Reduction in Reactive Oxygen Species Production by Mitochondria From Elderly Subjects With Normal and Impaired Glucose Tolerance
Open Access
- 18 July 2011
- journal article
- Published by American Diabetes Association in Diabetes
- Vol. 60 (8), 2051-2060
- https://doi.org/10.2337/db11-0121
Abstract
OBJECTIVE: 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. RESEARCH DESIGN AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.Keywords
This publication has 51 references indexed in Scilit:
- Diagnosis and Classification of Diabetes MellitusDiabetes Care, 2010
- Conditional knockout of Mn-SOD targeted to type IIB skeletal muscle fibers increases oxidative stress and is sufficient to alter aerobic exercise capacityAmerican Journal of Physiology-Cell Physiology, 2009
- Proteomics Analysis of Human Skeletal Muscle Reveals Novel Abnormalities in Obesity and Type 2 DiabetesDiabetes, 2009
- Reactive Oxygen Species Enhance Insulin SensitivityCell Metabolism, 2009
- Overexpression of Mn Superoxide Dismutase Does Not Increase Life Span in MiceThe Journals of Gerontology: Series A, 2009
- Endurance Exercise as a Countermeasure for AgingDiabetes, 2008
- Role of reactive oxygen species in contraction‐mediated glucose transport in mouse skeletal muscleThe Journal of Physiology, 2006
- Reactive oxygen species have a causal role in multiple forms of insulin resistanceNature, 2006
- Mitochondrial damage by the “pro-oxidant” peroxisomal proliferator clofibrateFree Radical Biology & Medicine, 1999
- Age-Associated Alterations of the Mitochondrial GenomeFree Radical Biology & Medicine, 1997