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Co-chaperone p23 regulates C. elegans Lifespan in Response to Temperature
Makoto Horikawa1, Surojit Sural2, Ao-Lin Hsu3
1Max Planck Institute for Biology of Ageing, Cologne, Germany.
Plos Genetics
|April 2, 2015
Summary
The C. elegans daf-41 gene regulates lifespan and dauer diapause entry in response to temperature. This gene impacts longevity by modulating key transcriptional changes in longevity pathways, affecting heat shock and insulin signaling.
Area of Science:
- Genetics
- Molecular Biology
- Aging Research
Background:
- Temperature significantly influences physiological processes, including aging and lifespan, particularly in ectotherms.
- While thermal effects on lifespan are often linked to metabolic rate, evidence suggests regulated processes are also involved.
- The C. elegans daf-41 gene, a homolog of p23 co-chaperone/prostaglandin E synthase-3, is implicated in temperature-dependent physiological regulation.
Purpose of the Study:
- To investigate the role of the C. elegans daf-41 gene in temperature-mediated lifespan regulation and dauer diapause.
- To elucidate the molecular mechanisms by which daf-41 influences longevity pathways in response to thermal stress.
- To determine the genetic pathways and signaling molecules interacting with daf-41 in temperature-dependent aging.
Main Methods:
- Utilized C. elegans as a model organism to study gene function and lifespan.
- Generated daf-41 deletion mutants and analyzed their phenotypes at different temperatures.
- Employed genetic analysis, including studying interactions with daf-10, daf-16/FOXO, and daf-12/FXR.
- Assessed gene expression of DAF-16 and HSF-1 targets and analyzed heat shock response element occupancy.
Main Results:
- daf-41 deletion triggers constitutive dauer diapause at elevated temperatures, dependent on neurosensory, insulin/IGF-1, and steroidal signaling pathways.
- daf-41 mutants exhibit altered temperature-dependent longevity: longer lifespan at 25°C and shorter lifespan at 15°C compared to wild-type.
- Longevity at 25°C involves daf-16/FOXO and heat shock factor hsf-1, while short lifespan at 15°C involves daf-16/FOXO and daf-12/FXR.
- daf-41 affects the expression of DAF-16 and HSF-1 target genes and increases heat shock response element occupancy at high temperatures.
Conclusions:
- The daf-41 gene plays a critical role in governing entry into dauer diapause and regulating adult lifespan in response to temperature.
- daf-41 acts as a key regulator, modulating transcriptional changes in longevity pathways, including those involving DAF-16/FOXO and HSF-1.
- These findings reveal a complex, regulated mechanism by which temperature influences aging and lifespan through the daf-41 co-chaperone.

