The role of sleep disorders in orchestrating proteomic dysfunction and multi-morbidity

Sleep integrity has been recognized as a crucial contributor to maintain health and cellular homeostasis. Current evidence supports a bidirectional relationship between sleep disorders and different molecular mechanisms such as protein homeostasis (proteostasis). Nevertheless, few studies have been performed to understand the relation between proteostasis network (PN), sleep disorders and the development of age-related diseases. Hence, in this review we focus on describing the effect of sleep disorders over proteostasis defined as the dynamic balance of protein synthesis, folding, trafficking, and degradation essential for maintaining cellular functions. First, we synthesize emerging evidence about dysfunction of the PN and sleep disorders -including insomnia, sleep-disordered breathing and circadian misalignment. Then, we discuss a conceptual framework in which sleep disruption and the concomitantly PN imbalance leads to many chronic diseases including neurodegenerative, metabolic, cardiovascular, breathing disorders, cancer, cataracts, and sarcopenia. Finally, we suggest that sleep disturbances act as an active modifier of PN that may influence susceptibility to many age-related diseases, and emphasize the need of longitudinal human studies to define the temporal and mechanistic relationships within the sleep-proteostasis-aging axis.