# Integrated liver and serum proteomics uncover sexual dimorphism and alteration of several immune response proteins in an aging Werner syndrome mouse model

## TL;DR

This study finds that aging in a mouse model of Werner syndrome shows sex-based differences in liver and blood proteins, especially in immune and metabolic processes.

## Contribution

The study reveals sexual dimorphism and immune-related protein changes in aging Werner syndrome mice using integrated proteomics.

## Key findings

- Sexual dimorphism in proteomic profiles was observed in both liver and serum, regardless of age or genotype.
- Males showed age- and genotype-dependent changes in lipid and fatty acid metabolism proteins.
- Both sexes showed immune system alterations, with increased immunoglobulins linked to fatty liver progression.

## Abstract

Werner syndrome (WS) is a progeroid disorder caused by mutations in a protein containing both a DNA exonuclease and DNA helicase domains. Previous studies indicated that males lacking the helicase domain of the Wrn protein orthologue exhibited hepatic transcriptomic and metabolic alterations. In this study, we used a label-free liquid chromatography-tandem mass spectrometry approach to uncover proteins abundance associated with specific biological processes that differed depending on the age (four or ten months) and/or the genotype (wild type or Wrn mutant) in the serum and liver of mice. Principal component analysis of the proteomic data from both serum and hepatic tissue revealed a sexual dimorphism regardless of the age and the genotype of the mice. Moreover, although all Wrn mutant mice exhibited fatty liver by the age of ten months, a significant age and genotype dependent enrichment of proteins involved in lipid and fatty acid metabolic processes were uncovered only in males. Also, a genotype dependent increase in serum oxidant detoxification processes was observed in the serum of Wrn mutant males. Despite these sexual differences, several aspects of the immune system were affected in both females and males. Finally, an increase of specific immunoglobulin molecules was common in the liver and serum of both older Wrn mutant females and males. Such results suggest that specific immunoglobulin variants maybe associated with fatty liver progression in WS.