Cited by 166Genetics, Aging, and Longevity in Model OrganismsMitochondrial Function and PathologyAutophagy in Disease and Therapy

A Regulated Response to Impaired Respiration Slows Behavioral Rates and Increases Lifespan in Caenorhabditis elegans

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Cristina, David, Cary, Michael, Lunceford, Adam, Clarke, Catherine, Kenyon, Cynthia·2009·PLoS Genetics

Abstract

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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  • Reduced mitochondrial function can, in some circumstances, increase lifespan.

    “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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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
Published
2009-04-10
Volume
5
Issue
4
Pages
e1000450
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
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
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
  • Health Sciences › Medicine › Epidemiology › 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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