Evolutionary biologists have been interested in the negative interactions among life history traits for nearly a century, but the mechanisms that would create this negative interaction remain poorly understood. One variable that has emerged as a likely link between reproductive effort and longevity is oxidative stress. Specifically, it has been proposed that reproduction generates free radicals that cause oxidative stress and, in turn, oxidative stress damages cellular components and accelerates senescence. We propose that there is limited support for the hypothesis because reactive oxygen species (ROS), the free radicals implicated in oxidative damage, are not consistently harmful. With this review, we define the hormetic response of mitochondria to ROS, termed mitochondrial hormesis, and describe how to test for a mitohormetic response. We interpret existing data using our model and propose that experimental manipulations will further improve our knowledge of this response. Finally, we postulate how the mitohormetic response curve applies to variation in animal performance and longevity.

Energy allocation theory predicts that a lactating female should alter the energetic demands of its organ systems in a manner that maximizes nutrient allocation to reproduction while reducing nutrient use for tasks that are not vital to immediate survival. We posit that organ‐specific plasticity in the function of mitochondria plays a key role in mediating these energetic trade‐offs. The goal of this project was to evaluate mitochondrial changes that occur in response to lactation in two of the most energetically demanding organs in the body of a rodent, the liver and skeletal muscle. This work was conducted in wild‐derived house mice (Mus musculus) kept in seminatural enclosures that allow the mice to maintain a natural social structure and move within a home range size typical of wild mice. Tissues were collected from females at peak lactation and from age‐matched nonreproductive females. Mitochondrial respiration, oxidative damage, antioxidant, PGC‐1α, and uncoupling protein levels were compared between lactating and nonreproductive females. Our findings suggest that both liver and skeletal muscle downregulate specific antioxidant proteins during lactation. The liver, but not skeletal muscle, of lactating females displayed higher oxidative damage than nonreproductive females. The liver mass of lactating females increased, but the liver displayed no change in mitochondrial respiratory control ratio. Skeletal muscle mass and mitochondrial respiratory control ratio were not different between groups. However, the respiratory function of skeletal muscle did vary among lactating females as a function of stage of concurrent pregnancy, litter size, and mass of the mammary glands. The observed changes are predicted to increase the efficiency of skeletal muscle mitochondria, reducing the substrate demands of skeletal muscle during lactation. Differences between our results and prior studies highlight the role that an animals’ social and physical environment could play in how it adapts to the energetic demands of reproduction.

Reproduction is thought to come at a cost to longevity. Based on the assumption that increased energy expenditure during reproduction is associated with increased free-radical production by mitochondria, oxidative damage has been suggested to drive this trade-off. We examined the impact of reproduction on liver mitochondrial function by utilizing post-reproductive and non-reproductive house mice (Mus musculus) living under semi-natural conditions. The age-matched post-reproductive and non-reproductive groups were compared after the reproductive females returned to a non-reproductive state, so that both groups were in the same physiological state at the time the liver was collected. Despite increased oxidative damage (p = 0.05) and elevated CuZnSOD (p = 0.002) and catalase (p = 0.04) protein levels, reproduction had no negative impacts on the respiratory function of liver mitochondria. Specifically, in a post-reproductive, maintenance state the mitochondrial coupling (i.e., respiratory control ratio) of mouse livers show no negative impacts of reproduction. In fact, there was a trend (p = 0.059) to suggest increased maximal oxygen consumption by liver mitochondria during the ADP stimulated state (i.e., state 3) in post-reproduction. These findings suggest that oxidative damage may not impair mitochondrial respiratory function and question the role of mitochondria in the trade-off between reproduction and longevity. In addition, the findings highlight the importance of quantifying the respiratory function of mitochondria in addition to measuring oxidative damage.