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Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients
Abstract
Calorie restriction increases life span in many organisms, including the budding yeast Saccharomyces cerevisiae . From a large-scale analysis of 564 single-gene–deletion strains of yeast, we identified 10 gene deletions that increase replicative life span. Six of these correspond to genes encoding components of the nutrient-responsive TOR and Sch9 pathways. Calorie restriction of tor1 D or sch9 D cells failed to further increase life span and, like calorie restriction, deletion of either SCH9 or TOR1 increased life span independent of the Sir2 histone deacetylase. We propose that the TOR and Sch9 kinases define a primary conduit through which excess nutrient intake limits longevity in yeast.
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“Inhibition of the TOR signalling pathway by genetic or pharmacological intervention extends lifespan in invertebrates, including yeast, nematodes and fruit flies1–5.”
From Rapamycin fed late in life extends lifespan in genetically heterogeneous mice (2009) · cites this paper as [1]
In the citing paper
“Initial evidence that reduced TOR function can extend longevity came primarily from studies in yeast1,2 and invertebrates3–5.”
From Rapamycin fed late in life extends lifespan in genetically heterogeneous mice (2009) · cites this paper as [1]
In the citing paper
“Studies in yeast, worms and flies found that genetic inhibition of mTORC1 or signaling pathways downstream of mTORC1, including S6K and translation initiation factors, extends lifespan 5–11.”
From Targeting the biology of aging with mTOR inhibitors (2023) · cites this paper as [5]
In the citing paper
“Animal models exploring the effect of rapamycin and rapalogs on longevity have determined their ability to extend lifespan167-169.”
From SARS-CoV-2, COVID-19 and the aging immune system (2021) · cites this paper as [167]
In the citing paper
“Of significance, TOR inactivation extends lifespan in yeast (Kaeberlein et al., 2005), flies (Kapahi et al., 2004), worms (Vellai et al., 2003) and mice (Harrison et al., 2009).”
From The Search for Antiaging Interventions: From Elixirs to Fasting Regimens (2014) · cites this paper as Kaeberlein et al., 2005
In the citing paper
“In many organisms, decreased TOR signalling is associated with the extension of life span 87, 88, 89 .”
From The common biology of cancer and ageing (2007) · cites this paper as [89]
In the citing paper
“Similarly, under some conditions, TOR signalling seems to be required for the longevity benefits of caloric restriction in yeast 89 .”
From The common biology of cancer and ageing (2007) · cites this paper as [89]
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Metadata
- Authors
- Kaeberlein, M., Powers, R. W., Steffen, K. K., Westman, E. A., Hu, D., Dang, N., Kerr, E. O., Kirkland, K. T., Fields, S., & Kennedy, B. K.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Kaeberlein, Matt
- Kennedy, Brian K.
- Venue
- Science
- Published
- 2005-11-18
- Volume
- 310
- Issue
- 5751
- Pages
- 1193-1196
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2077612844
- Cited by
- 1,293
- References
- 24
- Citations by year
- 2026: 21 · 2025: 30 · 2024: 33 · 2023: 47 · 2022: 46 · 2021: 53 · 2020: 57 · 2019: 64 · 2018: 58 · 2017: 53 · 2016: 76 · 2015: 81 · 2014: 91 · 2013: 75 · 2012: 88
- FWCI
- 16.70
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- Funders
- 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 › Geriatrics and Gerontology › Sirtuins and Resveratrol in Medicine
- Keywords
- replicative lifespan, TOR signaling, caloric restriction, nutrient signaling, longevity, Saccharomyces cerevisiae, TOR1, Sch9
- MeSH terms
- Cell Division, Protein Kinases, Saccharomyces cerevisiae, Protein Serine-Threonine Kinases, Gene Deletion, Saccharomyces cerevisiae Proteins
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