Role of Obesity and Aging on Intestinal Stem Cell Function

Abstract

Changes of somatic stem cell (SSC) functionality has been proposed to contribute to tissue and organismal aging. Because the effects of diet and aging on SSC function can impact organ senescence and longevity, the need to determine the differences between young and old SSC in vivo and elucidating general principles of how SSC respond to diet and aging signals are critically important for many aspects of aging and regenerative biology. However, we have a limited understanding of how SSCs change with age and under different diet conditions as well as how modifying aged SSCs affects organ function. Given the important contributions of the intestine to metabolism, growth, and immunity, we used Drosophila intestinal stem cells (ISCs) as a model system to understand these questions. We show that there is an age‐dependent increase in ISC numbers. Furthermore, using a novel High Fat Diet‐induced obesity model, we also see a similar increase in ISC numbers. Both of these age and High Fat Diet‐induced ISC phenotypes can be prevented by decreasing the insulin‐nutrient sensing Target of Rapamycin (TOR) signaling pathways. Thus, these results show that reduction of insulin‐metabolic pathways provides protection against age‐ and high fat diet‐dependent changes in the ISCs and intestine. Future work will look at how other dietary conditions like Dietary Restriction can also modify the ISC aging phenotypes. These results are highly relevant to metabolic diseases like obesity and diabetes as well as colorectal cancer. In many species, reduction of insulin‐nutrient sensing pathways promotes longevity and these results suggest longevity may be linked to stem cell aging via alterations of these pathways.