Chronic sleep restriction activates complement and coagulation cascades: a molecular link to accelerated brain aging

Chronic sleep insufficiency is prevalent in modern society and has been associated with age-related neurodegenerative diseases. Sleep loss accelerates neurodegeneration in animal models. Here, we study whether chronic sleep curtailment leads to brain aging in wild-type mice without a genetic predisposition. We simulated modern-day conditions of restricted sleep and compared the brain (cortex) proteome of young sleep-restricted animals with different aged control groups. We report the alteration of 145 proteins related to sleep and 1275 related to age, with 71 proteins common between them. Through pathway analysis of proteins common to sleep restriction and aging, we discovered that the complement and coagulation cascade pathways were enriched by alterations of complement component 3 (C3), fibrinogen alpha and beta chain (FGA and FGB). This is the first study indicating the possible role of the complement and coagulation pathways in brain aging by chronic sleep restriction (CSR) in mice.