Reduction in reactive oxygen species production by mitochondria from elderly subjects with normal and impaired glucose tolerance.
Reduction in reactive oxygen species production by mitochondria from elderly subjects with normal and impaired glucose tolerance.
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作者：
Ghosh S;Lertwattanarak R;Lefort N;Molina-Carrion M;Joya-Galeana J;Bowen BP;Garduno-Garcia Jde J;Abdul-Ghani M;Richardson A;DeFronzo RA;Mandarino L;Van Remmen H;Musi N
衰老增加了发生糖耐量受损（IGT）和2型糖尿病的风险。有人提出，功能失调的线粒体产生的活性氧（ROS）增加可能在这些代谢异常的发病机制中起作用。我们研究了衰老本身（在糖耐量正常[NGT]的受试者中）是否会损害线粒体功能及其与ROS生成的关系，IGT的老年受试者是否会进一步恶化线粒体功能（ATP生成降低和ROS生成升高），以及运动是否会逆转与年龄相关的线粒体功能变化。在年轻NGT患者、老年NGT患者和老年IGT患者的肌肉中测量线粒体ATP和ROS的产生。在有氧运动16周之前和之后进行测量。老年NGT患者和老年IGT患者与年轻患者相比，ATP合成较低。值得注意的是，与年轻组相比，年龄较大的受试者（具有NGT和IGT）的线粒体显示出ROS生成减少。老年组之间ATP和ROS的产生相似。运动增加了三组的ATP合成。线粒体ROS的产生也在训练后增加。蛋白质组学分析显示，随着年龄的增长，几种电子传递链蛋白的下调，而运动可以逆转这种情况。来自NGT和IGT受试者的旧线粒体显示线粒体功能障碍，表现为ATP产生减少，但不涉及ROS产生增加。当调整到年龄时，老年人IGT的发展不涉及线粒体ATP和ROS产生的变化。最后，运动可以逆转旧线粒体的线粒体表型（蛋白质组和功能）。
Aging increases the risk of developing impaired glucose tolerance (IGT) and type 2 diabetes. It has been proposed that increased reactive oxygen species (ROS) generation by dysfunctional mitochondria could play a role in the pathogenesis of these metabolic abnormalities. We examined whether aging per se (in subjects with normal glucose tolerance [NGT]) impairs mitochondrial function and how this relates to ROS generation, whether older subjects with IGT have a further worsening of mitochondrial function (lower ATP production and elevated ROS generation), and whether exercise reverses age-related changes in mitochondrial function. Mitochondrial ATP and ROS production were measured in muscle from younger individuals with NGT, older individuals with NGT, and older individuals with IGT. Measurements were performed before and after 16 weeks of aerobic exercise. ATP synthesis was lower in older subjects with NGT and older subjects with IGT versus younger subjects. Notably, mitochondria from older subjects (with NGT and IGT) displayed reduced ROS production versus the younger group. ATP and ROS production were similar between older groups. Exercise increased ATP synthesis in the three groups. Mitochondrial ROS production also increased after training. Proteomic analysis revealed downregulation of several electron transport chain proteins with aging, and this was reversed by exercise. Old mitochondria from subjects with NGT and IGT display mitochondrial dysfunction as manifested by reduced ATP production but not with respect to increased ROS production. When adjusted to age, the development of IGT in elderly individuals does not involve changes in mitochondrial ATP and ROS production. Lastly, exercise reverses the mitochondrial phenotype (proteome and function) of old mitochondria.