Sleep deprivation and aging are metabolically linked across tissues

Abstract Study objectives Insufficient sleep is a concerning hallmark of modern society because sleep deprivation (SD) is a risk factor for neurodegenerative and cardiometabolic disorders. SD imparts an aging-like effect on learning and memory, although little is known about possible common molecular underpinnings of SD and aging. Here, we examine this question by profiling metabolic features across different tissues after acute SD in young adult and aged mice. Methods Young adult and aged mice were subjected to acute SD for 5 hours. Blood plasma, hippocampus, and liver samples were subjected to UPLC-MS/MS-based metabolic profiling. Results SD preferentially impacts peripheral plasma and liver profiles (e.g. ketone body metabolism) whereas the hippocampus is more impacted by aging. We further demonstrate that aged animals exhibit SD-like metabolic features at baseline. Hepatic alterations include parallel changes in nicotinamide metabolism between aging and SD in young animals. Overall, metabolism in young adult animals is more impacted by SD, which in turn induces aging-like features. A set of nine metabolites was classified (79% correct) based on age and sleep status across all four groups. Conclusions Our metabolic observations demonstrate striking parallels to previous observations in studies of learning and memory and define a molecular metabolic signature of sleep loss and aging. Graphical Abstract