Oxidative stress and the mitochondrial theory of aging in human skeletal muscle
Oxidative stress and the mitochondrial theory of aging in human skeletal muscle
复制标题
DOI：
10.1016/j.exger.2004.06.002
复制
发表时间：
2004-09-01
影响因子：
3.9
通讯作者：
Tarnopolsky, MA
中科院分区：
文献类型：
--
作者：
Gianni, P;Kaczor, JJ;Tarnopolsky, MA
根据衰老的线粒体理论，与年龄相关的氧化应激增加是细胞损伤和最终细胞死亡的原因。尽管有令人信服的证据支持某些组织的线粒体衰老理论，但有关骨骼肌衰老的数据并不一致。我们收集了年轻（N = 12，类似于22岁）和老年（N = 12，类似于72岁）男性的股外侧肌静息肌活检和24小时尿液样本。老年男性尿8-OHdG显著高于年轻男性（老年：7714 1402，年轻：5333 +/- 1191 ng g（-1）肌酐：p = 0.005）。蛋白质羰基水平也是如此（老年人：0.72 +/- 0.42，年轻人：0.26 +/- 0.14 nmol mg（-1）蛋白质：p = 0.007）。MnSOD活性（老年人：7.1 +/- 0.8，年轻人：5.2 +/- 1.8 U mg（-1）蛋白质：p = 0.04）和过氧化氢酶活性（老年人：8.5 +/- 2.0。年轻人：6.2 +/- 2.4 mumol min（-1）mg（-1）protein：p = 0.02）在老年人中分别显著高于年轻人，而总SOD或CuZnSOD没有观察到差异。与年轻男性相比，老年男性的全长mtDNA出现较低，并且在6/8的老年男性和0/6的年轻男性中存在mtDNA缺失（p = 0.003）。柠檬酸合酶和复合物II + III和IV的最大活性在年轻人和老年人之间没有差异，然而，与年轻人相比，老年人中复合物I + III活性略高（老年人：2.5 +/-0.5。年轻：1.9 +/- 0.5 mumol min（-1）g（-1）w.w：p = 0.03）。总之，健康的老龄化与蛋白质和DNA的氧化损伤，抗氧化酶的补偿性上调和mtDNA的畸变有关，电子传递链最大酶活性没有降低。(C)2004年爱思唯尔公司All rights reserved.
According to the mitochondrial theory of aging, an age-related increase in oxidative stress is responsible for cellular damage and ultimately cell death. Despite compelling evidence that supports the mitochondrial theory of aging in some tissues, data regarding aging skeletal muscle are inconsistent. We collected resting muscle biopsies from the vastus lateralis, and 24 h urine samples from, young (N = 12, similar to22 yr), and older (N = 12, similar to72 yr) men. Urinary 8-OHdG was significantly higher in older as compared to younger men (Old: 7714 1402, Young: 5333 +/- 1191 ng g(-1) creatinine: p = 0.005). as were levels of protein carbonyls (Old: 0.72 +/- 0.42, Young: 0.26 +/- 0.14 nmol mg(-1) protein: p = 0.007). MnSOD activity (Old: 7.1 +/- 0.8, Young: 5.2 +/- 1.8 U mg(-1) protein: p = 0.04) and catalase activity (Old: 8.5 +/- 2.0. Young: 6.2 +/- 2.4 mumol min(-1) mg(-1) protein: p = 0.02) were significantly higher in old as compared to young men, respectively, with no differences observed for total or CuZnSOD. Full-length mtDNA appeared lower in old as compared to young men, and mtDNA deletions were present in 6/8 old and 0/6 young men (p = 0.003). The maximal activities of citrate synthase, and complex II + III, and IV were not different between young and old men, however, complex I + III activity was marginally higher in older as compared to younger men (Old: 2.5 +/- 0.5. Young: 1.9 +/- 0.5 mumol min(-1) g(-1) w.w: p = 0.03) respectively. In conclusion, healthy aging is associated with oxidative damage to proteins and DNA, a compensatory up-regulation of antioxidant enzymes, and aberrations of mtDNA, with no reduction in electron transport chain maximal enzyme activity. (C) 2004 Elsevier Inc. All rights reserved.