The effects of spontaneous mutations on lifespan and oxidative stress in the nematodes Caenorhabditis elegans and C briggsae


Meeting Abstract

P2.25  Friday, Jan. 4  The effects of spontaneous mutations on lifespan and oxidative stress in the nematodes Caenorhabditis elegans and C. briggsae JOYNER-MATOS, J.L.*; UPADHYAY, A.; LEEUWENBURGH, C.; BAER, C.F.; Univ. of Florida, Gainesville jjmatos@ufl.edu

Why individual organisms age is a longstanding unresolved question. Hypotheses for the evolution of aging invoke the effects of deleterious mutations and the fact that the strength of natural selection decreases with organism age. Mechanistic hypotheses address cellular-level changes including increased free radical (ROS) production and resulting oxidative damage and mutation accumulation in aging tissues. We examined the effects of spontaneous mutations on lifespan and ROS metabolism in two nematode species, Caenorhabditis elegans and C. briggsae. Initially isogenic populations accumulated mutations in the (relative) absence of natural selection for 250 generations, which resulted in a significant decline in mean fitness and increase in variance in fitness in comparison to ancestral controls. Mean lifespan of MA lines of each species averaged one day (~6%) shorter than that of ancestral controls. To examine the link between ROS, mutation and lifespan, we assessed steady-state levels of RNA oxidative damage and survivorship on paraquat, which generates ROS. RNA oxidation, the number of oxidized bases (8-oxoGuo) per 106 guanosine bases, was significantly higher in C. elegans MA lines than in ancestral controls (p ≤ 0.003). Paraquat exposure severely slowed development and survival to adulthood of MA and control lines of both species (p ≤ 0.0001). In general, more worms from ancestral control lines exposed to paraquat developed to the second or third (of four) larval stages than did worms from MA lines (C. briggsae, p ≤ 0.05). These results suggest that mutation accumulation has a detrimental effect on nematode lifespan, possibly by decreasing their ability to minimize oxidative damage or withstand an exogenous oxidative stress.

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