, Volume 1, Issue 2, pp 133-143

Zinc, metallothioneins, immune responses, survival andageing

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Abstract

Zinc is required as a catalytic, structural (zincfingers) and regulatory ion. In this capacity, it isinvolved in many homeostatic mechanisms, includingimmune responses. Metallothioneins (MTs) may play keyroles because of their preferential binding to zincespecially in ageing. MTs protect from oxidativedamage during transient stress conditions atyoung-adult age. This protection no longer exists inageing and in age-related diseases (cancer andinfections) because the stress condition is constant.As such, MTs may constantly deplete zinc from plasmaand tissues. This phenomenon causes increased MTslevels on the one hand, but on the other hand induceslow zinc ion bioavailability for normal immuneresponses. This may be particularly relevant forthymic functions and natural killer activity.Therefore MTs which are protective in young-adults maybecome dangerous in immune responses during ageing.Physiological supplementation of zinc in ageingcorrects central and peripheral immune defects,resulting prolonged survival and decreased mortality (50%) frominfections and tumours, especially during middle age.Because of increased MT gene expression and proteinlevels in the liver and atrophic thymus of old mice,MTs are proposed as genetic markers of immunosenescence.