Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation

  1. Kelmer Sacramento, Erika ORCID logo
  2. Kirkpatrick, Joanna M
  3. Mazzetto, Mariateresa
  4. Baumgart, Mario
  5. Bartolome, Aleksandar
  6. Di Sanzo, Simone
  7. Caterino, Cinzia
  8. Sanguanini, Michele ORCID logo
  9. Papaevgeniou, Nikoletta
  10. Lefaki, Maria
  11. Childs, Dorothee
  12. Bagnoli, Sara
  13. Terzibasi Tozzini, Eva
  14. Di Fraia, Domenico
  15. Romanov, Natalie
  16. Sudmant, Peter ORCID logo
  17. Huber, Wolfgang
  18. Chondrogianni, Niki
  19. Vendruscolo, Michele ORCID logo
  20. Cellerino, Alessandro ORCID logo
  21. Ori, Alessandro ORCID logo

Download
s00424-021-02545-y.pdf 823,09KB
WeightNameValue
1000 Titel
  • Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation
1000 Autor/in
  1. Kelmer Sacramento, Erika |
  2. Kirkpatrick, Joanna M |
  3. Mazzetto, Mariateresa |
  4. Baumgart, Mario |
  5. Bartolome, Aleksandar |
  6. Di Sanzo, Simone |
  7. Caterino, Cinzia |
  8. Sanguanini, Michele |
  9. Papaevgeniou, Nikoletta |
  10. Lefaki, Maria |
  11. Childs, Dorothee |
  12. Bagnoli, Sara |
  13. Terzibasi Tozzini, Eva |
  14. Di Fraia, Domenico |
  15. Romanov, Natalie |
  16. Sudmant, Peter |
  17. Huber, Wolfgang |
  18. Chondrogianni, Niki |
  19. Vendruscolo, Michele |
  20. Cellerino, Alessandro |
  21. Ori, Alessandro |
1000 Erscheinungsjahr 2020
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2020-06-18
1000 Erschienen in
1000 Quellenangabe
  • 16(6)
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2020
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.15252/msb.20209596 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301280/ |
1000 Publikationsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • A progressive loss of protein homeostasis is characteristic of aging and a driver of neurodegeneration. To investigate this process quantitatively, we characterized proteome dynamics during brain aging in the short-lived vertebrate Nothobranchius furzeri combining transcriptomics and proteomics. We detected a progressive reduction in the correlation between protein and mRNA, mainly due to post-transcriptional mechanisms that account for over 40% of the age-regulated proteins. These changes cause a progressive loss of stoichiometry in several protein complexes, including ribosomes, which show impaired assembly/disassembly and are enriched in protein aggregates in old brains. Mechanistically, we show that reduction of proteasome activity is an early event during brain aging and is sufficient to induce proteomic signatures of aging and loss of stoichiometry in vivo. Using longitudinal transcriptomic data, we show that the magnitude of early life decline in proteasome levels is a major risk factor for mortality. Our work defines causative events in the aging process that can be targeted to prevent loss of protein homeostasis and delay the onset of age-related neurodegeneration.
1000 Sacherschließung
lokal Mice, Inbred C57BL [MeSH]
lokal Aging/metabolism [MeSH]
lokal RNA, Messenger/genetics [MeSH]
lokal Risk Factors [MeSH]
lokal Ribosomes/metabolism
lokal Brain/metabolism
lokal Mice, Inbred C57BL
lokal Aging/metabolism
lokal RNA, Messenger/metabolism
lokal Aging/genetics
lokal Protein Aggregates
lokal Proteasome Endopeptidase Complex/metabolism [MeSH]
lokal Ribosomes/metabolism [MeSH]
lokal RNA, Messenger/genetics
lokal RNA, Messenger/metabolism [MeSH]
lokal Ribosomal Proteins/genetics
lokal Protein Aggregates [MeSH]
lokal Transcriptome/genetics [MeSH]
lokal Aging/genetics [MeSH]
lokal Biophysical Phenomena [MeSH]
lokal Animals [MeSH]
lokal Biophysical Phenomena
lokal Reproducibility of Results [MeSH]
lokal Cyprinodontiformes/genetics [MeSH]
lokal Brain/metabolism [MeSH]
lokal Cyprinodontiformes/genetics
lokal Reproducibility of Results
lokal Ribosomal Proteins/genetics [MeSH]
lokal Transcriptome/genetics
lokal Ribosomal Proteins/metabolism [MeSH]
lokal Animals
lokal Ribosomal Proteins/metabolism
lokal Risk Factors
lokal Proteasome Endopeptidase Complex/metabolism
1000 Bestandteil von frl:6446972
1000 Fächerklassifikation (DDC)
1 Dateiname s00424-021-02545-y.pdf
2 Format application/pdf
3 Größe 823,09KB
4 MD5 51234edeedd0ec03d058fcfc28c70dcc
1000 Liste der Beteiligten
  1. https://orcid.org/0000-0002-3336-982X|https://frl.publisso.de/adhoc/uri/S2lya3BhdHJpY2ssIEpvYW5uYSBN|https://frl.publisso.de/adhoc/uri/TWF6emV0dG8sIE1hcmlhdGVyZXNh|https://frl.publisso.de/adhoc/uri/QmF1bWdhcnQsIE1hcmlv|https://frl.publisso.de/adhoc/uri/QmFydG9sb21lLCBBbGVrc2FuZGFy|https://frl.publisso.de/adhoc/uri/RGkgU2Fuem8sIFNpbW9uZQ==|https://frl.publisso.de/adhoc/uri/Q2F0ZXJpbm8sIENpbnppYQ==|https://orcid.org/0000-0002-7142-3807|https://frl.publisso.de/adhoc/uri/UGFwYWV2Z2VuaW91LCBOaWtvbGV0dGE=|https://frl.publisso.de/adhoc/uri/TGVmYWtpLCBNYXJpYQ==|https://frl.publisso.de/adhoc/uri/Q2hpbGRzLCBEb3JvdGhlZQ==|https://frl.publisso.de/adhoc/uri/QmFnbm9saSwgU2FyYQ==|https://frl.publisso.de/adhoc/uri/VGVyemliYXNpIFRvenppbmksIEV2YQ==|https://frl.publisso.de/adhoc/uri/RGkgRnJhaWEsIERvbWVuaWNv|https://frl.publisso.de/adhoc/uri/Um9tYW5vdiwgTmF0YWxpZQ==|https://orcid.org/0000-0002-9573-8248|https://frl.publisso.de/adhoc/uri/SHViZXIsIFdvbGZnYW5n|https://frl.publisso.de/adhoc/uri/Q2hvbmRyb2dpYW5uaSwgTmlraQ==|https://orcid.org/0000-0002-3616-1610|https://orcid.org/0000-0003-3834-0097|https://orcid.org/0000-0002-3046-0871
1000 Hinweis
  • Metadata provieded by: LIVIVO search scope life sciences (http://z3950.zbmed.de:6210/livivo), Crossref Unified Resource API (https://api.crossref.org/swagger-ui/index.html), to.science.api (https://frl.publisso.de/), ZDB JSON-API (beta) (https://zeitschriftendatenbank.de/api/), lobid - Dateninfrastruktur für Bibliotheken (https://lobid.org/resources/search)
1000 Label
1000 Objektart article
1000 Beschrieben durch
1000 @id frl:6446973.rdf
1000 Erstellt am 2023-04-28T14:43:30.522+0200
1000 Erstellt von 336
1000 beschreibt frl:6446973
1000 Zuletzt bearbeitet 2025-06-30T07:16:38.750+0200
1000 Objekt bearb. Mon Jun 30 07:16:38 CEST 2025
1000 Vgl. frl:6446973
1000 Oai Id
  1. oai:frl.publisso.de:frl:6446973 |
1000 Sichtbarkeit Metadaten public
1000 Sichtbarkeit Daten public
1000 Gegenstand von

View source