Age and diet interact to shape body weight and lifespan of DO mice
Authors: Kevin Wright 1; Andrew Deighan 2; Andrea Di Francesco 1; Adam Freund 1; Vladimir Jojic 1; Gary Churchill 2; Anil Raj 1
Affiliations: 1) Calico Life Sciences, LLC; 2) The Jackson Laboratory
Keywords: Complex traits
It is largely unknown the degree to which age shapes additive genetic and genotype-environment interaction effects to shape quantitative traits. We used a linear mixed model to quantify age- and diet-dependent genetic contributions to a classic quantitative trait (body weight) measured throughout the life of Diversity Outbred female mice subject to five dietary treatments. We observed that heritability of body weight declined with age under all diets, except the most extreme calorie restriction diet, which remained high throughout adulthood. We identified age- and diet-specific body weight loci and found all allelic effects were consistently positive or negative at one age and neutral at other ages. We found no evidence of allelic effect trade-offs with respect to age. We measure the association between these body weight effect alleles and animal lifespan and conclude these results are inconsistent with predictions arising from Williams’ (1957) antagonistic pleiotropy theory of aging.