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

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.