Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration.

ABSTRACT: Aging is a prominent risk factor for neurodegenerative disorders (NDDs); however, the molecular mechanisms rendering the aged brain particularly susceptible to neurodegeneration remain unclear. Here, we aim to determine the link between physiological aging and NDDs by exploring protein turnover using metabolic labeling and quantitative pulse-SILAC proteomics. By comparing protein lifetimes between physiologically aged and young adult mice, we found that in aged brains protein lifetimes are increased by ~20% and that aging affects distinct pathways linked to NDDs. Specifically, a set of neuroprotective proteins are longer-lived in aged brains, while some mitochondrial proteins linked to neurodegeneration are shorter-lived. Strikingly, we observed a previously unknown alteration in proteosta

SUBMITTER: Kluever V 

PROVIDER: S-EPMC9122331 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature