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Description of the Workplan

General description and milestones

The project ZINCAGE foresees the study of the zinc metabolism in order to reach healthy ageing. For this purpose, different approaches will be considered at genetic, biochemical, molecular and cellular levels with a final target on the efficiency of the immune system.

The loss of this trace element provokes a general derangement of systems with subsequent weakness of the old organism to respond to oxidative stress induced by external damaging agents allowing the appearance of age-related degenerative diseases.

However, the loss of zinc is not equal in all old individuals at, at the same time, the zinc deficiency is strictly correlated to free zinc ion bioavailability. Indeed, it may occur that some individuals are “high responders” to oxidative stress despite the content of zinc into the circulation is low.

It depends by some stress related-proteins involved in the distribution and in the metabolism of zinc ions. The correct functions of these proteins lead to a satisfactory zinc ion bioavailability with subsequent good functioning of the immune system. This is the case in transient stress as it may occur in young-adult age and with a great surprising in successful ageing (nonagenarian/centenarian subjects).

Therefore, the zinc-dependent stress-related proteins play a pivotal role in zinc metabolism to reach health longevity. Taking into account a different distribution of zinc ion bioavailability between normal ageing and successful ageing, a genetic background of these stress-related proteins might exist leading to a different distribution of zinc ion bioavailability within the ageing population.

For this reason, a zinc supplementation is also foreseen in ZINCAGE exclusively in aged people with a defect in zinc metabolism at genetic level. Because of the relevance of zinc in cognitive functions, also these last aspects will be considered in the project before and after zinc supplementation for a complete healthy ageing.

This will provide essential knowledge for recommending zinc supplementation levels in different populations in order to avoid zinc toxicity and enhance food safety. Thus, the project ZINCAGE is broken down into six work packages and will be conducted by six work package leaders in collaboration with other active partners.

Dividing the project into six work packages is mainly based on the content of the specific research.

Each of the six work packages constitutes a specific and complementary sub project involving the participation of several partners, bringing in their particular expertise in genetic or biochemical or molecular and cellular biology.

Each partner will have a specific task in the research and in developing new technologies and innovative activities. The leaders of each work package will be also involved in the management activity because belonging to the Steering Committee and a specific workpackage in the management activity is present in ZINGAGE. Moreover, this project foresees also a zinc supplementation in selected old people with genetic marked zinc-deficiency in order to promote healthy ageing and longevity.

The decision of this supplementation will be taken after a meeting of all partners at 22nd month on the basis of obtained results. Therefore, the main and crucial milestones (see list) for all the workpackages are go/no go decision for zinc supplementation in elderly.