Selenium in Aging and Longevity

Selenium is an essential dietary micronutrient, exerting beneficial effects over a limited range of concentrations. Insufficient dietary intake of selenium increases the risk of type 2 diabetes, infertility, immune dysfunction, prostate cancer, cognitive decline, prostate cancer, colorectal cancer in females, skeletal muscle disorders, overall mortality and an endemic cardiomyopathy known as Keshan disease. Excessive intake of selenium is toxic, leading to a condition termed selenosis, that is associated with damage to the nails, dermatitis, alopecia, central nervous system dysfunction and death. Selenium exerts its biological effects through low-molecular weight molecules, through a small family of selenoproteins which contain the 21^st amino acid selenocysteine, and via selenium-binding proteins, in which an atom of selenium is covalently bound to a cysteine residue. In addition to being regulated by body selenium status, the abundance and function of these biomolecules can be controlled by other dietary components (including copper, zinc, folic acid, resveratrol, vitamin A and α-linoleic acid) and other factors, such as exercise and caloric restriction. This review comprehensively surveys the effects of selenium-containing biomolecules on aging and aims to generate rationales underpinning the biphasic effects of this element on life-span, health-span and disease. This will provide a framework for understanding the effects of selenium on mechanisms of aging, as the starting point for development of interventions that will promote longevity and health-span.