Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4
Open accessAbstract
In nearly every organism studied, reduced caloric intake extends life span. In yeast, span extension from dietary restriction is thought to be mediated by the highly conserved, nutrient-responsive target of rapamycin (TOR), protein kinase A (PKA), and Sch9 kinases. These kinases coordinately regulate various cellular processes including stress responses, protein turnover, cell growth, and ribosome biogenesis. Here we show that a specific reduction of 60S ribosomal subunit levels slows aging in yeast. Deletion of genes encoding 60S subunit proteins or processing factors or treatment with a small molecule, which all inhibit 60S subunit biogenesis, are each sufficient to significantly increase replicative life span. One mechanism by which reduced 60S subunit levels leads to life span extension is through induction of Gcn4, a nutrient-responsive transcription factor. Genetic epistasis analyses suggest that dietary restriction, reduced 60S subunit abundance, and Gcn4 activation extend yeast life span by similar mechanisms.
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Reducing ribosome subunits or interfering with the TOR/ribosomal protein S6 kinase pathway changes lifespan in many species, including mammals.
“Depletion of ribosome subunits or interference with the target of rapamycin/ribosomal protein S6 kinase pathway, which functions to activate protein translation, were found to alter the lifespan of a variety of species including mammals (54–56).”
From Controlled DNA double-strand break induction in mice reveals post-damage transcriptome stability (2016) · cites this paper as [56]
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- Authors
- Steffen, K. K., MacKay, V. L., Kerr, E. O., Tsuchiya, M., Hu, D., Fox, L. A., Dang, N., Johnston, E. D., Oakes, J. A., Tchao, B. N., Pak, D. N., Fields, S., Kennedy, B. K., & Kaeberlein, M.
- Affiliations
- University of Washington (US)
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kennedy, Brian K.
- Kaeberlein, Matt
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-04
- Volume
- 133
- Issue
- 2
- Pages
- 292-302
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC2749658
- OpenAlex
- W2160718564
- Cited by
- 465
- References
- 2
- Citations by year
- 2026: 13 · 2025: 14 · 2024: 22 · 2023: 19 · 2022: 16 · 2021: 22 · 2020: 31 · 2019: 28 · 2018: 21 · 2017: 28 · 2016: 31 · 2015: 26 · 2014: 25 · 2013: 28 · 2012: 30
- FWCI
- 10.65
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 1969 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Ellison Medical Foundation
- National Institutes of Health (R01 AG024287, P30 AG013280)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- replicative lifespan, 60S ribosomal subunit, ribosome biogenesis, GCN4, dietary restriction, caloric restriction, aging, nutrient signaling, TOR kinase, protein kinase A, epistasis analysis, Saccharomyces cerevisiae
- MeSH terms
- DNA-Binding Proteins, Histone Deacetylases, Ribosomal Proteins, Saccharomyces cerevisiae, Transcription Factors, Gene Deletion, Saccharomyces cerevisiae Proteins, Sirtuins, Silent Information Regulator Proteins, Saccharomyces cerevisiae, Basic-Leucine Zipper Transcription Factors, Ribosome Subunits, Large, Eukaryotic, Sirtuin 2
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