ArticleNature aging2024
A mortality timer based on nucleolar size triggers nucleolar integrity loss and catastrophic genomic instability.
Article in Nature aging, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Proteostasis of organelles in aging and disease.The FEBS journal · 2026Review
- The entropic view of aging: from thermodynamics to biology.Life medicine · 2026Article
- Article
- Embryo-scale Visual Cell Sorting reveals a conserved transcriptomic signature of nucleolar size linked to proteostasis.bioRxiv : the preprint server for biology · 2026Article
- Resolving Sub-Nuclear Architecture from Compartments to Functional Domains.International journal of molecular sciences · 2026Review
- Nucleolar Dynamics During Oogenesis.bioRxiv : the preprint server for biology · 2026Article
- Isobaric quantitative proteomics reveals altered extracellular matrix, cytoskeletal, and degradation pathways in glaucomatous trabecular meshwork cells.Scientific reports · 2026Article
- Cell enlargement drives aging-associated proteome remodeling and shortens replicative lifespan.bioRxiv : the preprint server for biology · 2026Article
- Article
- Nucleolar expansion: A biomolecular condensate mortality timer.Geromedicine · 2026Article
- Associations of rDNA copy numbers and global DNA methylation with myocardial infarction.Frontiers in cardiovascular medicine · 2026Article
- Fluorescence lifetime clocks quantify senescence and aging.Nature aging · 2025Article
- Overexpression of Ssd1 and calorie restriction extend yeast replicative lifespan by preventing deleterious age-dependent iron uptake.bioRxiv : the preprint server for biology · 2025Article
- Nuclear and genome dynamics underlying DNA double-strand break repair.Nature reviews. Molecular cell biology · 2025Review
- Remodeling, compartmentalization, and degradation: a trifecta for organelle quality control during gametogenesis.Current opinion in genetics & development · 2025Review
Corrections and comments
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Authors and funding
2 authors.
Funding
Abstract
Genome instability is a hallmark of aging, with the highly repetitive ribosomal DNA (rDNA) within the nucleolus being particularly prone to genome instability. Nucleolar enlargement accompanies aging in organisms ranging from yeast to mammals, and treatment with many antiaging interventions results in small nucleoli. Here, we report that an engineered system to reduce nucleolar size robustly extends budding yeast replicative lifespan in a manner independent of protein synthesis rate or rDNA silencing. Instead, when nucleoli expand beyond a size threshold, their biophysical properties change, allowing entry of proteins normally excluded from the nucleolus, including the homologous recombinational repair protein Rad52. This triggers rDNA instability due to aberrant recombination, catastrophic genome instability and imminent death. These results establish that nucleolar expansion is sufficient to drive aging. Moreover, nucleolar expansion beyond a specific size threshold is a mortality timer, as the accompanying disruption of the nucleolar condensate boundary results in catastrophic genome instability that ends replicative lifespan.
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