Investigating mitochondria-induced premature aging due to reproduction and environment in semi-natural enclosed wild-derived house mice

Abstract

Reproduction is a highly energetic process requiring both prenatal and postnatal investment for female mammals. Under the disposable soma theory (DST), prenatal investment includes reallocation of resources used to maintain maternal somatic tissue towards offspring during gestation. During postnatal investment, reallocation continues during lactation. Across taxa, female reproductive success is observed to decline with increasing age suggesting physiological limits for investment, and high reproductive output is associated with reduced longevity. Several hypotheses suggest maternal physiology incurs a cost due to reproduction and that reproduction trades off with longevity. Oxidative stress (OS) is hypothesized to explain the tradeoff suggesting mitochondria-generated free radical damage impairs investment into reproduction. Although OS damage to mitochondrial DNA (mtDNA), proteins and lipids is possible, hormetic mechanisms found to mitigate oxidative damage have left the perspective challenged. Traditionally, research on mitochondrial function in reproduction is conducted in inbred lab mice and rats resulting in data likened to cloned populations prone to high OS, maintained in asocial conditions, not representative of natural populations comprised of individuals with unique life-histories. Here I use a genetically diverse population of wild-derived Mus musculus maintained in ecologically relevant conditions to investigate the tradeoff between reproduction and longevity. I hypothesized reproduction prematurely ages maternal soma through mitochondrial dysfunction, however, I found reproduction extends the healthspan of maternal soma and that environmental stressors are stronger contributors to metabolic aging. Out of the brain, liver and hindlimb skeletal muscle tissues, liver tissue incurred OS damage due to reproduction only. While efforts to repair the soma was observed postpartum in reproductives, this was not observed in aged hosts. This study adds to the growing body of works challenging the cost of reproduction hypothesis (CORH).