Lifelong calorie restriction affects indicators of colonic health in aging C57Bl/6J mice

Dieuwertje E. G. Kok (Lead Author), Fenni Rusli, Benthe van der Lugt, Carolien Lute, Luca Laghi, Stefano Salvioli, Gianfranco Picone, Claudio Franceschi, Hauke Smidt, Jacques Vervoort, Ellen Kampman, Michael Müller, Wilma T. Steegenga

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Diminished colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an effective strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here, we report the effects of lifelong CR on indicators of colonic health in aging C57Bl/6J mice. Compared to an ad libitum control and moderate-fat diet, 30% energy reduction was associated with attenuated immune- and inflammation-related gene expression in the colon. Furthermore, expression of genes involved in lipid metabolism was higher upon CR, which may point towards efficient regulation of energy metabolism. The relative abundance of bacteria considered beneficial to colonic health, such as Bifidobacterium and Lactobacillus, increased in the mice exposed to CR for 28 months as compared to the other diet groups. We found lower plasma levels of interleukin 6 and lower levels of various metabolites, among which bile acids, in the colonic luminal content of CR-exposed mice as compared to the other diet groups. Switching from CR to an ad libitum moderate-fat diet at old age (24 months) revealed remarkable phenotypic plasticity in terms of gene expression, microbiota composition and metabolite levels, although expression of a subset of genes remained CR-associated. This study demonstrated in a comprehensive way that CR affects indicators of colonic health in aging mice. Our findings provide unique leads for further studies that need to address optimal and feasible strategies for prolonged energy deprivation, which may contribute to healthy aging.
Original languageEnglish
Pages (from-to)152–164
Number of pages13
JournalJournal of Nutritional Biochemistry
Early online date20 Mar 2018
Publication statusPublished - Jun 2018


  • aging
  • calorie restriction
  • colonic health
  • gene expression
  • gut microbiota
  • metabolites

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