Abstract
ABSTRACTDietary 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 melanogaster. 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.
Highlights
As nutrition has established impacts on health, optimizing feeding regimes to promote healthy aging has received considerable attention (Kalache et al, 2019)
Glucose-supplemented holidic food promotes maintenance of energy stores with age In a longitudinal study of relationships between nutrition, age, and metabolism, we found that, regardless of genetic background, glucose-supplemented (100 g/L) holidic food extends the lifespan of adult Drosophila compared to unmodified holidic food, in males (Galenza et al, 2016)
For the remainder of this study we determined the effects of holidic food (HF), and 50 g/L glucose-supplemented holidic food (GSF) on health and longevity
Summary
As nutrition has established impacts on health, optimizing feeding regimes to promote healthy aging has received considerable attention (Kalache et al, 2019). Nutritional deficiencies increase risk of developing a number of age-related chronic diseases, but we have limited understanding of dietary interventions that counter agedependent deterioration of tissue and organ function (Shlisky et al, 2017). Model organisms, including Drosophila melanogaster, are excellent tools to study interactions between nutrition and organ function with age (Fontana and Partridge, 2015; Lee et al, 2015; Piper and Partridge, 2017). Researchers can grow flies on chemically defined holidic media that allow investigators to quantify effects of macronutrients on health and lifespan (Piper et al, 2014). Nutritional geometry work emphasized the importance of relative macronutrient levels for Drosophila fitness, and revealed that low
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