A dietary sterol trade-off determines lifespan responses to dietary restriction in Drosophila melanogaster females.

Brooke Zanco,Carla M Sgrò,Christen K Mirth,Matthew Dw Piper

doi:10.7554/elife.62335

Abstract

Diet plays a significant role in maintaining lifelong health. In particular, lowering the dietary protein: carbohydrate ratio can improve lifespan. This has been interpreted as a direct effect of these macronutrients on physiology. Using Drosophila melanogaster, we show that the role of protein and carbohydrate on lifespan is indirect, acting by altering the partitioning of limiting amounts of dietary sterols between reproduction and lifespan. Shorter lifespans in flies fed on high protein: carbohydrate diets can be rescued by supplementing their food with cholesterol. Not only does this fundamentally alter the way we interpret the mechanisms of lifespan extension by dietary restriction, these data highlight the important principle that life histories can be affected by nutrient-dependent trade-offs that are indirect and independent of the nutrients (often macronutrients) that are the focus of study. This brings us closer to understanding the mechanistic basis of dietary restriction.

Highlights

Dietary restriction, called calorie restriction, is a moderate reduction in food intake that extends healthy lifespan across a broad range of taxa, from yeast to primates (Chapman and Partridge, 1996; Colman et al, 2009; Lin et al, 2002; McCay et al, 1935)
We selected dietary protein and carbohydrate concentrations that we know to elicit the full range of lifespan and fecundity responses to dietary restriction (Lee et al, 2008; Piper et al, 2014, Piper et al, 2017; Ma et al, 2020)
Egg production showed a linear, positive correlation with dietary protein content (Figure 1, Supplementary file 1), while lifespan showed a peak at intermediate protein (66 d median at 10.7 g/l), and fell away at both higher (49 d median at 33.1 g/l) and lower (43 d median at 5.2 g/l) concentrations (Figure 1a–b, Supplementary file 2)

Summary

Introduction

Called calorie restriction, is a moderate reduction in food intake that extends healthy lifespan across a broad range of taxa, from yeast to primates (Chapman and Partridge, 1996; Colman et al, 2009; Lin et al, 2002; McCay et al, 1935) The generality of this observation has inspired confidence that the health benefits of dietary restriction might be employed to improve human ageing (Campisi et al, 2019). The most prominent theoretical explanation has been the disposable soma theory, which employs resource-based trade-offs to explain how dietary restriction can benefit lifespan (Kirkwood, 1977; Shanley and Kirkwood, 2000) This theory postulates that organisms will maximise fitness by strategically partitioning limiting dietary energy either to reproduction or somatic maintenance, the latter determining lifespan. This means that longer lifespan is inevitably coupled with reduced reproduction because both traits compete for the same limiting resource

Methods

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Discussion

Conclusion