Abstract

Dietary intervention has received considerable attention as an approach to extend lifespan and improve aging. However, questions remain regarding optimal dietary regimes and underlying mechanisms of lifespan extension. Here, we asked how an increase of glucose in a chemically defined diet extends the lifespan of adult Drosophila. We showed that glucose-dependent lifespan extension is not a result of diminished caloric intake, or changes to systemic insulin activity, two commonly studied mechanisms of lifespan extension. Instead, we found that flies raised on glucose-supplemented food increased the expression of cell adhesion genes, delaying age-dependent loss of intestinal barrier integrity. Furthermore, we showed that chemical disruption of the gut barrier negated the lifespan extension associated with glucose-treatment, suggesting that glucose-supplemented food prolongs adult viability by enhancing the intestinal barrier. We believe our data contribute to understanding intestinal homeostasis, and may assist efforts to develop preventative measures that limit effects of aging on health.