Abstract
Intermittent fasting (IF) has attracted significant interest as a potential approach with promising health benefits, including lifespan extension and metabolic improvement. Previous studies have shown that IF influences autophagy, metabolism, and oxidative stress across various organisms. Drosophila melanogaster was used in this study due to its genetic structure and metabolic responses that closely resemble those of humans, making it a valuable model for studying the effects of IF on cellular and molecular mechanisms. This study investigates the effects of IF on survival and the expression of genes related to autophagy, metabolic, and endogenous antioxidants in D. melanogaster to elucidate the molecular mechanisms underlying these effects. Male w (1118) flies were subjected to either a 4-h or 8-h fasting protocol, three times per week. The results revealed that both fasting protocols improved the survival of flies, with the 8-h IF group showing the most significant benefit (over 60% survival at day 10 compared to ∼50% in the control). Gene expression analysis demonstrated a significant downregulation in the fasting groups, with dilp2 decreasing by 45%, tom40 by 40%, cat by 50%, srl by 35%, and atg8a by 48%, indicating reduced insulin signaling, altered mitochondrial function, decreased antioxidant defense, and suppressed autophagy-related pathways. Notably, these findings contrast with previous studies reporting upregulation of autophagy and antioxidant responses during fasting, suggesting context-dependent regulatory mechanisms. Given the genetic and physiological similarities between D. melanogaster and mammals, these results provide insights into IF-induced metabolic adaptations and their potential implications for longevity and cellular homeostasis. Further research is warranted to clarify the molecular pathways involved.