The pivotal role played by zinc-gene interaction in affecting the inflammatory response mediated by IL-6 in ageing, successful ageing (nonagenarians) and the most common age-related diseases is now recognized. Contradictory data emerging from association studies of IL-6 polymorphisms with longevity and chronic age-related diseases seem to arise from the interaction of this inflammatory pathway with dietary habits. Similar conclusions are expected to arise from association studies with the frailty syndrome. Some polymorphisms of genes related to vitamin B12 availability have been already found to be associated with frailty suggesting a possible link among diet-gene interaction and frailty in old age. Other studies in this field are urgently required because of their high potential for suggesting strategies in the care and prevention of frailty in ageing through dietary interventions, in which nutrient zinc may play a pivotal role taking into account that the high copper to zinc ratio is a significant index of the mortality in older people.