Zinc, metallothioneins and immunosenescence

Abstract

Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. The nutritional factor, zinc, may remodel these changes with subsequent healthy ageing, because zinc improves the inflammatory/immune response as shown by in vitro and in vivo studies. The intracellular zinc homeostasis is regulated by buffering metallothioneins (MT) and zinc transporters (ZnT and ZIP families) that mediate the intracellular zinc signalling assigning to zinc a role of 'second messenger'. In ageing, the intracellular zinc homeostasis is altered, because high MT are unable to release zinc and some zinc transporters deputed to zinc influx (ZIP family) are defective leading to low intracellular zinc content for the immune efficiency. Physiological zinc supplementation in the elderly improves these functions. However, the choice of old subjects for zinc supplementation has to be performed in relation to the specific genetic background of MT and IL-6, because the latter is involved both in MTmRNA and in intracellular zinc homeostasis. Old subjects carrying GG genotypes (C-carriers) in the IL-6 -174G/C locus display high IL-6, low intracellular zinc content, impaired innate immunity and enhanced MT. Old subjects carrying GC and CC genotypes (C + carriers) display satisfactory intracellular zinc content, adequate innate immunity and are more prone to reach longevity. Zinc supplementation in old C-carriers restores natural killer cell cytotoxicity and zinc status. The genetic variations of the IL-6 -174G/C locus when associated with those of the MT1A + 647A/C locus are useful tools for the choice of old people for zinc supplementation.

Nutritional and Physical Activity Interventions to Improve Immunity

“…175 The suboptimal status of macronutrients and micronutrients often found in the older population is suggested to exacerbate immunosenescence. [176][177][178] The majority of nutritional interventions to date have focused on use of dietary lipids (n-3, n-6 polyunsaturated fatty acids) and micronutrients such as vitamin E, carotenoids, and zinc, all of which are essential in mounting immune responses. [178][179][180] However, evidence for the effects of these nutritional supplementation strategies in impacting on immunosenescence is equivocal.…”

“…181 The inconsistent effects in the literature with micronutrient supplementation are most likely due to variance in dosage between studies and/or the initial nutritional status of individuals. 177 Although some studies have shown single and/or multivitamin or mineral supplementation can reverse age related declines in immune parameters, the risks associated with over-supplementation must be recognized whereby an approach to "right dose" rather than "megadose" is required. 182 As highlighted for the younger adult population, it is unlikely that micronutrient supplementation beyond the level required to correct for dietary insufficiency will provide any further benefit.…”

Zinc, metallothioneins and immunosenescence: effect of zinc supply as nutrigenomic approach

“…A number of publications have reported the effect of zinc supplementation upon various immune parameters in elderly with different doses and length of period treatment (see exhaustive review Mocchegiani et al 2010). The most important parameter affected by physiological or slightly above (i.e.…”

Mammalian Metallothionein-3: New Functional and Structural Insights

“…Aging, a major risk factor for neurodegenerative disorders, is accompanied with structural, chemical, functional, neuropsychological, and genetic changes, with increased susceptibility to diseases and cognitive impairments [1]. In the normal brain, a high concentration of essential transition metal ions such as zinc, copper, and iron is present.…”