Age-related changes in the mitotic and metabolic characteristics of muscle-derived cells
Age-related changes in the mitotic and metabolic characteristics of muscle-derived cells
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DOI：
10.1152/japplphysiol.00437.2003
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发表时间：
2003-11-01
影响因子：
3.3
通讯作者：
Freyssenet, D
中科院分区：
文献类型：
--
作者：
Barani, AE;Durieux, AC;Freyssenet, D
与年龄相关的肌肉减少症可能部分是由于不完全修复和再生的累积反复发作。我们假设与卫星细胞激活和增殖相关的有丝分裂和代谢事件可能随着年龄的增长而改变。从幼年（3周龄）、成年（9月龄）和老年（24月龄）sd - dawley雄性大鼠腓肠肌和股四头肌中分离肌肉源性细胞（mdc） （n = 10/组）。与成年和老年动物相比，幼龄大鼠的mdc开始增殖得更早。随着年龄的增长，细胞周期持续时间从36.5 +/- 3.2 h显著缩短至28.0 +/- 2.2 h。而非循环（G(0)期）和循环(G（1) + S + G(2) + M期）培养的mdc比例在三个年龄组中均无统计学变化。血清刺激后，老龄大鼠培养mdc中c-met和增殖细胞核抗原表达的增加明显降低。血清刺激后观察到柠檬酸合成酶、乳酸脱氢酶、蛋白酶体、caspase 3、纤溶酶原激活剂（PAs）和基质金属蛋白酶2 - 9 （MMP2 - 9）的表达发生了重大变化，但没有发现与年龄相关的差异。然而，当测定粉碎肌肉提取物时，PAs和MMP2 - 9酶活性随着年龄的增长而显著降低。我们的研究结果表明，与mdc激活和增殖控制相关的细胞和生化事件随着年龄的增长而发生。这些改变可能参与了整个生命周期中不完全修复和再生的反复发作的积累，从而导致骨骼肌质量和功能随着年龄的增长而丧失。
Age-related sarcopenia could partly result from cumulative repeated episodes of incomplete repair and regeneration. We hypothesized that mitotic and metabolic events associated with satellite cell activation and proliferation could be altered with aging. Muscle-derived cells (mdc) were isolated from gastrocnemius and quadriceps muscles of young (3 wk old), adult (9 mo old), and old (24 mo old) Sprague-Dawley male rats (n = 10/group). The mdc from young growing rats started to proliferate earlier compared with adult and old animals. Cell cycle duration was significantly reduced with aging from 36.5 +/- 3.2 to 28.0 +/- 2.2 h. However, the proportion of noncycling (G(0) phase) and cycling (G(1) + S + G(2) + M phases) cultured mdc was statistically unchanged among the three age groups. Significantly lower increase in c-met and proliferating cell nuclear antigen expression were observed in cultured mdc of old rats upon serum stimulation. Major changes in the expression of citrate synthase, lactate dehydrogenase, proteasome, caspase 3, plasminogen activators (PAs), and matrix metalloproteinase 2 - 9 (MMP2 - 9) were observed upon serum stimulation, but no age-related difference was noted. However, when measured on crushed muscle extracts, PAs and MMP2 - 9 enzyme activities were significantly decreased with aging. Our results show that cellular and biochemical events associated with the control of mdc activation and proliferation occur with aging. These alterations may participate in the accumulation of repeated episodes of incomplete repair and regeneration throughout the life span, thus contributing to the loss of skeletal muscle mass and function with aging.