Effects of aging on the gut tube of the short-lived Turquoise killifish: Reduced intestinal stem cell activity associated by altered gene expression that is reversed by intermittent fasting

The process of aging is associated with a decline in cellular, tissue, and organ function, which give rise to a range of health issues. Mounting evidence indicates that dietary restriction counters age-dependent effects and increases and enhances health and longevity in whole organisms, while less is known of aging and nutrition on individual organs of an organism. Here, we studied the responsible organ for nutrient uptake, the intestinal tube, along the lifetime of an organism. A longitudinal study was conducted on the morphology and gene expression of the gut tubes of the very short-lived aging model system African turquois killifish (Nothobranchius furzeri). The aim was to investigate the age and nutrition-related effects on gut tissue preservation at stages corresponding to human newborn, adolescence, adult and old age. The intestinal mucosa is characterized by folds and intervening interfold regions, in which the intestinal stem cells were localized. The stem cells were found to occur in clusters and that the cycling time of stem cells extends at old age. Concomitantly, we found a reduction in intestinal length and volume with age. Age-dependent gene expression revealed significant alterations in the expression of peripheral circadian clock genes and marker genes of stem cell niches. Notably, the majority of these genes retained their adult gene expression levels at old age after dietary restriction. Thus, our results demonstrate that the decline of structural intestinal tissue homeostasis is caused by a declining activity of stem cells, and that these effects are counteracted by dietary restriction Overall design: Gene expression profiling by RNA-seq of whole intestine at week 10, at week 20 and at week 20 with dietary restriction.