The validity of the oxidative stress hypothesis of aging has sometimes been questioned because the administration of low molecular weight antioxidants such as α-tocopherol does not retard the aging process and extend maximum life span. Thus, the goal of the current study was to determine if increased oral intake of α-tocopheryl acetate indeed results in its augmentation in tissues or in their mitochondria, and whether or not this causes an attenuation of oxidative damage. Groups of relatively old (21 months) experimental mice were fed a diet supplemented with 1.65 g/kg α-tocopheryl acetate or the base diet (NIH-31), for 13 weeks. Supplementation with α-tocopheryl acetate increased α-tocopherol concentrations ∼3-5-fold in plasma and in tissue homogenates and ∼2-3-fold in mitochondria from liver, skeletal muscle and heart of the mice. However, supplementation affected neither the rate of heart mitochondrial H2O2 generation nor products of lipid peroxidation (thiobarbituric acid-reactive substances) and protein oxidation (protein carbonyls). Thus, in contrast to life-extending interventions such as caloric restriction, that can produce relatively rapid decreases in oxidative damage, supplementation with α-tocopheryl acetate had little or no impact on the steady-state level of cellular oxidative damage. This difference could explain why α-tocopherol administration has been found to be ineffective in the extension of the life span.
- Oxidative damage
- Oxidative stress