Therapeutics against mitochondrial oxidative stress in animal models of aging

Ann N Y Acad Sci. 2002 Apr;959:330-40. doi: 10.1111/j.1749-6632.2002.tb02104.x.

Abstract

During the course of normal metabolism, reactive oxygen species (ROS) are produced from within the respiratory chain of the mitochondria. These ROS have the capacity to oxidize and damage a variety of cellular constituents including lipids, DNA, and proteins. We have taken a genetic and pharmacological approach in delineating the range of molecular targets that can be oxidatively damaged by mitochondrial ROS. Specifically, we use mice that are lacking the mitochondrial form of superoxide dismutase (sod 2(-/-) mice) to better understand the possible phenotypes that can arise from mitochondrial oxidative stress. sod 2(-/-) mice can be used to test the efficacy of antioxidants, and more generally the efficacy of antioxidants against mitochondrial oxidative stress. We have evaluated superoxide dismutase/catalase mimetics in this mammalian model of mitochondrial oxidative stress, and have shown a high degree of efficacy in protecting against ROS produced within the mitochondria. Similarly, we have employed the nematode Caenorhabditis elegans to test the hypothesis that effective antioxidant therapy can prolong the life span of an invertebrate.

Publication types

  • Review

MeSH terms

  • Aging / physiology*
  • Animals
  • Antioxidants / metabolism*
  • Antioxidants / pharmacology*
  • Brain / pathology
  • Catalase / metabolism
  • Free Radical Scavengers / metabolism
  • Free Radical Scavengers / pharmacology
  • Life Expectancy
  • Metalloporphyrins / metabolism
  • Metalloporphyrins / pharmacology
  • Mice
  • Mice, Knockout
  • Mitochondria / enzymology
  • Mitochondria / metabolism*
  • Models, Animal
  • Oxidative Stress*
  • Reactive Oxygen Species / metabolism*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism

Substances

  • Antioxidants
  • Free Radical Scavengers
  • Metalloporphyrins
  • Reactive Oxygen Species
  • manganese(III)-tetrakis(4-benzoic acid)porphyrin
  • Catalase
  • Superoxide Dismutase
  • superoxide dismutase 2