With aging physical changes occur to cells in the body which are adaptive to the normal physical deterioration which occurs over time. With aging, the deterioration of immunity, called immunosenescence, is balanced by mechanisms seen in centenarians that allow some people to live to very old age.
An example of an adjustment in immunosenescence is change in the activity natural killer (NK) and natural killer T (NKT) cells. NK cells are part of innate immunity, which fights pathogens. NKT cells are intermediate between innate and adaptive immune systems. The innate immune system is needed to trigger adaptive immunity. Innate immune responses are well preserved in centenarians. NKT cells are found in thymus, liver, spleen and bone marrow. Remodeling of liver NKT cell functioning of centenarians is related to zinc and metallothionein (MT) protein activity.
Zinc is a mineral important in the functioning of innate and adaptive immune responses. Preservation of the innate immune activity depends on zinc availability within cells. MT plays a role in zinc storage and availability. In times of increased stress and inflammation, MT increases, binding zinc and making it less available for immune activity. Adequate zinc intake is essential.
NK cells are lymphocytes which can destroy tumor and virus-infected cells without antigen. NK cells cause programmed cell death (apoptosis) in abnormal cells, such as cancer or autoimmune cells. In patients of age 75-85, one study showed that the factor which most correlated with survival of a severe infection was increased activity of NK cells. Increased NK cell numbers can compensate for the reduced toxicity of NK cells with aging. Zinc deficiency reduces NK cell cytotoxicity (cell toxicity.)
The hormones of the hypothalamic-pituitary-gonadal axis alter the innate immune system during aging because of the normal hormone deficiencies of aging. Hormone treatment in old mice with T3, T4, melatonin, growth hormone, and IGF-1 restores NK cell cytotoxicity.
CONCLUSION: The balance of activity of the innate immune system between excessive immune response leading to inflammatory diseases and low response leading to infections in the elderly depends on MT homeostasis and zinc ion availability.
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PMID: 19408107.
Summary #442.
