CAREER: Effects of mitohormesis on reproduction and longevity

Auburn University, Auburn AL

Investigators

Abstract

A central tenet of biology is that allocation to reproduction trades off against allocation to processes that enhance longevity. Reproduction takes energy and energy production induces the release of damaging reactive oxygen species (ROS) within the mitochondria. ROS are normal byproducts of cellular respiration that can damage cells and as a result, reduce longevity. Yet, several studies have now shown that damage from ROS is typically unchanged or even reduced in animals that reproduce compared to those that don't. In addition, new theory suggests that low levels of exposure to ROS, as occurs during reproduction, not only lowers damage from ROS but may also protect cells from the cellular damage that contributes to aging. The goals of this project are to test if the ROS generated during reproduction protects against future ROS damage, determine how ROS damage and the performance of mitochondria change with reproductive experience and age, and characterize the relationship between reproductive experience and longevity in the house mouse. Research on the interaction between mitochondrial function, reproduction, and longevity will be used as a platform for education and the improvement of science literacy in the state of Alabama. In collaboration of with local biology teachers, lesson plans with labs will be developed for 7th and 9th graders. These lessons will feature the proposed research on mitochondria and aging and will be submitted to the Alabama State Board of Education for adoption in every 7th and 9th grade biology classroom in Alabama. In addition, Auburn graduate students will be challenged to commit to regular participation in outreach in a graduate-level seminar "mitochondria and energetics". Students will prepare and present a lesson for Auburn University's Get Under the Surface program that invites 5th grade students and their parents to campus to participate in an interactive laboratory. The goals of this CAREER project are to 1) test whether reproduction protects against future oxidative damage and 2) to determine if mitochondrial function and the cellular response to an induced oxidative stressor change with age in a continuously breeding species, the house mouse (Mus musculus). Given the potentially protective effects that reproduction has on processes that induce aging, a third goal of this project is 3) to evaluate the interaction between reproduction and longevity in female mice by comparing age at death in females that have bred few times verses those that have bred many times. Several cutting-edge techniques will be employed in this investigation including measurements of ROS production from mitochondria and oxidative damage in organs that commonly decline during senescence. In addition, respiratory control ratio, electron chain complex activity, mitochondrial biogenesis, abundance of uncoupling proteins and levels of endogenous antioxidants will be evaluated. The impact of treatment on insulin-like growth factor-1 and telomere length will also be evaluated as indicators of the impact of treatment on aging. This investigation will provide a detailed assessment of the role that reproduction plays in the accumulation of ROS and in resistance to stressors that hasten aging. Unlike many studies that have searched for a mechanistic basis for the tradeoff between reproduction and longevity, this study will ask whether such a tradeoff really exists. Whether this study supports or refutes the idea that ROS produced during reproduction contributes to age, the project will transform the study of life-history evolution, and the outcome will be a better understanding of the mechanistic relationship between aging and reproduction.