Disruption of insulin signalling preserves bioenergetic competence of mitochondria in ageing Caenorhabditis elegans
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Background: The gene daf-2 encodes the single insulin/insulin growth factor-1-like receptor of Caenorhabditis elegans. The reduction-of-function allele e1370 induces several metabolic alterations and doubles lifespan. Results: We found that the e1370 mutation alters aerobic energy production substantially. In wild-type worms the abundance of key mitochondrial proteins declines with age, accompanied by a dramatic decrease in energy production, although the mitochondrial mass, inferred from the mitochondrial DNA copy number, remains unaltered. In contrast, the age-dependent decrease of both key mitochondrial proteins and bioenergetic competence is considerably attenuated in daf-2(e1370) adult animals. The increase in daf-2(e1370) mitochondrial competence is associated with a higher membrane potential and increased reactive oxygen species production, but with little damage to mitochondrial protein or DNA. Together these results point to a higher energetic efficiency of daf-2(e1370) animals. Conclusions: We conclude that low daf-2 function alters the overall rate of ageing by a yet unidentified mechanism with an indirect protective effect on mitochondrial function.
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The increased respiratory capacity in DAF-2 mutants, unlike adult wild-type N2 worms, agrees with findings of increased mitochondrial ROS production.
“The detected increase in respiratory capacity in DAF-2 mutants, contrary to what was observed in adult wild-type N2 worms, is in agreement with findings showing increased mitochondrial ROS production19.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [19]
The increase in ROS production in DAF-2 mutants occurred without detectable adverse effects on mtDNA integrity or oxidative protein damage.
“Importantly, this increase in ROS production was observed without any detectable adverse effect in mtDNA integrity and oxidative protein damage19.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [19]
DAF-2 mutants have increased OXPHOS protein abundance, respiratory capacity, and membrane potential.
“Moreover, DAF-2 mutants have increased abundance of proteins involved in OXPHOS, increased respiratory capacity and increased membrane potential19.”
From Mitochondrial and metabolic dysfunction in ageing and age-related diseases (2022) · cites this paper as [19]
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- Authors
- Brys, K., Castelein, N., Matthijssens, F., Vanfleteren, J. R., & Braeckman, B. P.
- Affiliations
- Ghent University (BE)
- Corresponding author
- Braeckman, Bart P
- Venue
- BMC Biology
- Published
- 2010-06-28
- Volume
- 8
- Issue
- 1
- Pages
- 91-91
- ISSN
- 1741-7007 (ISSN-L)
- PMC
- PMC2914644
- OpenAlex
- W2028298077
- Cited by
- 74
- References
- 69
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 5 · 2018: 7 · 2017: 4 · 2016: 8 · 2015: 2 · 2014: 8 · 2013: 5 · 2012: 6
- FWCI
- 1.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by
- Locations
- BMC Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion, other-oa)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Universiteit Gent
- Vlaamse regering
- National Institutes of Health
- 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 › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- insulin signaling, daf-2, Caenorhabditis elegans, aging, mitochondrial function, bioenergetics, lifespan extension, mitochondrial proteins, mitochondrial DNA copy number, mitochondrial membrane potential, reactive oxygen species
- MeSH terms
- Aging, Alleles, Animals, Hydrogen Peroxide, Insulin, Mitochondria, Mutation, Receptor, Insulin, Caenorhabditis elegans, Oxidative Stress, Caenorhabditis elegans Proteins
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