Rest, Repair, Repeat: The Complex Relationship of Autophagy and Sleep

Autophagy and sleep are two evolutionary conserved mechanisms across the animal kingdom. Autophagy is a pathway for the degradation of cytoplasmic material in the lysosome, playing important roles in the homeostasis and health of the organism. On the other hand, sleep is a homeostatically regulated state with numerous presumed essential roles, including the restoration of tissue and physiological functions, such as brain waste clearance via the activation of the glymphatic systems. Given that sleep and autophagy are crucial processes tightly linked to homeostasis and maintenance of good health, understanding how they interact is of great interest, especially as sleep quality decreases in our modern 24-hour societies. Autophagy represents a promising target for therapeutic interventions in this context. Here, we review the contrasted and complementary roles of autophagy and sleep in maintaining homeostasis. Specifically, we focus on recent evidence suggesting that sleep impairment may increase autophagy, while autophagosome levels may modulate the amount of sleep. We discuss outstanding questions at the intersection of these two fields, highlighting methodological shortcomings in the current literature. Overcoming these limitations will be instrumental to design new experiments with the aim of answering one of the greatest mysteries of our time - why do we sleep?