Metallome evolution in ageing C. elegans and a copper stable isotope perspective

Ageing is accompanied by important chemical deregulations resulting in bodily metal imbalances. The way and extent to which these deregulations are associated with ageing processes are however poorly understood and their use as potential biomarkers of ageing has not been investigated. In this study, we report whole-body elementary concentrations and copper and zinc isotopic compositions of Caenorhabditis elegans in ageing wild type (i.e.'normal'-lived) and mutant (i.e. short and long-lived) strains. We show that the strains are characterized by different levels of mutation-related variations such as in phosphorus and magnesium as well as in zinc isotopic composition. During ageing, strains are affected by elemental age-related variations, such as an increase in calcium and iron concentrations and a decrease in the copper isotopic composition and concentration for long-lived mutants. The deregulated metabolism of copper seems to be connected to ageing probably in association with the production of reactive oxygen species. We emphasize that the copper stable isotope composition could serve as a biomarker of normal or accelerated ageing in the future.