THE EFFECT OF REPRODUCTION ON CELLULAR SENESCENCE MARKERS IN THE BRAIN, LIVER, AND SKELETAL MUSCLE OF WILD-DERIVED FEMALE HOUSE MICE
May 17th, 2022 -American Aging Association (AGE) Annual Meeting
Across taxa, observations indicate reproduction reduces longevity. Intraspecific observations indicate reproductive output declines with increasing age thus suggesting reproduction requires maternal physiological investment. The Disposable Soma theory suggests reproductive females in good condition reallocate resources from somatic maintenance to facilitate reproduction. It is assumed the somatic stores decrease with age, but how reproduction reduces longevity remains unclear.
The aim of this project is to understand why somatic reserves deplete due to reproduction using wild-derived female house mice maintained in semi-natural enclosures to keep the study within an ecologically relevant context.
We hypothesized reproduction results in early onset cellular senescence normally associated with advanced age and age-related pathologies thus resulting in reduced longevity.
To test our hypothesis, we allowed a population of mice aged 1.4 yrs to breed continuously for 10 months in semi-natural enclosures along with age-matched non-reproductive controls. A group of aged mice average 2.3 yrs were maintained in rodent boxes. A set of middle aged animals maintained in rodent boxes at an average age of 1.4 yrs were used as the control to assess the effect of age on our variables.
If reproduction resulted in a cost to maternal physiology such that it advances somatic aging and reduced longevity, then we predicted reproduction would affect relative organ mass and result in histopathology of the brain, liver, and hindlimb skeletal muscle.
We further predicted reproduction would reduce longevity marker SIRT1 resulting in increased levels of IL-6 to promote inflammaging, while decreasing mitophagy markers (PINK1 and PARKIN) and redox metabolite NAD+.
Although we detected no histopathology, we did observe increased liver, spleen, kidney, and heart masses due to reproduction. We also observed reduced brain and muscle mass due to reproduction. Finally, we observed evidence of senescence phenotypes and impaired mitophagy in the brain due to reproduction.
My participation in AGE 2022 was made possible due to receiving a virtual travel award as an AGE Early Career Scholar.