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Research Paper|Volume 7, Issue 1|pp 1—13

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
  • 2Department of Biomedical Engineering, Yale University, New Haven, CT 06520, USA
Received: December 11, 2014Accepted: December 28, 2014Published: January 15, 2015
https://doi.org/10.18632/aging.100713

Copyright: © 2015 Qian et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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