Roles of Nutritional Selenium in Mouse Aging and Age‐related Degenerations

Abstract

A role of selenium (Se), particularly, at nutritional levels of intake, in aging is not fully understood. In particular, what is lacking is an appropriate aging model of dietary Se deprivation relative to human physiology displaying features of normal aging and age-related degenerations. Telomere attrition provokes DNA damage response and, subsequently, replicative senescence. Because the chromosomes of mice carry longer telomeres than those of humans, we propose that lengthy telomeres preclude mice deprived of Se to display aging phenotypes and age-related disorders. To test this hypothesis, weanling late generation Terc-/- mice were fed a Se-deficient diet or the diet supplemented with selenate (0.15 ppm) throughout their life. As evidenced by changes in metabolic markers (body weight, glucose intolerance, insulin resistance and bone structure) and aging phenotypes (grey hair, alopecia and wound healing), our data strongly indicate health span deterioration by dietary Se deficiency in the short telomere mice. MicroRNAs (miRNA) have been proposed as biomarkers for a variety of diseases and physiological conditions, including aging. To identify the key circulatory mediators during the aging process, we used a high-throughput platform, TaqMan low density array to profile more than 800 miRNAs in plasma, and validated the expression of miRNAs using individual quantitative PCR. Altogether, we have thus established a very interesting model of aging by deprivation of Se that displays many hallmarks of human aging and can reveal the roles of Se at nutritional levels, in contrast with previous approaches in which this effect may have been masked by lengthy telomeres.