The immune system and the impact of zinc during aging

Abstract

The trace element zinc is essential for the immune system, and zinc deficiency affects multiple aspects of innate and adaptive immunity. There are remarkable parallels in the immunological changes during aging and zinc deficiency, including a reduction in the activity of the thymus and thymic hormones, a shift of the T helper cell balance toward T helper type 2 cells, decreased response to vaccination, and impaired functions of innate immune cells. Many studies confirm a decline of zinc levels with age. Most of these studies do not classify the majority of elderly as zinc deficient, but even marginal zinc deprivation can affect immune function. Consequently, oral zinc supplementation demonstrates the potential to improve immunity and efficiently downregulates chronic inflammatory responses in the elderly. These data indicate that a wide prevalence of marginal zinc deficiency in elderly people may contribute to immunosenescence.

Figure 1

Zinc as a signal molecule for immune cells. Zinc homeostasis is tightly controlled by three mechanisms: (A) Transport through the plasma membrane by zinc transporters from the ZnT (SLC A30) or ZIP (SLC A39) families. (B) Buffering by metallothionein. (C) Reversible transport by ZnT and ZIP proteins into or out of zincosomes, and storage bound to ligands that form a zinc sink. Zinc signals, i.e., changes in the intracellular concentration of free zinc, control immune cell signal transduction by regulating the activity of major signaling molecules, including kinases, phosphatases, and transcription factors. One representative example for each group is given. (TCR, T cell receptor; MKP, MAPK phosphatase; MTF-1, metal-response element binding transcription factor-1).

Figure 2

Disturbed B-cell function in ageing. In general, the numbers of B cells and specific antibodies (e.g., in response to vaccination) decrease with age, while total and unspecific immunoglobulin and autoantibodies increase. Some B cell clones expand, resulting in higher probability for lymphocyte malignancies.

Figure 3

Influence of zinc on age-related changes of immune function. Aging leads to an increase in pro-inflammatory cytokines and modulates the TH1–TH2 balance toward a TH2 response by reducing the TH-1 cytokines IFN-α and -γ and increasing IL-10. This reduces T cell help for immunoglobulin class switch and causes unspecific activation of B cells. Zinc counteracts the effects on [a] pro-inflammatory cytokines [27], [b] IFN-α [73], [c] IFN-γ [92], and [d] IL-10 [93].