A study revealed the relationship between sleep deprivation and death.
The significance of sleep for survival is underscored by observable behavioral patterns, the presence of sleep-like states in primitive organisms, and the fact that severe sleep deprivation can lead to fatality. However, the exact cause behind one of these fatal outcomes has remained elusive.
On June 4, 2020, Dragana Rogulja's team at Harvard Medical School published a groundbreaking research paper titled "Sleep Loss Can Cause Death through Accumulation of Reactive Oxygen Species in the Gut" in Cell, demonstrating that sleep deprivation prompts the buildup of reactive oxygen species (ROS) and subsequent oxidative stress, particularly within the gut.
Reactive oxygen species aren't just linked to sleep deprivation. They also drive the process of death itself. Counteracting their effects mitigates oxidative stress, allowing Drosophila to maintain a normal lifespan even with minimal or no sleep. This is achieved through the administration of antioxidant compounds or the introduction of gut-targeted antioxidant enzymes. Hence, the demise resulting from severe sleep deprivation may indeed be attributed to oxidative stress, with the gut emerging as a pivotal player in this intricate process. Survival in the absence of sleep becomes viable when the accumulation of ROS is averted.
Sleep, an encompassing state rendering animals inert and unresponsive, isn't easily encapsulated by a singular function. Rather, it influences various processes such as cognition, immunity, and metabolism. Innumerable clinical and experimental studies have underscored the connection between sleep deprivation and severe health issues. The restriction of sleep can even precipitate early mortality in model organisms like dogs, rats, cockroaches, and fruit flies.
Traditionally, sleep's neurological basis has led to the assumption that death stemming from sleep deprivation is rooted in impaired brain function. This view is supported by the evident cognitive decline following sleep deprivation. The restoration of brain function post-sleep is attributed to two primary processes—synapse size reduction, and the removal of detrimental substances from cerebral mesenchymal regions. However, it remains unclear how these processes relate to the lethality resulting from sleep deprivation, as inducing them during wakefulness or inhibiting them during sleep proves challenging. Beyond cognitive impairments, sleep deprivation also disrupts gastrointestinal, immune, metabolic, and circulatory functions. Whether these disruptions are secondary to neurological changes or direct, independent consequences of sleep deprivation remains uncertain.
One proposed function of sleep is to forestall oxidative stress in the brain. Multiple studies have indicated that sleep deprivation alters antioxidant responses within the brain. Recent findings even highlight how sleep deprivation influences the redox state of various sleep-regulated neurons in the Drosophila brain, thereby affecting their activity. While the brain seems relatively unscathed by sleep deprivation, some research avenues are exploring oxidative stress indicators elsewhere. For instance, rodents subjected to prolonged sleep restriction display diminished endogenous liver antioxidant defenses, accompanied by organ oxidation. However, the localized source of oxidized molecules during sleep deprivation remains elusive, obscuring the relationship between oxidation and sleep-deprived animal mortality.
To identify direct links between sleep deprivation and mortality, researchers adopted an agnostic approach, scrutinizing multiple tissues concurrently. Initial investigations were conducted on Drosophila as a model, chosen due to shared sleep attributes with mammals and the essential role of sleep in the natural lifespan of Drosophila. Upon pinpointing the timeframe required for sleep deprivation-induced death, researchers examined various cellular damage markers preceding this point. Remarkably, ROS, volatile and reactive molecules, emerged as the catalyst for cellular damage and subsequent lethality during sleep deprivation. While endogenous ROS serve as vital signaling agents, their accumulation beyond cellular antioxidant capacities triggers cascades of oxidation reactions. Reactive oxygen species, owing to their unpaired valence electrons, actively interact with macromolecules (DNA, proteins, and lipids), destabilizing them by stripping electrons.
Three distinct methods of sleep deprivation yielded ROS buildup in the gut of Drosophila, precipitating oxidative stress within this organ. Following the cessation of deprivation, ROS levels and oxidative stress markers gradually receded. Correspondingly, sleep-deprived mice showcased similar results, with ROS concentration predominantly escalating in the small and large intestines, thereby inducing oxidative stress. Notably, a causal link between accumulated reactive oxygen species and diminished survival was established in Drosophila. The scavenging of ROS from the gut, achieved through oral administration of antioxidant compounds or the introduction of gut-targeted antioxidant enzymes, enabled Drosophila to sustain a regular lifespan despite minimal or no sleep. Consequently, the study posits that sleep deprivation has implications for human longevity and that the administration of antioxidants to alleviate ROS accumulation in the gut holds promise for rescuing individuals, without necessitating an increase in sleep duration.