Intestinal SIRT1 in the regulation of intestinal tissue homeostasis

The goal of this project is to investigate the role of SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase, in the regulation of intestinal tissue integrity. Using a mouse model with specific deletion of SIRT1 in intestinal epithelium (SIRT1 iKO mice), we recently discovered that deletion of intestinal SIRT1 in mice age-dependently elicits NF-κB signaling and other stress response pathways, activates intestinal secretory cells, enhances spontaneous inflammation, and alters commensal gut microbial composition. To understand the molecular mechanisms underlying these age-dependent phenotypes, we examined the transcriptomes of young (6-8 week old) and aged (24-month old) ilea and aged colons from Flox controls and SIRT1 iKO mice by microarray analysis. Total RNA were extracted from ileum and colon tissues of 3-4 young and aged Flox controls and SIRT1 iKO mice, and gene expression profiles were analyzed using Agilent Whole Mouse Genome 4x44 multiplex format oligo arrays (014868) (Agilent Technologies, Santa Clara, CA), following the Agilent 1-color microarray-based gene expression analysis protocol.