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Chronic sleep curtailment expediates brain aging by activating the complement and coagulation cascades in mice

Jha, P. K.; Valekunja, U. K.; Reddy, A. B.

2025-02-23 neuroscience
10.1101/2025.02.18.638886 bioRxiv
Show abstract

Chronic sleep insufficiency is prevalent in modern society and has been associated with age-related neurodegenerative diseases. Loss of sleep accelerates the progression of neurodegeneration in animal models of neurological diseases. Here, we study whether chronic sleep curtailment leads to brain aging in wild-type animals without a genetic predisposition. We used a wild-type mouse model to simulate 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 149 proteins related to sleep and 1269 related to age with 96 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), alpha-2-macroglobulin (A2M), fibrinogen alfa and beta chain (FGA and FGB). This is the first study indicating the possible role of the complement and coagulation pathways in brain aging and by chronic sleep restriction (CSR) in mice.

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