Role of Zinc and Selenium in Oxidative Stress and Immunosenescence: Implications for Healthy Aging and Longevity

Aging is a complex process that includes gradual and spontaneous biochemical and physiological changes which contributes to a decline in performance and increased susceptibility to diseases. Zn and Se are essential trace elements that play a pivotal role in immune functions and antioxidant defense and, consequently, are claimed to play also a role in successful aging trajectories. Consistently with their nature of essential trace elements, a plethora of data obtained “in vitro” and “in vivo” (in humans and animal models) support the relevance of Zn and Se for both the innate and adoptive immune response. Moreover, Zn and Se are strictly involved in the synthesis and regulation of activity of proteins and enzymes, e.g., metallothioneins (MT) and glutathione peroxidase (GPX), that are necessary for our endogenous antioxidant response. This is clearly important to protect our cells from oxidative damage and to slow the decline of our immune system with aging. Age-related changes affecting tissue levels of Zn and Se may indicate that the risk of Zn and Se deficiency increases with aging. However, it is still unclear which of these changes can be the consequence of a “real deficiency” and which can be part of our physiological compensatory response to the accumulating damage occurring in aging. Furthermore, the upregulation of antioxidant proteins (Zn and Se dependent) may be a manifestation of self-induced oxidative stress. By the way, Zn and Se dependent proteins are modulated not only by nutritional status, but also by well-known hallmarks of aging that play antagonistic functions, such as the deregulated nutrient sensing pathways and cellular senescence. Thus, it is not an easy task to conduct Zn or Se supplementation in elderly and it is emerging consistent that these kind of supplementation requires an individualized approach. Anyway, there is consistent support that supplementation with Zn using doses around 10 mg/day is generally safe in elderly and may even improve part of immune performances in those subjects with a baseline deficiency. Regarding Se supplementation, it may induce both beneficial and detrimental effects on cellular immunity depending on the form of Se, supplemental dose, and delivery matrix. The nutritional association of supplements based on “Zn plus Se” is hypothesized to provide additional benefits, but this will likely need a more complex individualized approach. The improvement of our knowledge around screening and detection of Zn and Se deficiency in aging could lead to substantial benefits in terms of efficacy of nutritional supplements aimed at ameliorate performance and health in aging.