Unstable molecules in the gut implicated in early death from sleep deprivation
An underlying cause for early death associated with sleep deprivation may be because of accumulation of a type of oxygen-based molecule in the gut. Scientists at Harvard Medical School (HMS) in Massachusetts, US, have studied trusty models of the fruit fly only to find that sleep-deprived flies had a strong buildup of molecules known as reactive oxygen species (ROS) which can cause cell death by damaging DNA and other important cellular components. Cell death will eventually bring about death of the host, in this case, humans.
Fruit flies share similar genetic make-up with humans, including genes that regulate sleep – some flies in this experiment were genetically manipulated to express proteins that suppress sleep at warmer temperatures. After 10 days of heat-induced sleep deprivation, mortality began to take off and all of the fruit flies were deadby around day 20. The control group undera normal sleep cycle instead lived for around 40 days.
When seen under a microscope, most of the tissues between the sleep-deprived and healthy flies were indistinguishable in terms of cell damage. The HMS scientists, however, did notice ROS buildup in the gut of the sleep-deprived group; their numbers peaked after around 10 days of sleep deprivation, coincidentally as mortality began to increase.
Interestingly, when the sleep deprivation was ended and the flies experienced regular sleeping patterns, the ROS levels began to decline. To further understand how the molecules might play a causal role in early death, the team treated the flies with antioxidant compounds that neutralised/cleared out ROS from the gut, and also genetically manipulated flies to overproduce antioxidant enzymes in the gut. These groups of flies were observed to have normal or near-normal lifespans, despite being subjected to sleep deprivation.
“We found that premature death could be prevented,” said Dragana Rogulja, Professor of neurobiology at HMS.“Each morning, the team would all gather around to look at the flies, with disbelief to be honest. What we saw is that every time we could neutralise ROS in the gut, we could rescue the flies.”
Experiments in mice were much the same – the scientists observed elevated ROS levels in the intestines of mice, compared to a control group, after subjecting the rodents to a form of mechanical stimulation to keep them awake for five days.
Although the scientists are yet unsure“why sleep loss causes ROS accumulation in the gut, or why it is lethal,” they hope the initial discovery can guide treatments that counter the effects of sleep deprivation in humans.
