Background

Diet and aging are linked to the development of insulin resistance a condition that is in turn linked to numerous diseases including stroke, cancer, cardiovascular disease, Alzheimer’s disease and type 2 diabetes. Surprisingly, a recent study showed that aging in mice had relatively little effect on the total proteome of brain, kidney and heart (Walther & Mann, 2010). In the current study we wanted to extend this analysis to compare the effects of ageing per se with that of diet on the total proteome. In our study we have used a more metabolically relevant tissue, the liver.

Materials and Methods

We studied mice fed a chow diet at 20 (C20) and 60 (C60) weeks and mice fed a HFD at 60 (HF60) weeks. To measure changes in protein abundance induced by age or diet we performed MS-based proteomics on individual livers from 8x C20, 8x C60 and 8x HF60 mice. MS spectra were analysed by MaxQuant and differential expression and pathway over representation tests were performed.

Results and conclusions

We acquired quantitative data on 5,906 proteins in liver. To compare the effect of aging and diet on the liver proteome, we compared the number of differentially expressed (DE) proteins generated from two comparisons. Effects of age (C20 and C60) and diet (C60 and H60) on protein expression were assessed. Relatively few (n=14) proteins showed DE in livers from old versus young animals consistent with studies in brain, heart and kidney. Strikingly, the number of DE proteins (Fold change> 1.5) between livers from chow versus fat fed animals was 10 fold higher indicating that diet has a much more potent effect on the total proteome than does age alone. Pathway analysis of DE genes showed a down regulation in cholesterol biosynthesis and the downstream modifications of cholesterol such as bile acids. Studies are now being performed to validate these findings.