Sterol deprivation elicits a somatic cost exclusively towards Drosophila melanogaster males that are reproductively-active

The extension of lifespan via the restriction of nutrients (dietary restriction) remains a poorly-understood phenomenon both within the context of life-history theory, and at a mechanistic level, despite presenting as an ideal opportunity for targeted interventions. A body of evidence has formed, disputing the classical model of a simple, strategic allocation of energy towards either reproduction or somatic maintenance; macronutrient, and more recently, micronutrient intake (like methionine) has been shown to play a role in mediating plastic responses in fitness components, often obscuring an observable physiological trade-off. Sterols are non-energy yielding, and their depletion in the female fruit fly (Drosophila melanogaster) has previously been shown to mediate a cost to lifespan. Flies are sterol auxotrophs, necessitating uptake from the environment, and are additionally largely post-mitotic, so may only require for maintaining reproductive output. The manipulation of dietary sterol availability in the fly therefore presents a unique opportunity to test nutrient-specific costs of reproduction. Here, we utilise a fully chemically-defined diet with an exome-matched amino acid ratio to specifically deplete cholesterol from the nutritional environment, and find costs are realised solely in the lifespan of frequently-mating males, with no concomitant cost realised in reproductive fitness. We cautiously interpret these findings as the preferential sequestering of cholesterol from the soma to maximise reproductive fitness, but also suggest a potential role of steroid hormone biosynthesis dysregulation. In contrast to previous work, we additionally find that predictions derived from life-history theory are indeed generalisable to male flies, since males exhibit a nutritional trade-off between high- and low-protein diets, suggestive of disparate strategies. Given the attenuated lifespan responses to macronutrient change, we speculate individuals may be more tolerant to overconsumption of dietary proteins when amino acid ratios are matched to the needs of the consumer. These data further reinforce the importance of considering both the often-overlooked costs of reproduction in males, and the macronutritional context of a micronutritional intervention.