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Updated: Apr 18, 2026
Surveying Low-Cost Methods to Measure Lifespan and Healthspan in Caenorhabditis elegans
Published on: May 18, 2022
PCH-2 regulates Caenorhabditis elegans lifespan
Hong Qian1, Xiangru Xu1, Laura E Niklason1,2
1Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.
Abstract:
Components or downstream targets of many signaling pathways such as Insulin/IGF-1 and TOR, as well as genes involved in cellular metabolism and bioenergetics can extend worm lifespan 20% or more. The C. elegans gene pch-2 and its homologs, including TRIP13 in humans, have been studied for their functions in cell mitosis and meiosis, but have never been implicated in lifespan regulation. Here we show that over-expression of TRIP13 in human fibroblasts confers resistance to environmental stressors such as UV radiation and oxidative stress. Furthermore, pch-2 overexpression in C. elegans extends worm lifespan, and enhances worm survival in response to various stressors. Conversely, reducing pch-2 expression with RNAi shortens worm lifespan. Additional genetic epistasis analysis indicates that the molecular mechanism of pch-2 in worm longevity is tied to functions of the sirtuin family, implying that pch-2 is another chromatin regulator for worm longevity. These findings suggest a novel function of the pch-2 gene involved in lifespan determination.
Insights
Overexpressing the TRIP13 gene in humans and the pch-2 gene in worms enhances stress resistance and extends lifespan. This suggests a novel role for pch-2 in longevity regulation, linked to sirtuin family functions.
Area of Science:
- Genetics
- Aging Research
- Cell Biology
Background:
- Insulin/IGF-1 and TOR pathways, along with metabolic genes, are known lifespan regulators in C. elegans.
- The TRIP13 gene and its C. elegans homolog pch-2 are primarily studied for roles in cell division (mitosis and meiosis).
- No prior studies have linked pch-2 or TRIP13 to lifespan regulation.
Purpose of the Study:
- To investigate the potential role of pch-2/TRIP13 in lifespan determination and stress resistance.
- To elucidate the molecular mechanisms underlying pch-2's function in longevity.
Main Methods:
- Overexpression of TRIP13 in human fibroblasts.
- Overexpression and RNA interference (RNAi) of pch-2 in C. elegans.
- Assessing stress resistance (UV, oxidative stress) in human cells and worms.
- Genetic epistasis analysis in C. elegans.
Main Results:
- TRIP13 overexpression confers resistance to UV and oxidative stress in human fibroblasts.
- pch-2 overexpression extends C. elegans lifespan and enhances survival under stress.
- Reducing pch-2 expression via RNAi shortens worm lifespan.
- Epistasis analysis reveals pch-2's longevity mechanism involves the sirtuin family.
Conclusions:
- The pch-2 gene plays a novel role in regulating lifespan and stress resistance in C. elegans.
- pch-2 functions as a chromatin regulator in longevity pathways, potentially through sirtuin interactions.
- TRIP13 may represent a conserved target for interventions aimed at enhancing stress resilience and longevity.
