Selective breeding for high levels of voluntary exercise in mice does not reduce lifetime reproductive success or lifespan
Authors: Whitehead Natalie , Schwartz Nicole , Cabrera Haley , Kim Matthew , Pineiro Lucas , Lampman William , Holt Natalie 
Published: May 2024

The ways locomotor abilities may interact with life history traits are complicated and may involve shifts in resource allocation. For example, individuals that have large litters may have reduced energy available to support the organ systems required for high locomotor performance abilities. Alternatively, energy spent on excess physical activity might subtract from that available for somatic maintenance, and thus be negatively related to lifespan or to other fitness components that contribute to lifetime reproductive success (LRS). We studied lifetime reproductive successes, life span, and health span in mice from a long-term (>100 generations) artificial selection experiment that includes 4 replicate High Runner (HR) lines bred for voluntary locomotor activity on wheels and 4 lines that serve as non-selected Controls (C). Since reaching selection limits at around generation 17-27 (depending on line and sex), the HR mice have been running ~3-fold farther on a daily basis as compared with C mice, for both sexes, which leads to substantially increased energy expenditure and food consumption. Importantly, when housed without wheels, HR mice are not only more active, but also consume more food than C mice. In the present study, we tested for differences in LRS between the HR and C lines. We are also comparing lifespan (median, maximum) and healthspan (e.g., by measurement of maximal oxygen consumption [VO2max] during forced exercise and maximal sprint speed. Twelve male-female pairs per line from generation 97 (born Oct. 2021) are being maintained until their end of life. In addition to total number of pups weaned per pair, we record components of LRS, such as age at first and last litter for the pairs, number of litters, and inter-birth intervals. Here, we present a subset of results through the first 2+ years of the experiment. Only two of 100 pairs never gave birth to any litters, and 89 of 100 pairs weaned at least one litter. The total number of litters born to pairs ranged from 0 to 12, and the number of litters from which at least one pup was weaned ranged from 0 to 11, with a mean of 3.96+0.73 (SE) for C lines and 3.43+0.65 for HR lines (P=0.61). The total number of pups weaned (our measure of LRS) ranged from 0 to 80, with a mean of 29.1+8.1 (SE) for C lines and 25.8+4.4 for HR lines (P=0.73). Thus, we found no evidence that Darwinian fitness has been reduced by artificial selection for high voluntary exercise. As of 1 Nov. 2023, approximately 17% of the breeders are still alive, and preliminary analyses do not indicate significant differences between the C and HR lines in median or maximum lifespan. Supported by U.S. National Science Foundation grant IOS-2038528. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.