Why does the body need to sleep? We spend roughly one-third of our lives sleeping, but what purpose does it serve? Scientists know that sleep is necessary for overall health and brain functionality, but the process by which sleep delivers these health benefits is still unknown. Researchers from the University of Lausanne and the SIB Swiss Institute of Bioinformatics have recently been tackling new and unbiased approaches to breakdown sleep on a systems level.
One approach is “system genetics,” in which inferences about biological phenomena are made by connecting information about phenotype (our physical traits) with DNA (the code for these traits) through gene expression, proteins, and metabolism at the population level. Systems genetics is considered to be a critical part of predicting disease susceptibility due to its ability to interconnect biological phenomena on a global level.
The researchers performed system genetics analysis in mice in order to identify the molecular signaling pathways that predict susceptibility or resilience to sleep loss. Over seven years, the researchers created an open access and interactive knowledge base that quantifies the effects of sleep deprivation. This quantification is of the genome at the level of the brain and liver transcriptome, of the blood metabolome, and of the sleep-wake phenome referring to a detailed dissection of brain activity and sleep-wake behavior.
The study revealed a number of groundbreaking insights. Researchers found that preventing sleep during the first half of the habitual rest phase affected all systems levels with 78 percent of all expressed genes in the brain changing their expression. Furthermore, it was found that many genetic variants only exerted their action after the sleep deprivation challenge. These variants not only determined the magnitude of the molecular or sleep response to sleep loss, but in some cases also determined the direction of the change. This gives insight into the variance between individuals in their ability to cope with lack of sleep.
One of the major observations to come out of the study was that molecules and metabolic pathways active in peripheral tissue only (the liver) may directly influence phenotypes believed to be strictly central, such as the frequency of oscillations know to come from specific areas of the brain. Researchers also found evidence from all four levels of organization that implicated fatty acid metabolism as the substrate of the negative consequences of sleep loss.
These findings challenge the brain-centric view of sleep that has dominated the scientific community in the past, and may lead to new therapeutic strategies for sleep disorders.