|dc.description.abstract||Energy investment in reproduction comes at the cost of other life history traits, including future reproductive output and ultimately, lifespan. The disposable soma theory suggests that there is a negative relationship between reproduction and longevity, proposing that allocation of energy to reproduction compromises the availability of energy for tissue repair and maintenance and, therefore, reduces longevity. However, the mechanism behind this tradeoff is fully not understood. Recently, investigation has focused on the negative byproducts of respiration, free radicals, and mitochondria as the source of the cost that reproduction exacts on self-maintenance and longevity. Herein, I investigate the changes to mitochondrial efficiency and cell redox state of skeletal muscle and liver of house mice at peak-lactation, as well as measure the effects of reproduction on mitochondrial function in a post-reproductive, maintenance state in the house mouse.
Life history theory predicts that during reproduction, energy will be allocated more heavily to tissues that support reproduction than to those that primarily support maintenance efforts. In chapter 1, I examined the plasticity of mitochondrial function in the liver and skeletal muscle during reproduction to determine if organs adopt different strategies for sparing substrate for the high-energy demand of supporting offspring growth. In addition, I asked if these changes were likely to expose the organ to damage that could impact the ability of the organ to maintain itself. Reproductive female house mice were collected at peak-lactation of their third successful litter and mitochondrial function of their tissues was compared to non-reproductive individuals. Skeletal muscle maintained mitochondrial functionality during lactation with a more coupled basal metabolism. These changes were coupled with lower antioxidant production and lower mitochondrial subunit expression, both of which are substrate-sparing changes, potentially sparing nutrients to support milk synthesis. However, at peak-lactation there is evidence of both a substrate-sparing strategy and higher damage in the liver. A higher respiratory efficiency during reproduction suggests the liver maximizes ATP production from the substrate it takes in, a strategy that could facilitate greater substrate use by the mammary gland. Although lactating females displayed a higher basal respiratory rate that limits ROS production, lactating females also displayed higher oxidative damage than non-reproductive females, which could have long-term negative effects on longevity.
The disposable soma theory predicts that the increased energetic demand of reproduction will decrease allocation to self-maintenance, allowing for the accumulation of harmful damage to mitochondrial DNA. This damage results in the replication and propagation of inefficient mitochondria post-reproduction. To evaluate the impact of reproduction on maintenance, and thus longevity, in chapter 2 I completed measurements of mitochondrial efficiency, oxidative damage, and antioxidant capacity at least one month following reproduction to exclude the immediate metabolic changes associated with pregnancy and lactation. While oxidative damage is higher in liver mitochondria post-reproduction, I found no evidence that this damage adversely affects mitochondrial function and, thus, would not be a major contributor to senescence. Combined, my results suggest that while there is a momentary cost to self-maintenance during reproduction and a lasting increase in free radical production, there is no long-term adverse affect on mitochondrial function, calling into question the role that mitochondria play in the tradeoff between reproduction and longevity.||en_US