Analyses of selenotranscriptomes and selenium concentrations in response to dietary selenium deficiency and age reveal common and distinct patterns by tissue and sex in telomere-dysfunctional mice

Authors: CAO, LEI - Mississippi State University; Zeng, Huawei; WU, RYAN - University Of Maryland; WU, TUNG-LUNG - Mississippi State University; CHENG, WEN-HSING - Mississippi State University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/7/2017
Publication Date: 10/1/2017
Publication URL: http://handle.nal.usda.gov/10113/6472286
Citation: Cao, L., Zeng, H., Wu, R.T., Wu, T., Cheng, W. 2017. Analyses of selenotranscriptomes and selenium concentrations in response to dietary selenium deficiency and age reveal common and distinct patterns by tissue and sex in telomere-dysfunctional mice. Journal of Nutrition. 147(10):1858-1866.

Interpretive Summary: Selenium (Se), an essential nutrient for humans and animals, is involved in a diverse range of chronic diseases primarily through selenoproteins and Se metabolites. However, Se’s nutritional and physiological roles in different sexes during the aging process remain elusive. We have recently shown that long-term dietary Se deprivation accelerates aging signs such as grey hair, cataract, delayed wound healing, osteoporosis. To determine the effects of long-term dietary Se deprivation, aging, and sex on selenoprotein gene expression, we examined the tissues of aged male and female mice. Our results demonstrate that selenoprotein expression was greatly differed by aging, sex, and tissue type in the context of dietary Se deprivation. Furthermore, we identified a set of selenoprotein genes (e.g., Selenoh) that may serve as potential marker genes responsible for the effect of dietary Se deprivation on aging. The information will be useful for scientists and health-care professionals who are interested in using selenium as a nutrient and human aging issue.

Technical Abstract: Background: While sex and aging are known to impact mRNA abundance of several selenoproteins, this has not been examined comprehensively or in aged mice. By employing telomerase RNA component knockout (Terc-/-) mice carrying humanized telomeres, long-term dietary selenium (Se) deprivation has recently been shown to oppositely impact longevity and healthspan. Objective: Determine the effects of sex, aging, and long-term dietary Se deprivation on selenotranscriptomes in tissues of aged Terc-/- mice. Methods: Weanling male and female Terc-/- mice were fed an AIN-93G, Torula yeast basal diet or the diet supplemented with 0.15 mg Se/kg (as sodium selenate) until 18- or 24-months old. Selenotranscriptomes in heart, kidney, liver, and testis and body Se status were analyzed. Results: Four unique patterns were generalized: 1) selenotranscriptomes responded to aging and dietary Se deprivation in a sex- and tissue-specific manner; 2) a few selenoproteins responded in parallel to dietary Se deprivation and aging and Selenoh appeared to be the most prominent one; 3) while the majority of selenoprotein mRNAs was down-regulated, some were up-regulated by aging or dietary Se deprivation in kidney; and 4) 9 selenoprotein mRNAs in testis were up-regulated by aging in Se-deficient mice. In particular, while aging reduced the expression of 13 selenoprotein mRNAs in liver of males but none in females, the opposite trend was true in heart. Plasma and liver Se concentrations differed by sex at 18-months and by aging in Se-adequate males. Conclusions: Sex, aging, and dietary Se deprivation differentially impacted selenotranscriptomes in tissues of aged Terc-/- mice. A subset of selenoprotein mRNAs is commonly down-regulated by aging and dietary Se deprivation in a tissue, suggesting candidate selenoproteins responsible for the effect of dietary Se deprivation on age-related physiological changes.