Derailed protein turnover in the aging mammalian brain
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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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