Nutritional Programming of the Lifespan of Male Drosophila by Activating FOXO on Larval Low-Nutrient Diet

Abstract

Nutrition during the developmental stages has long-term effects on adult physiology, disease and lifespan, and is termed nutritional programming. However, the underlying molecular mechanisms of nutritional programming are not yet well understood. In this study, we showed that developmental diets could regulate the lifespan of adult Drosophila in a way that interacts with various adult diets during development and adulthood. Importantly, we demonstrated that a developmental low-yeast diet (0.2SY) extended both the health span and lifespan of male flies under nutrient-replete conditions in adulthood through nutritional programming. Males with a low-yeast diets during developmental stages had a better resistance to starvation and lessened decline of climbing ability with age in adulthood. Critically, we revealed that the activity of the Drosophila transcription factor FOXO (dFOXO) was upregulated in adult males under developmental low-nutrient conditions. The knockdown of dFOXO, with both ubiquitous and fat-body-specific patterns, can completely abolish the lifespan-extending effect from the larval low-yeast diet. Ultimately, we identify that the developmental diet achieved the nutritional programming of the lifespan of adult males by modulating the activity of dFOXO in Drosophila. Together, these results provide molecular evidence that the nutrition in the early life of animals could program the health of their later life and their longevity.

The Involvement of Peroxiporins and Antioxidant Transcription Factors in Breast Cancer Therapy Resistance

“…FOXO proteins regulate cell cycle arrest and apoptosis, but also play a crucial role in differentiation [127]. FOXO homologues in C. elegans and the silkworm are active in lifespan extension [128,129]. In humans, FOXO3 is responsible for longevity [130].…”

The Intervention of Diet on Energy Metabolism

“…Lastly, a study by Gao et al [3] described the effect of developmental diets (a low-yeast diet) on regulating the lifespan of adult Drosophila during development and adulthood. It was demonstrated that a developmental diet achieved the nutritional programming of the lifespan of adult males by modulating the activity of dFOXO in Drosophila.…”