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J Clin Immunol (2009) 29:416425 DOI 10.1007/s10875-009-9298-4
NK and NKT Cells in Aging and Longevity: Role of Zinc and Metallothioneins
Eugenio Mocchegiani & Robertina Giacconi &
Catia Cipriano & Marco Malavolta
Received: 18 April 2009 /Accepted: 20 April 2009 /Published online: 1 May 2009 # Springer Science + Business Media, LLC 2009
AbstractIntroduction 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. Discussion 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- (IFN-) production by both activated types of cells. Both NK and NKT cell cytotoxicity and IFN- production increase in very old age with respect to normal aging, especially by NKT cells bearing TCR. 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.
Keywords NK cell . NKT cells . Cytotoxicity. Cytokine production . Innate immunity. Adaptive immunity. Zinc . Metallothioneins . Aging . Longevity
Introduction
The progressive lengthening of the mean life span and the consequent growth of the elderly population during the last decades has focused the attention of the scientific community on the role played by some body homeostatic mechanisms in aging and in human longevity. Aging is a complex process characterized by a general decline in physiological functions with increased morbidity and mortality. The specific causes are not known or not well defined. Several studies suggest an association among changes in immune functions, aging, and longevity, and indicate that the deterioration of the immune functions, termed immunosenescence, could be the cause to the increased susceptibility to infection and cancer in old organisms, including humans [1].
However, dysregulation in the immune functions are normally counterbalanced by a continuous adaptation of...