Those 'morning after feelings' get worse as you get older — ageing certainly has its problems, but the body can protect against some of these. Richard Van Etten and colleagues show that the antioxidant peroxiredoxin 1 (Prdx1) is an important defence, which protects ageing mice from the harmful effects of oxidants.

The authors generated Prdx1-null mice, which were viable and fertile but had significantly shortened survival compared to wild-type littermates. Premature death was caused by haemolytic anaemia and formation of cancers, including B and T lymphomas, histiocytic malignancies and epithelial and mesenchymal tumours. These diseases were increased in heterozygotes and Prdx1 was found in most wild-type tissues, but was low or undetectable in tumours. So, Prdx1 seems to act as a tumour suppressor. Examinations in heterozygotes did not reveal structural rearrangement or loss of the remaining Prdx1 allele, indicating that mutations or epigenetic mechanisms cause the loss of Prdx1 expression. But what mechanisms cause tumour formation in the Prdx1−/− mice?

Prdx1−/− mouse embryonic fibroblasts (MEFs) in vitro proliferated more slowly, were more sensitive to oxidants and had greater concentrations of peroxide-induced cellular reactive oxygen species (ROS) than wild-type MEFs. In addition, Prdx1−/− MEFs had higher basal and peroxide-induced concentrations of 8-oxoguanine — an oxidative DNA lesion that causes mutations. Collectively, this indicates that loss of Prdx1 increases susceptibility to cancer by increasing sensitivity to oxidants, cellular ROS and oxidative DNA damage. Prdx1 has also been identified as an enhancer of natural killer (NK)-cell activity and NK cells are important for protecting against tumorigenesis. So, the authors examined NK cells isolated from Prdx1−/− mice and found decreased lytic activity towards the murine NK-sensitive T-lymphoma cell line YAC-1. Erythrocytes stimulate the cytotoxic activity of NK cells, but Prdx1−/− erythrocytes were not as effective as wild-type erythrocytes at enhancing cytotoxic activity of wild-type NK cells. Conversely, wild-type erythrocytes had little stimulatory activity on Prdx1−/− NK cells, indicating that Prdx1 is required in both NK cells and non-immune cells for optimal NK function.

So, Prdx1 is directly implicated in tumour suppression in ageing mice. This work is a first step towards identifying the mechanisms that predispose Prdx1−/− mice to cancer and understanding how antioxidant pathways protect against tumour formation.