Sexual dimorphism in the nutritional requirement for adult lifespan in Drosophila melanogaster

Abstract

The nutritional requirements of Drosophila have mostly been studied for development and reproduction, but the minimal requirements for adult male and female flies for lifespan have not been established. Following development on a complete diet, we find substantial sex difference in the basic nutritional requirement of adult flies for full length of life. Relative to females, males require less of each nutrient, and for some nutrients that are essential for development, adult males have no requirement at all for lifespan. The most extreme (and surprising) sex differences were that chronic cholesterol and vitamin deficiencies had no effect on the lifespan of adult males, but they greatly decreased lifespan in females. Female oogenesis rather than chromosomal karyotype and mating status is the key cause of this gender difference in life‐sustaining nutritional requirements. These data are important to the way we understand the mechanisms by which diet modifies lifespan.

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

“…This approach is the opposite of, but complementary to, the already recognised strategies to extend lifespan by DR, which reduce maternal investment into reproduction by decreasing the dietary protein : carbohydrate ratio (Mair et al, 2005;Lee et al, 2008;Skorupa et al, 2008) or by treating the animals with rapamycin that suppresses TOR and reduces reproduction (Bjedov et al, 2010;Harrison et al, 2009;Liu & Sabatini, 2020). It is also consistent with our recent work that showed non-reproducing adult males and genetically sterile females suffer little to no lifespan cost when sterol deprived, which is presumably because they conserve sterols which would otherwise be depleted by reproduction (Wu et al, 2020).…”

“…In mechanistic work, the increased lifespan under dietary restriction has been attributed to the benefits of reduced dietary protein, which enhances proteome maintenance via reduced TOR signalling (Harrison et al, 2009;Partridge et al, 2011;Kapahi et al, 2017;Piper et al, 2017;Sabatini, 2017;Dobson et al, 2018;Liu & Sabatini, 2020). However, we have shown that flies on a high protein : carbohydrate diet, in which TOR signalling would be expected to remain high, can still sustain a long lifespan if supplemented with cholesterol, or alternatively, if the cost of reproduction on sterol stores is removed by making flies infertile (Wu et al, 2020). This demonstrates that the major improvement to lifespan observed on low protein diets is not the result of enhanced proteostasis, but is instead, a side effect of avoiding sterol depletion caused by egg production.…”

“…However, yeast also contains all of the fly's other essential macro and micronutrients whose relative proportions can change, and thus possibly interact with protein and carbohydrates to dictate life history outcomes. We have previously found that depriving adult female flies of a source of sterols, an essential micronutrient for insects, imposes a minor cost on reproduction, but a substantial (>50%) cost to lifespan (Piper et al, 2014;Wu et al, 2020). These data indicate that yeast sterol levels may contribute to the effects on lifespan of protein and carbohydrate.…”

“…Although protein is key, females must transfer dozens of nutrients into eggs for future embryo formation and not all of these components contribute to the flies' decision to produce eggs ( Piper et al, 2014;Mirth et al, 2019;Wu et al, 2020). This means that high protein diets might drive mothers to produce eggs at a faster rate than they can support if the diet contains insufficient levels of the other components that are required to make eggs.…”

Caloric restriction increases levels of taurine in the intestine and stimulates taurine uptake by conjugation to glutathione

“…Therefore, the increased levels of BAs and taurine in the intestine during CR could contribute to the previously described phenotype. Importantly, taurine supplementation, similary like CR has been shown to reduce endoplasmic reticulum stress and extend lifespan in C. elegans (Kim et al, 2010, Wu et al, 2020). Consequently, taurine has already been suggested as a supplement mimicking beneficial outcomes of CR (Nishizono et al, 2017).…”