Title

Intermittent fasting and caloric restriction interact with genetics to shape physiological health in mice.

Document Type

Article

Publication Date

1-2022

Publication Title

Genetics

Keywords

Caloric Restriction

JAX Source

Genetics 2022 Jan; 220(1):iyab157

Volume

220

Issue

1

ISSN

1943-2631

PMID

34791228

DOI

https://doi.org/10.1093/genetics/iyab157

Abstract

Dietary interventions can dramatically affect physiological health and organismal lifespan. The degree to which organismal health is improved depends upon genotype and the severity of dietary intervention, but neither the effects of these factors, nor their interaction, have been quantified in an outbred population. Moreover, it is not well understood what physiological changes occur shortly after dietary change and how these may affect the health of an adult population. In this article, we investigated the effect of 6-month exposure of either caloric restriction (CR) or intermittent fasting (IF) on a broad range of physiological traits in 960 1-year old Diversity Outbred mice. We found CR and IF affected distinct aspects of physiology and neither the magnitude nor the direction (beneficial or detrimental) of effects were concordant with the severity of the intervention. In addition to the effects of diet, genetic variation significantly affected 31 of 36 traits (heritabilities ranged from 0.04 to 0.65). We observed significant covariation between many traits that was due to both diet and genetics and quantified these effects with phenotypic and genetic correlations. We genetically mapped 16 diet-independent and 2 diet-dependent significant quantitative trait loci, both of which were associated with cardiac physiology. Collectively, these results demonstrate the degree to which diet and genetics interact to shape the physiological health of adult mice following 6 months of dietary intervention.

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