During aging, dysregulated immune functions occur contributing to increased susceptibility to morbidity and mortality. However, these dysregulations are normally counterbalanced by continuous adaptation of the body to the deteriorative changes occurring over time. These adaptive changes well occur in healthy centenarians.
Both innate (natural) and adaptive (acquired) immune responses decline with advancing age. Natural killer (NK) and natural killer T (NKT) cell cytotoxicity, representing one of best models of innate immune response, decreases in aging as well as interferon-gamma (IFN-gamma) production by both activated types of cells. Both NK and NKT cell cytotoxicity and IFN-gamma production increase in very old age with respect to normal aging, especially by NKT cells bearing TCRgammadelta. The role played by zinc and metallothioneins (MT) is crucial because this affects NK and NKT cell development, maturation, and functions. In particular, some MT polymorphisms are involved in maintaining innate immune response and intracellular zinc ion availability in aging with thus a role of MT genetic background to escape some age-related diseases with subsequent healthy aging and longevity.