GSE100701
Lifelong calorie restriction and markers of colonic health in aging mice
Diminishment of colonic health is associated with various age-related pathologies. Calorie restriction (CR) is an efficient strategy to increase healthy lifespan, although underlying mechanisms are not fully elucidated. Here we report the effects of lifelong CR on markers of colonic health in aging mice. We show that 30% energy reduction, as compared to a control (C) and moderate-fat (MF) diet, is associated with attenuated immune-related gene expression and lower levels of bile acids in the colon. Pronounced shifts in microbiota composition, together with lowered plasma levels of interleukin 6, in mice exposed to CR are in line with these findings. Furthermore, expression of genes involved in lipid metabolism was higher upon CR as compared to C and MF, pointing towards efficient regulation of energy metabolism. Switching from CR to an ad libitum MF diet at old age revealed remarkable phenotypic plasticity, although expression of a small subset of genes remained CR-associated. This research demonstrates that CR beneficially affects markers of colonic health in aging mice and as such may attenuate the progressive age-related decline in health. Overall design: Male C57BL/6J mice were randomized to different dietary regimens starting at the age of 9 weeks. Mice were lifelong fed either a semi-synthetic control diet consisting of 10E% of fat (C), a CR diet without malnutrition (30% energy reduction compared to the C diet) or a moderate-fat (MF) diet consisting of 25E% of fat. All diets, except the CR diet, were fed ad libitum. A subgroup of mice on CR was switched to the MF diet at the age of 24 months until sacrifice at 28 months. Upon sacrifice at 6 or 28 months of age, colonic scrapings were collected and RNA was isolated for microarray analyses.