Intestinal Overexpression of Circadian Clock Genes Modulates Lifespan and Thermotolerance in Male Drosophila melanogaster

Abstract This study investigates how overexpression of circadian clock genes affects longevity and stress resistance in male Drosophila melanogaster. Through analysis of transgenic strains containing UAS-controlled cryptochrome (cry) and period (per) genes with gut-specific GAL4 driver, we demonstrate that circadian gene overexpression produces temporally dependent physiological outcomes. Chronic overexpression throughout lifespan resulted in reduced median lifespan by 9–17% for cryptochrome genes and 4% for period genes (p < 0.05), while transient activation in young-imago ages of cry12, cry24, and per2.4 enhanced thermotolerance, increasing median survival under hyperthermic conditions by 18–25% (p < 0.05). These findings demonstrate that circadian genes act as bidirectional regulators of organismal physiology. The duration of overactivation determines whether the effects are beneficial or detrimental. Future studies are needed to distinguish the effects of stress tolerance from the costs of lifespan in order to enhance stress resistance without compromising longevity.