Ogni volta che il nostro pianeta compie una rotazione di 24 h, alcuni aspetti della nostra chimica interna attraversano a loro volta dei cicli di cambiamento, influendo sul funzionamento di diverse parti del nostro organismo e divenendo oggetto di un intero campo di studi: la cronobiologia. Uno studio condotto dai ricercatori dell’Università della Pennsylvania, pubblicato sulla rivista “Proceedings of the National Academy of Sciences”, dimostra come i cicli circadiani possono influenzare anche gli effetti dati dall’assunzione di alcuni farmaci.

Every time our planet goes through its 24 hour rotation, aspects of your internal chemistry swing through cycles of change – in your brain, your liver, your heart and your fat cells. Timing is so important to living things that there’s a whole field – chronobiology – devoted to studying it.

Now, scientists are claiming that 56 of the 100 top selling drugs directly bind components of that day-night dance. The drugs include everything from Ritalin to Nexium, Viagra to forms of cancer chemotherapy. The implication, said lead researcher John Hogenesch, is that the time of day these drugs are taken may influence efficacy and potential for side effects.

The research, done at the University of Pennsylvania and published this week in the Proceedings of the National Academy of Sciences, used mice, but the researchers say it is relevant to humans because circadian clocks are so deeply rooted in life on Earth, affecting not just animals but plants, some fungi and even bacteria. Mice are somewhat reversed from humans, becoming active at night and sleeping in the day, but both species show profound changes over a 24-hour cycle, said Hogenesch. And we and mice use roughly the same molecular mechanisms for keeping time.

He said that while sunlight can reset our circadian clocks, our bodies also depend on internal timekeeping devices, or “endogenous clocks,” which keep many living things on a rhythmic schedule even when subject to 24 hours of light or of darkness. One active area of research is trying to understand how these internal clocks work, said Hogenesch.

“How do you get a biological clock out of proteins and lipids?” he said. “We know how we make a watch but we don’t really know how we make a biological clock.”

The University of Pennsylvania has long been a center for studying the influence of time on the living world, with much of the research using fruit flies. Like us, fruit flies need their sleep. Back in the 1990s, Penn scientists found that when they kept flies in perpetual darkness and monitored their activity with strategically placed motion sensors, they found the flies kept a regular schedule, suggesting they must have built-in clocks.

The first circadian rhythm gene, called “per” was found in flies by Seymour Benzer, a famous fly researcher at Caltech. Penn researcher Amita Sehgal and colleagues suspected there were others, and by inducing various mutations and testing the sleep schedule of their flies, they found a gene called “tim”.

Flies with damage to the tim gene didn’t sleep at all, which may sound appealing if not for the fact that these flies didn’t live long. The two genes, tim and per, seem to work together to create a chemically driven internal clock. The genes orchestrate the production of two proteins that bind together and accumulate, then disintegrate over a 24-hour cycle.

The research published this week focused on a different question – how these timing mechanisms influence the rest of an animal’s biology. Their approach was to look for cyclical patterns in the way the messages these genes hold get transcribed – how their recipes are turned into proteins. The researchers found that 43% of mouse genes showed activity patterns tied to the day-night cycle, with two physiological “rush hours” of high general activity before dawn and dusk.

Many of these genes showed cyclic behavior in some organs but not others, said Hogenesch. The scientists looked at adrenal glands, aorta, brain stem, brown fat, cerebellum, heart, hypothalamus, kidney, liver, lung, skeletal muscles, and white fat. The researchers also found circadian rhythm influenced parts of the so-called noncoding parts of the genome – the stretches of DNA that don’t make up genes […]

 

Leggi l’articolo completo su: http://www.forbes.com/sites/fayeflam/2014/10/27/new-research-shows-your-body-clock-may-influence-how-many-drugs-work/