Nutritional Programming of Lifespan by FOXO Inhibition on Sugar-Rich Diets

Adam J Dobson,Marina Ezcurra,Charlotte E Flanagan,Adam C Summerfield,Matthew D.W Piper,David Gems,Nazif Alic

doi:10.1016/j.celrep.2016.12.029

Adam J Dobson, Marina Ezcurra + Show 5 more

Open Access

https://doi.org/10.1016/j.celrep.2016.12.029

Copy DOI

Journal: Cell Reports	Publication Date: Jan 1, 2017
Citations: 54	License type: cc-by

Affiliation: University College London, Monash University

Abstract

SummaryConsumption of unhealthy diets is exacerbating the burden of age-related ill health in aging populations. Such diets can program mammalian physiology to cause long-term, detrimental effects. Here, we show that, in Drosophila melanogaster, an unhealthy, high-sugar diet in early adulthood programs lifespan to curtail later-life survival despite subsequent dietary improvement. Excess dietary sugar promotes insulin-like signaling, inhibits dFOXO—the Drosophila homolog of forkhead box O (FOXO) transcription factors—and represses expression of dFOXO target genes encoding epigenetic regulators. Crucially, dfoxo is required both for transcriptional changes that mark the fly’s dietary history and for nutritional programming of lifespan by excess dietary sugar, and this mechanism is conserved in Caenorhabditis elegans. Our study implicates FOXO factors, the evolutionarily conserved determinants of animal longevity, in the mechanisms of nutritional programming of animal lifespan.

Highlights

Age is the main risk factor for a plethora of chronic human illnesses (Niccoli and Partridge, 2012)
We show that sugar regulates the activity of the Drosophila forkhead box O (FOXO) transcription factor (TF) to set up gene expression changes that mark the fly’s nutritional history
We found that the median lifespan of flies that had been fed 83 excess of sugar (83S) for 3 weeks was reduced (7%; Figure 1B)

Summary

Introduction

Age is the main risk factor for a plethora of chronic human illnesses (Niccoli and Partridge, 2012). Chronic diseases are on the rise globally, due in part to aging populations (Christensen et al, 2009) and due to the increasing consumption of unhealthy diets dominated by highly processed, low-cost foods (Dearden and Ozanne, 2015; Lustig et al, 2012). Sugar consumption has tripled over the last 50 years and is linked to a range of detrimental health outcomes (Lustig et al, 2012). These conditions underlie a pandemic of metabolic disorders, such as obesity and diabetes, which amplify the disease burden of an increasingly aged population

Results

Discussion

Conclusion