Trex1 overexpression leads to longer lifespans and fragmented sleep in Drosophila melanogaster

Three-prime repair exonuclease 1 (Trex1) prevents cytosolic DNA accumulation and immune activation, yet the physiological consequences of increased Trex1 expression in vivo remain unclear. In this study, we used Drosophila melanogaster, a model well suited for quantitative analyses of aging, sleep, and circadian rhythms, to generate flies that ubiquitously overexpress murine Trex1 under the Act5C-GAL4 driver, given that a clear Trex1 ortholog has not been identified in flies. Trex1 overexpression significantly extended the lifespan of male flies (40.55 ± 1.10 days in controls; n = 60 vs. 44.98 ± 1.59 days in Trex1; n = 57, p < 0.05, Bonferroni corrected), whereas female flies showed a modest but statistically non-significant increase in lifespan. Interestingly, Trex1 overexpressing flies exhibited more fragmented sleep and reduced circadian rhythm robustness compared with controls. These findings suggest that the mechanisms by which Trex1 overexpression influences lifespan and those regulating sleep and circadian stability may be functionally separable.