Zinc, metallothioneins, immune responses, survival and ageing

Zinc is required as a catalytic, structural (zinc fingers) and regulatory i on. In this capacity, it is involved in many homeostatic mechanisms, includ ing immune responses. Metallothioneins (MTs) may play key roles because of their preferential binding to zinc especially in ageing. MTs protect from o xidative damage during transient stress conditions at young-adult age. This protection no longer exists in ageing and in age-related diseases (cancer and infections) because the stress condition is constant. As such, MTs may constantly deplete zinc from plasma and tissues. This phenomenon causes inc reased MTs levels on the one hand, but on the other hand induces low zinc i on bioavailability for normal immune responses. This may be particularly re levant for thymic functions and natural killer activity. Therefore MTs whic h are protective in young-adults may become dangerous in immune responses d uring ageing. Physiological supplementation of zinc in ageing corrects cent ral and peripheral immune defects, resulting prolonged survival and decreas ed mortality (50%) from infections and tumours, especially during middle ag e. Because of increased MT gene expression and protein levels in the liver and atrophic thymus of old mice, MTs are proposed as genetic markers of imm unosenescence.