Proceedings of the Nutrition Society

Postgraduate Symposium

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

Conference on ‘Multidisciplinary approaches to nutritional problems’

on 30 June–3 July 2008, The Summer Meeting of the Nutrition Society, was held at the University of Nottingham.

L. J. Coneywortha1a2 c1, J. C. Mathersa1a3 and D. Forda1a2

a1 Human Nutrition Research Centre, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK

a2 Institute for Cell and Molecular Biosciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK

a3 Institute for Ageing and Health, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK

Abstract

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.

(Online publication February 27 2009)

Correspondence:

c1 Corresponding author: L. J. Coneyworth, fax +44 191 222 7424, email L.J.Coneyworth@newcastle.ac.uk