Accurate Quantification of More Than 4000 Mouse Tissue Proteins Reveals Minimal Proteome Changes During Aging

Dirk M Walther,Matthias Mann

doi:10.1074/mcp.m110.004523

Abstract

The biological process of aging is believed to be the result of an accumulation of cellular damage to biomolecules. Although there are numerous studies addressing mutation frequencies, morphological or transcriptional changes in aging mammalian tissues, few have measured global changes at the protein level. Here, we present an in depth proteomic analysis of three brain regions as well as heart and kidney in mice aged 5 or 26 months, using stable isotope labeling of whole animals (SILAC mouse) and high resolution mass spectrometry. In the frontal cortex and hippocampal regions of the brain, more than 4200 proteins were quantitatively compared between age groups. Proteome differences between individual mice were observable within and between age groups. However, mean protein abundance changes of more than twofold between young and old mice were detected in less than 1% of all proteins and very few of these were statistically significant. Similar outcomes were obtained when comparing cerebellum, heart, and kidney between age groups. Thus, unexpectedly, our results indicate that aging-related effects on the tissue proteome composition at the bulk level are only minor and that protein homeostasis remains functional up to a relatively high age.

Highlights

In recent years, great progress has been made in the field of high resolution mass spectrometry (MS)-based proteomics, allowing for accurate identification of thousands of proteins (10 –13)
We extended the study to cerebellum, kidney, and heart muscle but in contrast to the previous experiments, lysates within age groups were pooled for each of these three tissues
Using high resolution mass spectrometry combined with the SILAC mouse technology, we performed the most comprehensive study of mammalian tissue aging at the proteome level to date

Summary

Introduction

Great progress has been made in the field of high resolution mass spectrometry (MS)-based proteomics, allowing for accurate identification of thousands of proteins (10 –13). We took advantage of the SILAC mouse technology and high resolution MS to study global effects of aging in mammalian tissues at the protein level. The Aging Tissue Proteomes of Frontal Cortex and Hippocampus—In frontal cortex and hippocampus, expression data for more than 4200 proteins of each four young and old mice were acquired individually.

Results

Conclusion