Supplementation with vitamin E fails to attenuate oxidative damage in aged mice.
The validity of the oxidative stress hypothesis of aging has sometimes been questioned because the administration of low molecular weight antioxidants such as alpha-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 alpha-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 alpha-tocopheryl acetate or the base diet (NIH-31), for 13 weeks. Supplementation with alpha-tocopheryl acetate increased alpha-tocopherol concentrations approximately 3-5-fold in plasma and in tissue homogenates and approximately 2-3-fold in mitochondria from liver, skeletal muscle and heart of the mice. However, supplementation affected neither the rate of heart mitochondrial H(2)O(2) 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 alpha-tocopheryl acetate had little or no impact on the steady-state level of cellular oxidative damage. This difference could explain why alpha-tocopherol administration has been found to be ineffective in the extension of the life span.
Sumien
Nathalie
N
Department of Pharmacology and Neuroscience, Institute for Aging and Alzheimer's Disease Research, University of North Texas Health Science Center at Fort Worth, 3500 Camp Bowie Blvd, Fort Worth, TX 76107-2699, USA.
Forster
Michael J
MJ
Sohal
Rajindar S
RS
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000493:pharmacokinetics / Q000494:pharmacology*; D019587:Dietary Supplements; D006861:Hydrogen Peroxide / Q000378:metabolism; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011506:Proteins / Q000378:metabolism; D014018:Tissue Distribution; D024505:Tocopherols; D024502:alpha-Tocopherol / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology*
D000975:Antioxidants; D011506:Proteins; D006861:Hydrogen Peroxide; D024502:alpha-Tocopherol; D024505:Tocopherols