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A Regulated Response to Impaired Respiration Slows Behavioral Rates and Increases Lifespan in Caenorhabditis elegans
Open accessAbstract
When mitochondrial respiration or ubiquinone production is inhibited in Caenorhabditis elegans, behavioral rates are slowed and lifespan is extended. Here, we show that these perturbations increase the expression of cell-protective and metabolic genes and the abundance of mitochondrial DNA. This response is similar to the response triggered by inhibiting respiration in yeast and mammalian cells, termed the "retrograde response". As in yeast, genes switched on in C. elegans mitochondrial mutants extend lifespan, suggesting an underlying evolutionary conservation of mechanism. Inhibition of fstr-1, a potential signaling gene that is up-regulated in clk-1 (ubiquinone-defective) mutants, and its close homolog fstr-2 prevents the expression of many retrograde-response genes and accelerates clk-1 behavioral and aging rates. Thus, clk-1 mutants live in "slow motion" because of a fstr-1/2-dependent pathway that responds to ubiquinone. Loss of fstr-1/2 does not suppress the phenotypes of all long-lived mitochondrial mutants. Thus, although different mitochondrial perturbations activate similar transcriptional and physiological responses, they do so in different ways.
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“Unexpectedly, reduced mitochondrial function can, in some circumstances, increase lifespan.”
From Neural mechanisms of ageing and cognitive decline (2010) · cites this paper as [38]
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Metadata
- Authors
- Cristina, D., Cary, M., Lunceford, A., Clarke, C., & Kenyon, C.
- Affiliations
- University of California, San Francisco (US)
- University of California, Los Angeles (US)
- Corresponding author
- Kenyon, Cynthia
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-04-10
- Volume
- 5
- Issue
- 4
- Pages
- e1000450
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC2660839
- OpenAlex
- W2086324577
- Cited by
- 166
- References
- 41
- Citations by year
- 2026: 8 · 2025: 5 · 2024: 3 · 2023: 2 · 2022: 10 · 2021: 6 · 2020: 15 · 2019: 10 · 2018: 8 · 2017: 6 · 2016: 10 · 2015: 11 · 2014: 21 · 2013: 5 · 2012: 12
- FWCI
- 4.71
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS Genetics (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- eScholarship (California Digital Library) (submittedVersion, cc-by)
- Figshare (submittedVersion, cc-by)
- Funders
- Genome Canada
- Genome British Columbia
- National Institutes of Health
- University of California, San Francisco
- National Center for Research Resources
- 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 › Cell Biology › Autophagy in Disease and Therapy
- Keywords
- mitochondrial respiration inhibition, coenzyme Q10, clk-1, retrograde response, lifespan extension, aging, Caenorhabditis elegans, mitochondrial mutants, gene expression response
- MeSH terms
- Animals, Behavior, Animal, Gene Expression Regulation, Longevity, Mitochondria, Mutation, Caenorhabditis elegans, Cell Respiration, Models, Animal, Caenorhabditis elegans Proteins
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