Do Antioxidants Extend Longevity in Invertebrate and Vertebrate Animals?

In the 1950’s Denham Harman proposed the Free Radical Theory of Aging whereby species lifespan and individual longevities are the consequence of free radical driven damage to biomolecules. This led to decades of research to ascertain the effect of altered antioxidant defense systems on aging and mortality in an array of species using reverse genetics and dietary manipulation. Within invertebrates, the data generally support the Free Radical Theory in that overexpression of antioxidant enzymes or dietary supplementation with antioxidant compounds increases longevity and resistance to oxidative damage. Likewise, genetic knockdown of antioxidant defenses generally shortens longevity within invertebrates. On the other hand, for endothermic vertebrates (i.e., birds and mammals) the results have been equivocal. Downregulation of antioxidant enzymes typically results in an increased oxidative burden, but without an appreciable effect on longevity, while dietary supplementation with antioxidants has little-to-no effect, at least at the concentrations used. Upregulation of antioxidant enzyme genes also fails to increase longevity in vertebrates most of the time. Interestingly, manipulating antioxidant defenses in fishes increases longevity in conjunction with reduced oxidative damage akin to what is seen in invertebrates. Since invertebrates and fishes are both exothermic this raises the possibility that the evolution of endothermy interferes with the ability of antioxidants to slow the aging process.