Cited by 422Genetics, Aging, and Longevity in Model OrganismsMitochondrial Function and PathologyFungal and yeast genetics research

Reduced TOR Signaling Extends Chronological Life Span via Increased Respiration and Upregulation of Mitochondrial Gene Expression

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Bonawitz, Nicholas D., Chatenay-Lapointe, Marc, Pan, Yong, Shadel, Gerald S.·2007·Cell Metabolism

Abstract

The relationships between mitochondrial respiration, reactive oxygen species (ROS), and life span are complex and remain controversial. Inhibition of the target of rapamycin (TOR) signaling pathway extends life span in several model organisms. We show here that deletion of the TOR1 gene extends chronological life span in Saccharomyces cerevisiae, primarily by increasing mitochondrial respiration via enhanced translation of mtDNA-encoded oxidative phosphorylation complex subunits. Unlike previously reported pathways regulating chronological life span, we demonstrate that deletion of TOR1 delays aging independently of the antioxidant gene SOD2. Furthermore, wild-type and tor1 null strains differ in life span only when respiration competent and grown in normoxia in the presence of glucose. We propose that inhibition of TOR signaling causes derepression of respiration during growth in glucose and that the subsequent increase in mitochondrial oxygen consumption limits intracellular oxygen and ROS-mediated damage during glycolytic growth, leading to lower cellular ROS and extension of chronological life span.

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Crossref · 10.1016/j.cmet.2007.02.009

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  • Nutrient sensing and energy homeostasis have been implicated as connecting mitochondrial function and longevity.

    “Nutrient sensing and energy homeostasis have been implicated as connecting mitochondrial function and longevity104,105.”

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Authors
Bonawitz, N. D., Chatenay-Lapointe, M., Pan, Y., & Shadel, G. S.
Affiliations
  • Emory University (US)
  • Yale University (US)
Corresponding author
Shadel, Gerald S.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2007-04
Volume
5
Issue
4
Pages
265-277
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2064638523
Cited by
422
References
50
Citations by year
2026: 12 · 2025: 3 · 2024: 11 · 2023: 17 · 2022: 13 · 2021: 10 · 2020: 13 · 2019: 17 · 2018: 19 · 2017: 21 · 2016: 23 · 2015: 32 · 2014: 31 · 2013: 26 · 2012: 26
FWCI
9.78
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health
  • National Institute of General Medical Sciences (T32GM007499, 5 T32 GM07499-30)
  • Army Research Office
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 › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
Keywords
TOR signaling, chronological lifespan, aging, mitochondrial respiration, oxidative phosphorylation, mitochondrial gene expression, reactive oxygen species, manganese superoxide dismutase, glucose metabolism, Saccharomyces cerevisiae, oxygen consumption
MeSH terms
Superoxide Dismutase 2, Glucose, Longevity, Mitochondria, Models, Biological, Oxygen Consumption, Saccharomyces cerevisiae, Superoxide Dismutase, Protein Biosynthesis, Signal Transduction, Gene Expression Regulation, Fungal, Gene Deletion, Phosphotransferases (Alcohol Group Acceptor), Cell Respiration, Phosphatidylinositol 3-Kinases, Saccharomyces cerevisiae Proteins, Organisms, Genetically Modified

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