Rebalancing the unbalanced aged immune system – A special focus on zinc

Nowadays, aging is understood as a dynamic and multifaceted dysregulation process that spares almost no human organ or cell. The immune system being among the most affected, it has been shown predominantly that its integrity determines the tightrope walk between the difference of escaping or suffering from age-related diseases. Next to drug-based anti-aging strategies, micronutrient intervention may represent an emerging but less radical way to slow immune aging. While a sufficient supply of a variety of micronutrients is undeniably important, adequate intake of the trace element zinc appears to tower over others in terms of reaching old age. Inconveniently, zinc deficiency prevalence among the elderly is high, which in turn contributes to increased susceptibility to infection, decreased anti-tumor immunity as well as attenuated response to vaccination. Driven by this research, this review aims to provide a comprehensive and up-to-date overview of the various rebalancing capabilities of zinc in the unbalanced immune system of the elderly. This includes an in-depth and cell type-centered discussion on the role of zinc in immunosenescence and inflammaging. We further address upcoming translational aspects e.g. how zinc deficiency promotes the flourishing of certain pathogenic taxa of the gut microbiome and how zinc supply counteracts such alterations in a manner that may contribute to longevity. In the light of the ongoing COVID-19 pandemic, we also briefly review current knowledge on the interdependency between age, zinc status, and respiratory infections. Based on two concrete examples and considering the latest findings in the field we conclude our remarks by outlining tremendous parallels between suboptimal zinc status and accelerated aging on the one hand and an optimized zinc status and successful aging on the other hand.