One week of poor sleep can disrupt hundreds of genes linked to stress, immunity and inflammation, research has shown.
Scientists think the discovery could explain why lack of sleep can have a devastating impact on health.
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 "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 researchers believe their findings may be particularly relevant to people working long hours in industrialised societies.
The scientists, led by University of Surrey sleep expert Professor Derk-Jan Dijk, analysed RNA - the messenger chemical that delivers coded "instructions" from the genes to cells - in the blood of volunteers.
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 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, samples were taken when volunteers stayed awake for a long period at the end of the study.
The scientists noted: "Sleep obtained in the sleep-restriction condition was not sufficient to maintain alertness or performance."
Meanwhile, a new study has found two out of five office staff are working under "dangerously high" stress levels.
A survey of 2,000 workers from private companies as well as the NHS and police, revealed that stress at work affected their health.
Just over half those studied said they worked more than 10 hours unpaid overtime every week.
Neil Shah, who conducted tests on hundreds of workers as part of the study, said: "This research shows that many people in the UK today are working under some dangerous levels of stress - they may not even be aware of how stressed they are."
The research, by office supplies firm Viking , showed that some employees such as teachers, blamed incompetent colleagues for stress.