Extension of Chronological Life Span in Yeast by Decreased TOR Pathway Signaling
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Chronological life span (CLS) in Saccharomyces cerevisiae, defined as the time cells in a stationary phase culture remain viable, has been proposed as a model for the aging of post-mitotic tissues in mammals. We developed a high-throughput assay to determine CLS for approximately 4800 single-gene deletion strains of yeast, and identified long-lived strains carrying mutations in the conserved TOR pathway. TOR signaling regulates multiple cellular processes in response to nutrients, especially amino acids, raising the possibility that decreased TOR signaling mediates life span extension by calorie restriction. In support of this possibility, removal of either asparagine or glutamate from the media significantly increased stationary phase survival. Pharmacological inhibition of TOR signaling by methionine sulfoximine or rapamycin also increased CLS. Decreased TOR activity also promoted increased accumulation of storage carbohydrates and enhanced stress resistance and nuclear relocalization of the stress-related transcription factor Msn2. We propose that up-regulation of a highly conserved response to starvation-induced stress is important for life span extension by decreased TOR signaling in yeast and higher eukaryotes.
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Metformin, like rapamycin, is known to inhibit mTOR signaling.
“Of significance is that metformin, like rapamycin, is known to inhibit mTOR signaling, and the inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster (fruit fly) (221–225).”
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Inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster.
“Of significance is that metformin, like rapamycin, is known to inhibit mTOR signaling, and the inhibition of the mTOR signaling pathway with rapamycin has been shown to extend lifespan in C. elegans, S. cerevisiae, and Drosophila melanogaster (fruit fly) (221–225).”
From A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan (2021) · cites this paper as [221]
Ras/PKA and TOR/Sch9 signaling pathways promote translation and growth and suppress longevity in response to nutrients.
“In addition, the Ras/PKA and TOR/Sch9 signaling pathways were found to promote translation and growth and suppress longevity in response to nutrients (Powers et al., 2006).”
From Programmed cell death in aging (2015) · cites this paper as Powers et al., 2006
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- Authors
- Powers, R. W., Kaeberlein, M., Caldwell, S. D., Kennedy, B. K., & Fields, S.
- Affiliations
- Howard Hughes Medical Institute (US)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2006-01-15
- Volume
- 20
- Issue
- 2
- Pages
- 174-184
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1356109
- OpenAlex
- W2138138136
- Cited by
- 982
- References
- 86
- Citations by year
- 2026: 25 · 2025: 28 · 2024: 35 · 2023: 41 · 2022: 35 · 2021: 44 · 2020: 39 · 2019: 53 · 2018: 52 · 2017: 51 · 2016: 50 · 2015: 73 · 2014: 51 · 2013: 73 · 2012: 53
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- University of Washington
- National Institutes of Health (AG013280)
- National Institute on Aging (P30AG013280)
- 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
- chronological lifespan, TOR signaling, Saccharomyces cerevisiae, aging, caloric restriction, amino acid starvation, asparagine, glutamate, methionine sulfoximine, rapamycin, storage carbohydrates, stress tolerance, Msn2, stationary phase survival
- MeSH terms
- Amino Acids, DNA-Binding Proteins, Hot Temperature, Longevity, Mutation, Phenotype, Repressor Proteins, Saccharomyces cerevisiae, Transcription Factors, Signal Transduction, Gene Expression Regulation, Fungal, Conserved Sequence, Protein Serine-Threonine Kinases, Gene Deletion, Sequence Homology, Oxidative Stress, Nuclear Localization Signals, Saccharomyces cerevisiae Proteins
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