Beccafico S, Puglielli C, Pietrangelo T, Bellomo R, Fanò G, Fulle S
Department of Basic and Applied Medical Sciences, University "G. d'Annunzio" Nuovo Polo Didattico Pal. B, Via dei Vestini 29, Chieti I-66013, Italy.
Ann N Y Acad Sci. 2007 Apr;1100:345-52. doi: 10.1196/annals.1395.037.
In humans aging is a complex process that determines many physical and metabolic alterations correlated to the accumulation of oxidative damage in different tissues. Sarcopenia is an age-related nonpathological condition that includes a progressive loss of mass and strength in skeletal muscle, associated with a decline in the fibers' functional capability. This condition could be correlated to abnormal reactive oxygen species (ROS) accumulation with consequent fiber oxidative damage. This complex situation is not only evident in mature muscle fibers but also in muscle resident satellite cells (involved in fiber damage repairing) in which some functional parameters, at least for that concerns the Ca(2+) homeostasis, seem to be modified. In fact, our data show that there is an age-dependent increase of lipid peroxidation, in cultured myotubes (differentiated and fused satellite cells) after 7 days of in vitro differentiation. In these substrates also the capacity of these cells to produce Ca(2+) transient in response to various stimuli (ATP, caffeine, nicotine, KCl) is, sometimes, drastically modified. In particular, the presence of an age-dependent defective status of excitation-contraction (EC) coupling apparatus is supported by a single cell Ca(2+) analysis obtained from myotubes (derived from aged muscles) in the presence of 40 mM caffeine or 40 mM KCl. The alkaloid presence induces a complete emptying of ryanodine-dependent calcium stores indicating a probable integrity both of SR-terminal cisternae and/or the specific Ca(2+) channel known as RyR1. However, if a sarcolemmal depolarization is induced by the addition of 40 mM KCl in the experimental medium then Ca(2+) release RyR1-dependent can be observed only if Ca(2+) is present in the experimental solution. These results suggest that the EC uncoupling status could be due to the alteration of the interaction between RyR and DHPR. The two receptors are present and functionally active in myotubes from aged donors but they are probably still not in the right localization. These results suggest that during donor's life the satellite cells undergo an aging process similar to the one observed in skeletal muscle tissue, even if they are in a quiescence status for most of the time.
在人类中，衰老过程十分复杂，它会引发许多与不同组织中氧化损伤积累相关的生理和代谢变化。肌肉减少症是一种与年龄相关的非病理性状况，包括骨骼肌质量和力量的逐渐丧失，并伴有肌纤维功能能力的下降。这种状况可能与活性氧（ROS）的异常积累以及随之而来的纤维氧化损伤有关。这种复杂情况不仅在成熟肌纤维中明显，在肌肉驻留卫星细胞（参与纤维损伤修复）中也很明显，其中一些功能参数，至少就钙（Ca2+）稳态而言，似乎发生了改变。事实上，我们的数据表明，在体外分化7天后的培养肌管（分化并融合的卫星细胞）中，脂质过氧化存在年龄依赖性增加。在这些细胞中，它们对各种刺激（ATP、咖啡因、尼古丁、氯化钾）产生Ca2+瞬变的能力有时也会发生显著改变。特别是，从存在40 mM咖啡因或40 mM氯化钾的情况下从肌管（源自老年肌肉）获得的单细胞Ca2+分析支持了存在年龄依赖性的兴奋 - 收缩（EC）偶联装置缺陷状态。生物碱的存在会导致依赖兰尼碱的钙储存完全排空，这表明肌浆网终末池和/或称为RyR1的特定Ca2+通道可能是完整的。然而，如果在实验培养基中添加40 mM氯化钾诱导肌膜去极化，那么只有当实验溶液中存在Ca2+时，才能观察到依赖RyR1的Ca2+释放。这些结果表明，EC解偶联状态可能是由于RyR和二氢吡啶受体（DHPR）之间相互作用的改变所致。这两种受体在老年供体的肌管中存在且功能活跃，但它们可能仍未处于正确的定位。这些结果表明，在供体生命过程中，卫星细胞经历了类似于在骨骼肌组织中观察到的衰老过程，即使它们大部分时间处于静止状态。
