Proteomics

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Precisely measured protein lifetimes in the brain of aged mice

ABSTRACT: Aging, which is associated with protein homeostasis defects, is one of the most prominent risk factors for neurodegenerative disorders and the regulation of protein homeostasis is essential for brain health. While several studies have addressed changes in protein abundance due to aging, little is known about differences in protein stability in the mammalian brain proteome. In particular, pre-symptomatic alterations of protein stability might be instrumental for understanding the pathological alterations that occur during neurodegeneration. To explore these alterations, we measured proteome turnover with a pulse-SILAC approach in aged mice from total cortex and cerebellum homogenates and from the respective synaptic-enriched fraction. We compared the stability of young and aged proteomes. Our analyses revealed several differences and the large dataset that we created will serve as a resource for the community to develop approaches that explore these alterations with diagnostic and therapeutic purposes.

INSTRUMENT(S): Q Exactive HF

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Brain

SUBMITTER: Verena Klüver  

LAB HEAD: Eugenio F. Fornasiero

PROVIDER: PXD023994 | Pride | 2022-06-09

REPOSITORIES: Pride

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OldMice_Ctx-SF-14d-1_1.raw Raw
OldMice_Ctx-SF-14d-1_10.raw Raw
OldMice_Ctx-SF-14d-1_11.raw Raw
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Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration.

Kluever Verena V   Russo Belisa B   Mandad Sunit S   Kumar Nisha Hemandhar NH   Alevra Mihai M   Ori Alessandro A   Rizzoli Silvio O SO   Urlaub Henning H   Schneider Anja A   Fornasiero Eugenio F EF  

Science advances 20220520 20

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 incre  ...[more]

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