One week of poor sleep can disrupt hundreds of genes linked to stress, immunity and inflammation, research has shown.
The discovery could explain why lack of sleep is so bad for the health.
Sleep deficiency is associated with a host of conditions including obesity, heart disease and mental impairment. But scientists are still trying to understand the molecular mechanisms involved.
For the new study, researchers examined gene activity in 26 sleep-deprived volunteers.
They found that insufficient sleep had an impact on more than 700 genes. Some had their activity dampened, while others became extra-active.
Those affected included genes associated with the circadian night and day "body clock" cycle, metabolism, and immune and stress responses.
Poor sleep also altered chromatin - the DNA and protein "packaging" that plays an important role in gene regulation.
The scientists, led by sleep expert Professor Derk-Jan Dijk, from the University of Surrey, wrote in the journal Proceedings of the National Academy of Sciences: "Biological processes affected included chromatin modification, gene-expression (activity) regulation, macro-molecular metabolism, and inflammatory, immune and stress responses.
"The identified biological processes may be involved with the negative effects of sleep loss on health, and highlight the inter-relatedness of sleep homeostasis (stability), circadian rhythmicity, and metabolism."
Prof Dijk's team analysed RNA - the messenger chemical that delivers coded "instructions" from the genes to cells - in the blood of volunteers. RNA can be used as a tool to measure gene activity.
Participants were exposed to a week of poor sleep during which they slept no more than six hours a night. At the end of this time, they had to stay awake for around 40 hours while RNA samples were collected at three hourly intervals.
The results were compared with the effect on the same volunteers of sleeping up to 10 hours a night for a week. Again, RNA samples were taken during a long period of wakefulness at the end of the study period.
During the "sleep-restriction condition" volunteers got an average of 5.70 hours sleep a night.
The scientists noted: "Sleep obtained in the sleep-restriction condition was not sufficient to maintain alertness or performance."
The findings may be relevant to many people living in industrialised societies, they said.
In the US, 30% of adults reported getting six hours sleep or less a night on average.