|ZHANG, LI - Mississippi State University|
|CHENG, WEN-HSING - Mississippi State University|
Submitted to: Free Radical Biology and Medicine
Publication Type: Review Article
Publication Acceptance Date: 5/17/2018
Publication Date: 5/22/2018
Citation: Zhang, L., Zeng, H., Cheng, W. 2018. Beneficial and paradoxical roles of selenium at nutritional levels of intake in healthspan and longevity. Free Radical Biology and Medicine. https://doi.org/10.1016/j.freeradbiomed.2018.05.067.
Interpretive Summary: Aging is a process with progressive declines in physiological functions due to damage accumulation at the molecular and tissue levels due to endogenous and exogenous factors throughout life. Selenium (Se) is an essential trace element for humans and animals and regulates the functions of many cellular proteins by being a chemical component of selenoproteins. The protective roles of many selenoproteins in optimal health are well documented. However, certain selenoproteins are reported to paradoxically exert adverse physiological consequences based on cellular and mouse models. Thus, elucidating the impact of selenium on healthspan and longevity is important for disease prevention. This article reviews the status of knowledge concerning selenoproteins in this research area. The information will be useful for scientists and health-care professionals who are interested in Se nutrition and disease prevention.
Technical Abstract: Accumulation of damage to the genome and macromolecules is a hallmark of aging, age-associated degeneration, and genome instability syndromes. Although the processes of aging are irreversible, they can be modulated by genome maintenance pathways and environmental factors such as diet. Selenium (Se) at nutritional levels of intake confers its physiological functions mainly through selenoproteins, but Se compounds and Se non-specifically incorporated into proteins also impact health at deficient and supranutritional or toxic levels. Bruce Ames proposed the contribution of a subset of low hierarchy selenoproteins to the aging process. In this regard, selenotranscriptomic analyses from two independent studies collectively suggest the parallel downregulation of a small number of selenoproteins by Se deficiency and age or senescence. Results from gene knockout or knockdown experiments in mice and cells in general show early onset of age-associated symptoms and defective redox and genome maintenance, but paradoxical roles of selenoproteins that would otherwise deteriorate health are also observed under distinct conditions. While healthspan and longevity are generally thought to be projected in parallel, here we present evidence and plausible mechanisms in an attempt to understand a possible trade-off between longevity promotion and healthspan deterioration together with damage accumulation. We propose that longevity promotion in Se deficiency is attributed to reduced expression of health-deteriorating selenoproteins such as TXNRD1during carcinogenesis, and stress-response hormesis in non-selenoprotein forms. A couple of selenoproteins, including SELENOH, are postulated to confer Se functions in redox and genome maintenance and senescence. This review highlights the need to pinpoint specific roles of selenoproteins and Se compounds for healthy aging in healthspan and lifespan that differ by body Se status, disease, and life cycle.