For hundreds of years, scientists assumed that only the dose made the poison, and that more was always worse. Scientists also paid scant or no attention to the timing of the dose.

Today, we know better. We know that for some substances, less is more – that is, a lower dose will or can cause more harm than a large dose – this rule seems to apply especially to endocrine disrupters. We also know that the timing of the dose matters – think thalidomide and children with malformed or missing arms and legs if their mothers took thalidomide early in a pregnancy, as described in a 2009 paper from the Proceedings of the National Academy of Science

ScienceDaily now brings a new example of why timing matters. In a new paper in Nature, from scientists at Salk Labs, they’ve shown some small part of the biology behind why timing of a dose matters in terms of receiving a dose during sleeping and non-sleeping hours. The Salk press release includes the following key excerpts: 

In a paper published last week in Nature, scientists at the Salk Institute for Biological Studies report finding that proteins that control the body’s biological rhythms, known as cryptochromes, also interact with metabolic switches that are targeted by certain anti-inflammatory drugs.

The finding suggests that side effects of current drugs might be avoided by considering patients’ biological rhythms when administering drugs, or by developing new drugs that target the cryptochromes.

"We knew that our sleep and wake cycle are tied to when our bodies process nutrients, but how this happened at the genetic and molecular level was a complete mystery," says Ronald M. Evans, a professor in Salk’s Gene Expression Laboratory, who led the research team. "Now we’ve found the link between these two important systems, which could serve as a model for how other cellular processes are linked and could hold promise for better therapies."

For more information:

Nature

Authors: Katja A. Lamia, Stephanie J. Papp, Ruth T. Yu, Grant D. Barish, N. Henriette Uhlenhaut, Johan W. Jonker, Michael Downes, Ronald M. Evans

Cryptochromes mediate rhythmic repression of the glucocorticoid receptor