Reduction in Reactive Oxygen Species Production by Mitochondria From Elderly Subjects With Normal and Impaired Glucose Tolerance
| Autor: | Muhammad A. Abdul-Ghani, Ralph A. DeFronzo, Holly Van Remmen, Nicolas Musi, Sangeeta Ghosh, Benjamin P. Bowen, Joaquin Joya-Galeana, Natalie Lefort, Lawrence J. Mandarino, Raweewan Lertwattanarak, Arlan Richardson, Marjorie Molina-Carrion, José de Jesús Garduño-García |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Proteomics Mitochondrial ROS Aging medicine.medical_specialty Adolescent endocrine system diseases Endocrinology Diabetes and Metabolism Type 2 diabetes Biology Mitochondrion Mitochondrial Proteins Impaired glucose tolerance 03 medical and health sciences Adenosine Triphosphate 0302 clinical medicine Internal medicine Glucose Intolerance Internal Medicine medicine Humans Aerobic exercise NRF1 Exercise Heat-Shock Proteins Aged 030304 developmental biology chemistry.chemical_classification 0303 health sciences Reactive oxygen species ATP synthase Nuclear Respiratory Factor 1 Gene Expression Profiling nutritional and metabolic diseases medicine.disease Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Mitochondria DNA-Binding Proteins Metabolism Endocrinology chemistry biology.protein Lipid Peroxidation Reactive Oxygen Species hormones hormone substitutes and hormone antagonists 030217 neurology & neurosurgery Transcription Factors |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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