High-sugar diet switches sex-specific longevity responses to capsaicin in Drosophila melanogaster

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Abstract

Despite known benefits in normal diet, capsaicin's effects under obesogenic conditions remain unexplored. Based on capsaicin's established metabolic benefits, we hypothesized that capsaicin supplementation would extend lifespan in both male and female Drosophila melanogaster under high-sugar diet conditions. Here, we tested the impacts of capsaicin on longevity in Drosophila melanogaster fed a high-sugar diet. Contrary to our hypothesis, a sex-specific reversal was found: capsaicin at 1–100 µmol/L significantly extended the median lifespan of male flies by 10.52% (P < 0.01), yet showed no benefit in females. This was in contrast to our previous finding where capsaicin increased female lifespan on standard diet. Such a diet-switched sex specificity highlights that capsaicin's effects are not only sex-dependent but also modulated by metabolic interactions with dietary conditions. Furthermore, the lifespan-extending effects of capsaicin were concentration-dependent, suggesting potential hormetic mechanisms. These novel findings underscore the complex interplay between bioactive compounds, host metabolism and sex-specific responses in the context of obesity-inducing diets.

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