Discovery of Age-Related Protein Folding Stability Differences in the Mouse Brain Proteome.


Journal Article

Described here is the application of thermodynamic stability measurements to study age-related differences in the folding and stability of proteins in a rodent model of aging. Thermodynamic stability profiles were generated for 809 proteins in brain cell lysates from mice, aged 6 (n = 7) and 18 months (n = 9) using the Stability of Proteins from Rates of Oxidation (SPROX) technique. The biological variability of the protein stability measurements was low and within the experimental error of SPROX. A total of 83 protein hits were detected with age-related stability differences in the brain samples. Remarkably, the large majority of the brain protein hits were destabilized in the old mice, and the hits were enriched in proteins that have slow turnover rates (p < 0.07). Furthermore, 70% of the hits have been previously linked to aging or age-related diseases. These results help validate the use of thermodynamic stability measurements to capture relevant age-related proteomic changes and establish a new biophysical link between these proteins and aging.

Full Text

Duke Authors

Cited Authors

  • Roberts, JH; Liu, F; Karnuta, JM; Fitzgerald, MC

Published Date

  • December 2016

Published In

Volume / Issue

  • 15 / 12

Start / End Page

  • 4731 - 4741

PubMed ID

  • 27806573

Pubmed Central ID

  • 27806573

Electronic International Standard Serial Number (EISSN)

  • 1535-3907

International Standard Serial Number (ISSN)

  • 1535-3893

Digital Object Identifier (DOI)

  • 10.1021/acs.jproteome.6b00927


  • eng