Prenatal hyperbaric normoxia treatment improves healthspan and regulates chitin metabolic genes in Drosophila melanogaster

Aging is a universal, irreversible process accompanied by physiological declines that culminate in death. Rapid progress in gerontology research has revealed that aging can be slowed through mild stress-induced hormesis. We previously reported that hyperbaric normoxia (HN, 2 atm absolute pressure with 10% O₂) induces a cytoprotective response in vitro by regulating fibronectin. In the present study, we investigated the hormetic effects of prenatal HN exposure on Drosophila healthspan related to molecular defense mechanisms. HN exposure had no disruptive effect on developmental rate or adult body weight. However, lifespan was clearly enhanced, as was resistance to oxidative and heat stress. In addition, levels of reactive oxygen species were significantly decreased and motor performance was increased. HN stress has been shown to trigger molecular changes in the heat shock response and ROS scavenging system, including hsp70, catalase, glutathione synthase, and MnSOD. Furthermore, to determine the hormetic mechanism underlying these phenotypic and molecular changes, we performed a genome-wide profiling in HN-exposed and control flies. Genes encoding chitin metabolism were highly up-regulated, which could possibly serve to scavenge free radicals. These results identify prenatal HN exposure as a potential hormetic factor that may improve longevity and healthspan by enhancing defense mechanisms in Drosophila.