AUTHOR=Williams Michael J., Perland Emelie, Eriksson Mikaela M., Carlsson Josef, Erlandsson Daniel, Laan Loora, Mahebali Tabusi, Potter Ella, Frediksson Robert, Benedict Christian, Schiƶth Helgi B. TITLE=Recurrent Sleep Fragmentation Induces Insulin and Neuroprotective Mechanisms in Middle-Aged Flies JOURNAL=Frontiers in Aging Neuroscience VOLUME=8 YEAR=2016 URL=https://www.frontiersin.org/articles/10.3389/fnagi.2016.00180 DOI=10.3389/fnagi.2016.00180 ISSN=1663-4365 ABSTRACT=Lack of quality sleep increases central nervous system oxidative stress and impairs removal of neurotoxic soluble metabolites from brain parenchyma. During aging poor sleep quality, caused by sleep fragmentation, increases central nervous system cellular stress. Currently, it is not known how organisms offset age-related cytotoxic metabolite increases in order to safeguard neuronal survival. Furthermore, it is not understood how age and sleep fragmentation interact to affect oxidative stress protection pathways. We demonstrate sleep fragmentation increases systems that protect against oxidative damage and neuroprotective endoplasmic reticulum molecular chaperones, as well as neuronal insulin and dopaminergic expression in middle-aged Drosophila males. Interestingly, even after sleep recovery the expression of these genes was still upregulated in middle-aged flies. Finally, sleep fragmentation generates higher levels of reactive oxygen species (ROS) in middle-aged flies and after sleep recovery these levels remain significantly higher than in young flies. The fact that neuroprotective pathways remain upregulated in middle-aged flies beyond sleep fragmentation suggests it might represent a strong stressor for the brain during later life.