Proteomics

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Derailed protein turnover in the aging mammalian brain


ABSTRACT: Efficient protein turnover is essential for cellular homeostasis and organ function. Loss of proteostasis is a hallmark of aging, which culminates as a severe reduction in protein turnover rates. To investigate changes in protein turnover dynamics as a function of age, we performed continuous in vivo metabolic stable isotope labeling in mice along the aging continuum. First, we discovered that the brain proteome uniquely experiences dynamic global turnover fluctuations during aging compared to heart and liver tissue. Second, in the brain proteome, global protein turnover trends across aging displayed sex-specific differences that were tightly tied to their cellular compartments. Next, parallel analyses of the insoluble proteome revealed that distinct cellular compartments experience hampered turnover, in part due to misfolding. Finally, we discovered that age-associated fluctuations in the activity of the ubiquitin proteasome system were linked to the turnover of the catalytic core subunits. Taken together, our study provides a proteome-wide atlas of protein turnover across the aging continuum and highlights a link between the turnover of individual proteasome subunits and the age-associated decline in proteosome activity.

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Jeffrey N. Savas, PhD  

PROVIDER: MSV000092174 | MassIVE | Thu Jun 15 07:31:00 BST 2023

SECONDARY ACCESSION(S): PXD043023

REPOSITORIES: MassIVE

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