Evolutionary conservation of the clk-1 -dependent mechanism of longevity: loss of mclk1 increases cellular fitness and lifespan in mice
Open accessAbstract
Inactivation of the Caenorhabditis elegans gene clk-1 , which is required for ubiquinone biosynthesis, increases lifespan by an insulin signaling-independent mechanism. We find that homozygous inactivation of mclk1 , the mouse ortholog of clk-1 , yields ES cells that are protected from oxidative stress and damage to DNA. Moreover, in the livers of old mclk1 +/- mice, hepatocytes that have lost mclk1 expression by loss of heterozygosity undergo clonal expansion, suggesting that their resistance to stress allows them to outcompete cells that still express the gene. mclk1 +/- mice, whose growth and fertility are normal, also display a substantial increase in lifespan in each of three different genetic backgrounds. These observations indicate that the distinct mechanism by which clk-1/mclk1 affects lifespan is evolutionarily conserved from nematodes to mammals and is not tied to a particular anatomy or physiology.
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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 [40]
Mice heterozygous for mitochondrial glutathione peroxidase 4 or the ubiquinone biosynthesis protein CLK1 display high levels of mitochondrial oxidative stress, yet live longer than their wild-type counterparts.
“Mice heterozygous for the mitochondrial glutathione peroxidase 4 or the ubiquinone biosynthesis protein CLK1 display high levels of mitochondrial oxidative stress, yet live longer than their wild-type counterparts 93, 94.”
From Mitochondrial reactive oxygen species regulate cellular signaling and dictate biological outcomes (2010) · cites this paper as [94]
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References 51 · Cited by 345
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- Dean, F.B., Hosono, S., Fang, L., Wu, X., Faruqi, A.F., Bray-Ward, P., Sun, Z., Zong, Q., Du, Y., Du, J., et al. 2002. Comprehen- sive human genome amplification using multiple displace- ment amplification. Proc. Natl. Acad. Sci. 99: 5261-5266.
- Authors
- Liu, X., Jiang, N., Hughes, B., Bigras, E., Shoubridge, E., & Hekimi, S.
- Affiliations
- McGill University (CA)
- Montreal Neurological Institute and Hospital (CA)
- Venue
- Genes & Development
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2005-09-29
- Volume
- 19
- Issue
- 20
- Pages
- 2424-2434
- ISSN
- 0890-9369 (ISSN-L)
- 1549-5477
- PMC
- PMC1257397
- OpenAlex
- W2142353558
- Cited by
- 345
- References
- 51
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 16 · 2023: 13 · 2022: 17 · 2021: 15 · 2020: 16 · 2019: 17 · 2018: 27 · 2017: 16 · 2016: 22 · 2015: 17 · 2014: 28 · 2013: 9 · 2012: 11
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes & Development (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- HighWire Press Open Archive (submittedVersion)
- Funders
- Howard Hughes Medical Institute
- Canadian Institutes of Health Research
- 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 › Coenzyme Q10 studies and effects
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- clk-1, ubiquinone biosynthesis, lifespan extension, longevity, oxidative stress resistance, DNA damage resistance, clonal expansion, loss of heterozygosity, hepatocytes, embryonic stem cells, evolutionary conservation, Caenorhabditis elegans, mice
- MeSH terms
- Animals, Crosses, Genetic, DNA Damage, Embryo, Mammalian, Embryo, Nonmammalian, Mixed Function Oxygenases, Longevity, Membrane Proteins, Stem Cells, Ubiquinone, Caenorhabditis elegans, Mice, Knockout, Oxidative Stress, Evolution, Molecular, Loss of Heterozygosity, Hepatocytes, Mitochondrial Proteins, Caenorhabditis elegans Proteins, Mice
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