Title

Defining the Mechanisms Underlying Extended Longevity in C. elegans Mitochondrial Mutants

Student Author(s)

Claire Schaar

Faculty Mentor(s)

Dr. Jeremy Van Raamsdonk

Document Type

Poster

Event Date

4-10-2015

Abstract

Mutations affecting the function of the mitochondrial electron transport chain result in a long-lived phenotype in Caenorhabditis elegans. Recent work has shown that these mutations result in increased levels of reactive oxygen species (ROS). As it was previously thought that damage caused by high levels of ROS leads to aging, it is surprising that these mitochondrial mutants exhibit higher levels of ROS and an increased lifespan. Subsequent studies have shown that the higher levels of ROS in the longlived mitochondrial mutants actually contribute to their increased lifespan. In this study, we sought to determine how the upregulation of stress response pathways and alterations in metabolism contribute to the longevity of three mitochondrial mutants:: clk-1, isp-1, and nuo-6. Using fluorescent reporters to visualize the activation of stress response pathways throughout the lifespan of the worm, we found that the mitochondrial unfolded protein response and the oxidative stress response are upregulated in all three mutants, while the antioxidant defense pathway is most upregulated in isp-1 worms. Since mutations to the electron chain likely lead to a deficiency in energy production, it has been hypothesized that mitochondrial mutants may shift toward using glycolysis as a larger source of energy and that this shift in metabolism may contribute to their longevity. We examined the effect of using RNAi to knockdown the expression of aldo-1, a gene necessary for glycolysis, on the longevity of the three mitochondrial mutants. We found that aldo-1 is required for the long lifespan of isp-1 and nuo-6 mutants but not clk-1. Overall, this work has provided additional insights into the roles of stress response pathways and metabolism in mitochondrial mutant longevity.

Comments

This research was supported by the Frederick and Lena Meijer Student Internship Program.

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