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.
Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
Julia H
JH
Roberts
Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
Fang
F
Liu
Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
Jaret M
JM
Karnuta
Department of Chemistry, Duke University , Durham, North Carolina 27708, United States.
Michael C
MC
Fitzgerald
D000375:Aging; D000818:Animals; D001921:Brain / Q000378:metabolism*; D051379:Mice; D017510:Protein Folding; D055550:Protein Stability; D020543:Proteome / Q000737:chemistry*
D020543:Proteome
SPROX; aging; chemical denaturation; iTRAQ; mass spectrometry; proteomics