Researchers from the University of Pennsylvania have found our daily rhythms of sleep and wakefulness have a more profound effect on our bodies than previously thought — and point to a way to make medications more effective.
The body’s internal clock is well known to control things such as body temperature and heart rate. But to reveal the full extent of clock control, senior author John Hogenesch, a Penn professor of pharmacology, said his team looked at the activity of thousands of genes in mice over the course of a day.
Looking in 12 different tissues in the largest study of its kind, they found 43 percent of protein-coding genes were expressed in 24-hour cycles. The results were published in the journal PNAS.
Most of the activity in a given organ was concentrated before dawn or dusk in a kind of morning or evening “rush hour.”
“They got really interesting because they weren’t the same for each organ,” said Hogenesch. “For example, the liver had a rush hour anticipating the dawn, whereas the lung had a rush hour anticipating the dusk.”
The team also found that 56 of the top 100 bestselling drugs in the U.S. target one of those cycling genes, which has huge implications for how people should take medications.
“Something like 90 percent of [those drugs] have never been evaluated for when you take them at time A vs. time B,” said Hogenesch. “So I think there’s a great deal of opportunity here to take our already efficacious, relatively safe and effective drugs and make them work better.”
One of the rare drugs that has been studied — a blood pressure-lowering medication — works 60 percent better if taken at bedtime rather than in the morning.
Based on their results, Hogenesch said it now makes a lot of sense to begin focusing on dosing time in clinical trials, especially because the cost of new drug development is so high.
From the mouse data, the team already has a sizable list of medications worth investigating.