Ageing is an inevitable biological process with gradual and spontaneous biochemical and physiological changes and increased susceptibility to diseases. Nutritional zinc may remodel these change with subsequent healthy ageing, because zinc improves the inflammatory/immune response as shown by “in vitro” and “in vivo” studies. However, in ageing, the zinc daily dietary intake is reduced than that one recommended by the RDA. Many causes can be involved: among them, inadequate mastication, psychosocial factors, drugs interactions, altered cellular processes [zinc transporters and Metallothioneins (MT)]. These processes are very relevant because the intracellular zinc homeostasis is regulated by buffering MT and zinc transporters assigning to zinc a role of “second messenger”. Physiological zinc supplementation in elderly improves these functions with however contradictory data. Therefore, the choice of old subjects for zinc supplementation has to be better considered 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. The genetic variations of IL-6 -174G/C locus when associated with those ones of MT1A +647A/C locus are useful tools for the choice of old people for zinc supplementation because improving the inflammatory/immune response, suggesting the relevance of zinc-MT gene interaction for healthy ageing and longevity.