For the past century, and particularly over the past few decades, life expectancy increased significantly and according to the World Health Organisation it continues growing at fast rate of about 6% in 20 years, with suggestions that it may reach 100 years this century. This is attributed to advances in healthcare, better nutrition and lifestyle changes. Increased longevity, with a high quality of life, is desirable not only for personal life satisfaction but also for reducing healthcare costs and for increasing socioeconomic contributions of individuals in countries with ageing population demographics, including Europe. Adequate nutrition plays a key role in maintaining cellular functions within normal limits. Microelements such as zinc (Zn) and copper (Cu) are essential for life and are involved in normal functioning of the human body. Our body tissues consist of cells and, through the functioning of channels and transporters, influx and efflux of Zn and Cu are tightly controlled.
At a molecular level, Zn and Cu play structural, regulatory and catalytic roles in thousands of proteins. Zn in cells protects against oxidation by controlling the production of reducing agents and stabilising molecules that contain oxygen-reactive groups. Cu can exist in both oxidised and reduced forms. In living cells, Cu can also participate in unwanted redox reactions, generating harmful free radicals. Damage caused by over-oxidation is difficult for cells to counteract and repair and so damage is cumulative over time. This process at a whole-body level contributes to ageing but at a cellular level accelerates senescence.
The mechanisms responsible for dysregulation of these metals require thorough investigation from molecules to the whole body. However, despite the importance of a holistic approach to this subject, such studies are limited. The MILEAGE Project aimed to understand the molecular mechanisms by which ageing affects Zn and Cu absorption and excretion, and also their functional roles. The specific objectives targeted age-related alterations in homeostasis and control of these metals on multiple levels, from gut microbiota to groups of volunteers and patients, while testing the expression of genes and the function of proteins. In accordance with the RISE action of intensive scientific exchange, the Project provided extensive multifactorial training to researchers from organizations in different countries and promoted the acquisition of unique experience and knowledge.
