Maternal Iron Deficiency Modulates Antioxidant Status and Longevity in a Sex-Dependent Manner in Drosophila melanogaster

Background : Maternal iron deficiency (ID) disrupts both maternal and offspring health by impairing iron status and antioxidant defenses. This study examines the intergenerational effects of maternal ID and rapamycin intervention on Drosophila melanogaster . Rapamycin is known for promoting autophagy, longevity, and antioxidant activity. Method : Female flies (F0) were subjected to an iron-deficient diet for 14 days, followed by a 30-day intervention with either a normal diet or a rapamycin-treated diet. After the iron chelation, some of the F0 females were crossed with normal males to produce F1 offspring. Physiological, biochemical, and gene expression changes were assessed in F0 flies after 14 days of iron chelation and 30 days of interventions. Post-eclosion evaluations were conducted for F1 flies, along with a 60-day survival study for both generations. Result : In F0 females, iron chelation significantly reduced (p < 0.0001) body weight, iron levels, and antioxidant enzyme levels, while increasing GSH levels. Gene expression showed significant changes (p < 0.05) in iron storage ( Fer1HCH ), autophagy ( ATG1 ), and telomere-related genes ( dHeT-A , dTahre , dTart ). A normal diet partially restored iron levels and survival, while the rapamycin-treated diet improved antioxidants but had mixed effects on survival and gene expression. F1 male/female offspring on a normal diet exhibited reduced/increased iron levels respectively, and also increased median survival in both offspring. Rapamycin increased body weight and iron levels in female offspring but reduced their median survival. Conclusion : Maternal ID has lasting effects, with normal diets restoring iron levels while rapamycin enhances antioxidant defenses and reduces survival, particularly in females.