Does promoter methylation of the SLC30A5 (ZnT5) zinc transporter gene contribute to the ageing-related decline in zinc status?

摘要

A decline in Zn status with ageing may contribute to the development of frailty, including impaired immune function, and increased incidence of age-related degenerative diseases. This decline may be a result of reduced dietary Zn intake and/or impaired Zn absorption in the gut. The Zn transporter ZnT5 may play a key role in the absorption of dietary Zn. The corresponding gene (SLC30A5) has a CpG island in its promoter region, so could be regulated by epigenetic mechanisms. It is hypothesised that methylation of the SLC30A5 promoter region is increased with age and that a resulting reduction in ZnT5 expression contributes to the decline in Zn status observed with ageing. This hypothesis has been addressed through (1) studies of effects of SLC30A5 promoter methylation on gene expression in vitro and (2) in vivo measurements of the DNA methylation status of this gene domain. It has been established in vitro that methylation of the human SLC30A5 promoter region results in reduced expression of an associated reporter gene. Second, this gene region shows variable levels of methylation in vivo. Correlation between the level of methylation at this locus and age would support the hypothesis that age-related hypermethylation of this region has the potential to modulate dietary Zn absorption. This premise is being investigated by analysis of additional samples from a human adult cohort to test the hypothesis that methylation of the SLC30A5 promoter region contributes to the age-related decline in Zn status.