Zinc-binding proteins (metallothionein and α-2 macroglobulin) as potential biological markers of immunosenescence

Zinc is the most relevant trace element for the maintenance of numerous homeostatic mechanisms in the body. In particular, zinc plays a pivotal role in the function of the entire immune system for the entire life of an organism. The binding of zinc with some proteins, such as metallothioneins [MT] and α-2 macroglobulin [α-2M] is crucial immune efficiency during ageing and also in age-related diseases [cancer and infection]. These proteins may turn from a role of protection against cellular oxidative damage in young-adult age to a harmful role in ageing. Indeed, these proteins increase abnormally during ageing and according to their original biological function, they continuously sequester intracellular zinc. This provokes abnormally low zinc ion bio-availability for the immune system either at thymic or extrathymic level. The latter is prominent in ageing. As a result, an impaired immune function occurs in ageing. Physiological zinc supplementation restores the immune system, which leads to an increased rate of survival in old mice. Zinc supplementation does not interfere with the high levels of MT or α-2M. Therefore, zinc supplementation is of benefit in ageing and in age-related diseases [cancer and infection]. Moreover, zinc-binding proteins regain their original role of cellular protection against oxidative damage after zinc supplementation.