Dual role of the caspase enzymes in satellite cells from aged and young subjects.

Dual role of the caspase enzymes in satellite cells from aged and young subjects.
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DOI:
10.1038/cddis.2013.472
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发表时间:
2013-12-12
影响因子:
9
通讯作者:
--
中科院分区:
生物学1区
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--
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卫星细胞的增殖和分化在骨骼肌损伤后的恢复和对肥大刺激的适应中起着至关重要的作用。正常衰老阻碍了SC的增殖和分化,并与骨骼肌中许多促凋亡因子的表达增加有关。鉴于先前的研究表明,与SC抗氧化和修复活性有关的基因的表达与年龄有关,本研究旨在评估人SC中凋亡特征的发生率。取9名青年(2 7.3±2.0岁)和9名老年(71.1±1.8岁)股外侧肌原代细胞,分别于4、2 4、48、72 h在完全培养液中培养,用AnnexinV/碘化丙啶染色、末端脱氧核苷酸转移酶dUTP缺口末端标记技术、逆转录聚合酶链式反应、基因芯片、流式细胞仪和免疫荧光分析等方法检测细胞凋亡率。在所有实验时间点,老年受试者的细胞凋亡率均升高,AnnexinV阳性细胞与caspase-8活性之间没有直接关系。另一方面,CASP2、CASP6、CASP7、CASP9和一些细胞死亡基因在老年SCs中表达上调。总之,我们的数据显示,与年龄相关的人类干细胞对凋亡的敏感性增强,这可能是他们对肌肉损伤反应减弱的原因。
Satellite cell (SC) proliferation and differentiation have critical roles in skeletal muscle recovery after injury and adaptation in response to hypertrophic stimuli. Normal ageing hinders SC proliferation and differentiation, and is associated with increased expression of a number of pro-apoptotic factors in skeletal muscle. In light of previous studies that have demonstrated age-related altered expression of genes involved in SC antioxidant and repair activity, this investigation was aimed at evaluating the incidence of apoptotic features in human SCs. Primary cells were obtained from vastus lateralis of nine young (27.3±2.0 years old) and nine old (71.1±1.8 years old) subjects, and cultured in complete medium for analyses at 4, 24, 48, and 72 h. Apoptosis was assessed using AnnexinV/propidium iodide staining, the terminal deoxynucleotidyl transferase dUTP nick-end labelling technique, RT-PCR, DNA microarrays, flow cytometry, and immunofluorescence analysis. There was an increased rate of apoptotic cells in aged subjects at all of the experimental time points, with no direct correlation between AnnexinV-positive cells and caspase-8 activity. On the other hand, CASP2, CASP6, CASP7, and CASP9 and a number of cell death genes were upregulated in the aged SCs. Altogether, our data show age-related enhanced susceptibility of human SCs to apoptosis, which might be responsible for their reduced response to muscle damage.
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