The effect of resveratrol on lifespan depends on both gender and dietary nutrient composition in Drosophila melanogaster

Abstract

Resveratrol, a polyphenolic compound, has been shown to extend lifespan in different organisms. Emerging evidence suggests that the prolongevity effect of resveratrol depends on dietary composition. However, the mechanisms underlying the interaction of resveratrol and dietary nutrients in modulating lifespan remain elusive. Here, we investigated the effect of resveratrol on lifespan of Drosophila melanogaster fed diets differing in the concentrations of sugar, yeast extract, and palmitic acid representing carbohydrate, protein, and fat, respectively. Resveratrol at up to 200 μM in diets did not affect lifespan of wild-type female flies fed a standard, restricted or high sugar-low protein diet, but extended lifespan of females fed a low sugar-high protein diet. Resveratrol at 400 μM extended lifespan of females fed a high-fat diet. Lifespan extension by resveratrol was associated with downregulation of genes in aging-related pathways, including antioxidant peroxiredoxins, insulin-like peptides involved in insulin-like signaling and several downstream genes in Jun-kinase signaling involved in oxidative stress response. Furthermore, resveratrol increased lifespan of superoxide dismutase 1 (sod1) knockdown mutant females fed a standard or high-fat diet. No lifespan extension by resveratrol was observed in wild-type and sod1 knockdown males under the culture conditions in this study. Our results suggest that the gender-specific prolongevity effect of resveratrol is influenced by dietary composition and resveratrol promotes the survival of flies by modulating genetic pathways that can reduce cellular damage. This study reveals the context-dependent effect of resveratrol on lifespan and suggests the importance of dietary nutrients in implementation of effective aging interventions using dietary supplements.

Fig. 1

The effect of resveratrol on the lifespan of wild type Canton S flies fed the standard base and calorie restriction (CR) diets. a–b Lifespan curves of females and males fed the standard base diet supplemented with 0, 100, or 200 μM resveratrol (Resv). c–d Lifespan curves of females and males fed the CR diet supplemented with 0, 100, or 200 μM resveratrol. The number of flies in each trial is more than 100. No effect supplementation of resveratrol does not extend lifespan under the diet condition specified

Fig. 2

The effect of resveratrol on the lifespan of wild type Canton S flies fed the high sugar–low protein (HS–LP) and low sugar–high protein (LS–HP) diets. a–b Lifespan curves of females and males fed the HS–LP diet supplemented with 0, 100, or 200 μm resveratrol (Resv). c–d Lifespan curves of females and males fed the LS-HP diet supplemented with 0, 100, or 200 μm resveratrol. The number of flies in each trial is more than 100. No effect supplementation of resveratrol does not extend lifespan under the diet condition specified; Increase supplementation of resveratrol extends lifespan under the specified diet condition

Fig. 3

The effect of resveratrol on the lifespan of wild type Canton S flies fed the high-fat diet. a Lifespan curves of females fed the high diet supplemented with 0, 200, or 400 μM resveratrol (Resv). b Food intake of females fed the high-fat diet supplemented with 0 or 400 μM resveratrol. The bar graph shows average daily food intake in volume per fly for females 2 weeks old in three consecutive days. The error bars indicate standard error. c Lifespan curves of males fed the high diet supplemented with 0, 200, or 400 μM resveratrol. The number of flies in each trial is more than 100. No effect supplementation of resveratrol does not extend lifespan under the specified diet condition; Increase supplementation of resveratrol extends lifespan under the specified diet condition

Fig. 4

The effect of resveratrol on gene expression in Canton S female flies fed the low sugar–high protein (LS–HP) diet as determined by quantitative PCR (qPCR). a Expression patterns of metabolism-related genes in flies fed the LS–HP diet with or without 400 μM resveratrol. b Expression patterns of oxidative stress-related genes in flies fed the LS–HP diet with or without 400 μm resveratrol. The relative transcript levels of all genes are in arbitrary units (a. u.) after being normalized to the transcript level of rpL32. The values are expressed as means ± standard error. Four to six biologically independent samples were used in qPCR for each diet. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001 based on Student’s t test

Fig. 5

The effect of resveratrol on gene expression and food intake in Canton S female flies fed the high-fat diet as determined by qPCR. a Expression patterns of metabolism-related genes in flies fed the high-fat diet with or without 400 μM resveratrol. b Expression patterns of oxidative stress-related genes in flies fed the high-fat diet with or without 400 μM resveratrol. The relative transcript levels of all genes are in arbitrary units (a.u.) after being normalized to the transcript level of rpL32. Four to six biological independent samples were used in qPCR for each diet. ^*p < 0.05, ^**p < 0.01, ^***p < 0.001 based on Student’s t test

Fig. 6

The effect of resveratrol on the lifespan of sod1RNAi flies fed the standard base and high-fat diets. a–b Lifespan curves of sod1RNAi females and males fed the standard base diet supplemented with 0, 200, or 400 μm resveratrol. c–d Lifespan curves of sod1RNAi females and males fed the high-fat diet supplemented with 0, 200, or 400 μm resveratrol. The number of flies in each trial is more than 100. Increase and decrease marked in the panel indicate that supplementation of resveratrol extends and reduces lifespan, respectively under the specified diet condition