Highly resistant macromolecular components and low rate of generation of endogenous damage: two key traits of longevity.

Key characteristics relating oxidative damage to aging and longevity are reviewed. Available information indicates that the specific composition of tissue macromolecules (proteins, lipids and mitochondrial DNA) in long-lived animal species gives them an intrinsically high resistance to modification that likely contributes to the superior longevity of these species. This is obtained in the case of lipids by decreasing fatty acid unsaturation, and in the proteins by lowering their methionine content. Long-lived animals also show low rates of reactive oxygen species (ROS) generation and oxidative damage at their mitochondria. On the other hand, dietary restriction decreases mitochondrial ROS production and oxidative damage to mitochondrial DNA and proteins. These changes are due to the decreased intake of dietary proteins (not of lipids or carbohydrates) of the dietary restricted animals. In turn, these effects of protein restriction seem to be specifically due to the lowered methionine intake of the protein and dietary restricted animals. It is emphasized that both a low rate of generation of endogenous damage and an intrinsically high resistance to modification of tissue macromolecules are key traits of animal longevity.