ArticleMolecular systems biology2020
Reduced proteasome activity in the aging brain results in ribosome stoichiometry loss and aggregation.
Article in Molecular systems biology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 141 papers, 2 of them syntheses that pooled it.
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Who cites it
141 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Shift of the insoluble content of the proteome in the aging mouse brain.Proceedings of the National Academy of Sciences of the United States of America · 2023Pooled it
- Association between Hepatocellular Carcinoma Recurrence and Graft Size in Living Donor Liver Transplantation: A Systematic Review.International journal of molecular sciences · 2023Pooled it
- Predicting and finding geroprotective compounds through modulating conserved longevity-associated aging modules.Science advances · 2026Article
- Proteostasis and ageing dissidence.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2026Review
- Error-prone translation as a driver of proteostasis collapse and neurodegeneration.Neural regeneration research · 2026Article
- The Hallmarks of Aging: From Molecular Mechanisms to Clinical Translation.International journal of molecular sciences · 2026Review
- Combating ageing beyond the cell: Emerging roles of extracellular proteostasis.The FEBS journal · 2026Review
- Protein thiol alterations drive pathologic liquid-liquid phase separation in the aging brain.Nature structural & molecular biology · 2026Article
- SIEVEseq: unified differential expression, variability, and skewness analyses using RNA-Seq data.DNA research : an international journal for rapid publication of reports on genes and genomes · 2026Article
- Reductive death is averted by a conserved de novo lipogenic switch.Molecular cell · 2026Article
- Ontological Analysis of Brain Proteostasis Highlights the Sex-Dependent Trajectory of ApoE Isoform-Specific Regulation.bioRxiv : the preprint server for biology · 2026Article
- Proteasome Dysfunction and Aggregation-Prone Proteins in Neurodegenerative Diseases: From Mechanisms to Therapeutic Opportunities.International journal of molecular sciences · 2026Review
- Histone modification dynamics in brain aging: unlocking therapeutic potential.Cell death & disease · 2026Review
- Article
- Engulfment by brain macrophages in a short-lived vertebrate.bioRxiv : the preprint server for biology · 2026Article
- Oxidative stress causes a reversible decrease of deubiquitylases activity in old vertebrate brains.Nature communications · 2026Article
- Shifts in protein aggregate stability define proteostasis decline in the aging human brain.bioRxiv : the preprint server for biology · 2026Article
- Aging-associated decline of phosphatidylcholine synthesis is a malleable trigger of natural mitochondrial aging.Nature communications · 2026Article
- Aging clocks delineate neuron types vulnerable or resilient to neurodegeneration and identify neuroprotective interventions.Nature aging · 2026Article
- Spontaneous aging-associated inflammation and genome instability in the immune system of turquoise killifish.Nature aging · 2026Article
81 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors.
Funding
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Abstract
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.
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