代，是再生肌纤维的主要来源。细胞凋亡可能是老年动物卫星细胞耗竭的一种机制。这项工作验证了衰老增加卫星细胞凋亡易感性的假设。卫星细胞分别取自幼龄（3月龄）、成年（9月龄）和老年（31月龄）褐挪威大鼠的指长伸肌。用促凋亡剂tnf - α (20 ng/mL)和放线菌素D （250 ng/mL）处理卫星细胞24 h。采用活化的半胱天冬酶和末端脱氧核苷酸转移酶介导的dutp镍端标记（TUNEL）免疫染色来鉴定凋亡卫星细胞。Western blot法检测抗凋亡蛋白bcl-2的表达量。与年轻动物和成年动物相比，老年动物的卫星细胞具有活化的半胱天冬酶和tunel阳性细胞的比例显著提高，bcl-2的含量显著降低。这些数据支持了衰老增加卫星细胞凋亡易感性的假设。在衰老肌肉中，细胞凋亡可能在卫星细胞的耗竭中起导致作用，损害对损伤的再生反应。Elsevier Inc.出版。
The mechanisms causing the impaired regenerative response to injury observed in skeletal muscle of old animals are unknown. Satellite cells, stem cell descendants within adult skeletal muscle, are the primary source of regenerating muscle fibers. Apoptosis may be a mechanism responsible for the depletion of satellite cells in old animals. This work tested the hypothesis that aging increases the susceptibility of satellite cells to apoptosis. Satellite cells were cultured from the extensor digitorum longus muscles of young (3-month-old), adult (9-month-old), and old (31-month-old) Brown Norway rats. Satellite cells were treated for 24 h with the pro-apoptotic agents TNF-alpha (20 ng/mL) and Actinomycin D (250 ng/mL). Immunostaining for activated caspases and terminal deoxynucleotydil transferase-mediated dutp nick-end labeling (TUNEL) was performed to identify apoptotic satellite cells. Quantity of the anti-apoptotic protein bcl-2 was determined by Western blot analysis. Satellite cells from old animals demonstrated significantly higher percentages of cells with activated caspases and TUNEL-positive cells, and significantly lower amounts of bcl-2 compared to young and adult animals. These data support the hypothesis that aging increases satellite cell susceptibility to apoptosis. In old muscle, apoptosis may play a causative role in the depletion of satellite cells, impairing the regenerative response to injury. Published by Elsevier Inc.