Journal Article

DZNE-2022-01111

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Protein lifetimes in aged brains reveal a proteostatic adaptation linking physiological aging to neurodegeneration

Kluever, V. ; Russo, B. (First author)DZNE* ; Mandad, S. ; Kumar, N. H. ; Alevra, M. ; Ori, A. ; Rizzoli, S. O. ; Urlaub, H. ; Schneider, A. (Last author)DZNE* ; Fornasiero, E. F.

2022
Assoc. Washington, DC [u.a.]

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Please use a persistent id in citations: doi:10.1126/sciadv.abn4437

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 proteostasis that correlates to parsimonious turnover of proteins with high biosynthetic costs, revealing an overall metabolic adaptation that preludes neurodegeneration. Our findings suggest that future therapeutic paradigms, aimed at addressing these metabolic adaptations, might be able to delay NDD onset.

Keyword(s): Aging: metabolism (MeSH) ; Animals (MeSH) ; Brain: metabolism (MeSH) ; Mice (MeSH) ; Neurodegenerative Diseases: etiology (MeSH) ; Neurodegenerative Diseases: metabolism (MeSH) ; Proteolysis (MeSH) ; Proteomics (MeSH)

Note: (CC BY 4.0)

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Contributing Institute(s):

1. Translational Dementia Research (Bonn) (AG Schneider)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2022

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