How telomere dynamics are influenced by the balance between mitochondrial efficiency, reactive oxygen species production and DNA damage.

Abstract

It is well known that oxidative stress is a major cause of DNA damage and telomere attrition. Most endogenous reactive oxygen species (ROS) are produced in the mitochondria, producing a link between mitochondrial function, DNA integrity and telomere dynamics. In this review we will describe how ROS production, rates of damage to telomeric DNA and DNA repair are dynamic processes. The rate of ROS production depends on mitochondrial features such as the level of inner membrane uncoupling and the proportion of time that ATP is actively being produced. However, the efficiency of ATP production (the ATP/O ratio) is positively related to the rate of ROS production, so leading to a trade-off between the body's energy requirements and its need to prevent oxidative stress. Telomeric DNA is especially vulnerable to oxidative damage due to features such as its high guanine content; while repair to damaged telomere regions is possible through a range of mechanisms, these can result in more rapid telomere shortening. There is increasing evidence that mitochondrial efficiency varies over time and with environmental context, as do rates of DNA repair. We argue that telomere dynamics can only be understood by appreciating that the optimal solution to the trade-off between energetic efficiency and telomere protection will differ between individuals and will change over time, depending on resource availability, energetic demands and life history strategy.