Curcumin Induces Transgenerational and Sex-Specific Effects on Lifespan, Gene Expression, and Metabolism in the Fruit Fly Drosophila melanogaster

Abstract

Curcumin is a bioactive compound found in turmeric (Curcuma longa) and is widely recognized for its health-promoting effects, including anti-inflammatory, antioxidant, and anti-carcinogenic properties. It can also mediate epigenetic effects by inhibiting histone acetylases (HATs) and deacetylases (HDACs) but the transgenerational context has not been studied in detail. Here, we used the fruit fly (Drosophila melanogaster) as a model organism to determine the epigenetic effects of 0.1% and 1% (w/v) curcumin, which have been shown to promote the health and prolong the lifespan of fruit flies. Both concentrations were found to significantly increase lifespan and climbing activity in male and female flies, but changes in HAT/HDAC gene expression and metabolism were sex-specific. Unexpectedly, the F1 offspring of curcumin-treated parental flies showed a significant reduction in lifespan that was also sex-specific, as well as sex-specific and dose-dependent transgenerational changes in HAT/HDAC gene expression and metabolism. These results show that curcumin's beneficial effects in the parental generation are followed by deleterious effects in the offspring, highlighting the need to further investigate the potential transgenerational effects of nutrients and bioactive compounds that are used as dietary supplements for humans.

Keywords: Drosophila melanogaster; aging; curcumin; epigenetics; nutrition; sex‐specific; transgenerational.

FIGURE 1

Curcumin increases food intake and enhances median lifespan in fruit flies. Food intake and body weight were measured after 5 days of treatment. (A) Food intake was not significantly changed by curcumin treatment in male flies, but female flies treated with 0.1% curcumin showed an increased food intake. (B) No significant changes in body weight were observed after 5 days. (C) Treatment with curcumin increased median lifespan in male and female flies. Boxplots in (A) and (B) show median, minimum, and maximum values. Lifespan is represented as Kaplan–Meier curves. Data represent three independent experiments, each with three replicates. (A) Kruskal–Wallis (B) ANOVA or Kruskal‐Wallis (C) Log‐rank Test (***p < 0.001). CUR, curcumin.

FIGURE 2

Curcumin increases the climbing ability of flies while reducing their overall activity. (A) Climbing ability is enhanced in male flies after 20 days of treatment with 0.1% curcumin and is still visible after 30 days. Female flies show enhanced climbing ability after 30 days of treatment with 1% curcumin. (B) Graphic representation of activity levels, which differ between male and female flies and are reduced by curcumin treatment in both sexes. Activity values are listed in Table 3. The boxplots in panel A show median, minimum, and maximum values. Data represent three independent experiments, each with three replicates. (A) Mixed model analysis (*p > 0.05; **p > 0.01). CUR, curcumin.

FIGURE 3

Changes in metabolism and gene expression after curcumin treatment after 8 and 30 days of treatment. Total levels of glucose, protein, and triacylglycerol (TAG), and the expression levels were analyzed after 8 and 30 days of treatment. (A) Total levels of glucose, protein, and TAG after 8 days show increased protein levels in female flies. (B) Total levels of glucose, protein, and TAG after 30 days show increased protein and TAG levels in male flies fed on 0.1% curcumin. (C) Expression levels of selected HAT and HDAC genes after 8 days show a reduction of enok expression in male flies and a reduction of Tip60, HAT1, Rpd3, and Sirt2 expression in female flies fed on 0.1% curcumin, as well as lower Sirt2 expression in flies fed on 1% curcumin. (D) Expression levels of selected HAT and HDAC genes after 30 days show increased levels of HAT1 expression in male flies. Boxplots show median, minimum, and maximum values. Data represent three independent experiments, each with three replicates. (A) ANOVA (B) ANOVA or Welch‐ANOVA (C and D) ANOVA or Welch‐ANOVA or Kruskal–Wallis (*p > 0.05; **p < 0.01; ***p < 0.001). CUR, curcumin.

FIGURE 4

Parental feeding with curcumin influences lifespan, metabolism, and gene expression in F1 offspring. (A) Lifespan curves show a shorter median lifespan in the offspring of curcumin‐fed parents, but the effects are dependent on sex and curcumin concentration. (B) Glucose, protein, and TAG levels in F1 offspring were measured after 30 days on the control diet. Protein levels were higher in female offspring of mothers fed on 1% curcumin. (C) Climbing ability of F1 offspring was measured after 10, 20, and 30 days on the control diet and was not affected by parental curcumin feeding. (D) Expression levels of selected HAT and HDAC genes in the F1 offspring were measured after 30 days on the control diet. Only male offspring showed alterations in gene expression, caused by either maternal (♀F0, HDAC4 upregulation) or paternal (♂F0, ATAC2 downregulation) feeding with curcumin. ♂F0: paternal feeding; ♀F0: maternal feeding. The boxplots in panels (B–D) show median, minimum, and maximum values, and lifespan is shown as Kaplan–Meier curves. Three independent experiments, each with three replicates, were performed. Data represent three independent experiments, each with three replicates. (A) Log‐rank Test (B and D) ANOVA or Welch‐ANOVA or Kruskal–Wallis (C) Mixed model analysis (*p < 0.05; **p < 0.01; ***p < 0.001). CUR, curcumin.