Surgical Studies of Aging and the Gut

Transfer Proposal - Over the last four years our work has progressed quite nicely to identify effects of aging on the colonic mucosa. Colorectal cancer is more prevalent in aged individuals and likewise is more prevalent in the distal part of the colon and rectum. We previously showed increased levels of phosphorylated Akt, an indicator of PI3K activation, tended to increase from proximal to distal colon, suggesting that PI3K is more strongly activated in the distal colon compared to the proximal colon. Quite surprisingly, we also showed that levels of ~-catenin dramatically increased in the distal colon compared to the proximal colon, We have collaborated with Dr. Susan Henning at the University of North Carolina to analyze enriched fractions of colonic stem cells to determine differences in Pl3K activation and expression patterns in young and aged colonic stem cells. We are continuing to work with Dr. Henning to optimize separation techniques an'd currently are working on a joint publication describing the isolation of stem cells in colonic mucosa from young mice compared with aged colonic stem cells.