California researchers have gained fresh new insight into the factors that influence our internal clocks and say their findings could lead to new treatments for metabolic disorders such as obesity and diabetes.
“Our group has been fascinated with circadian rhythms for over 10 years now, as they represent a marvelous example of robust control at the molecular scale in nature,” said Frank Doyle, chair of University of California, Santa Barbara’s Department of Chemical Engineering and the principal investigator for the UCSB team. “We are constantly amazed by the mechanisms that nature uses to control these clocks, and we seek to unravel their principles for engineering applications as well as shed light on the underlying cellular mechanisms for medical purposes.”
All living creatures have their own built-in biological clock which produces oscillations in a roughly 24-hour cycle that regulate various physiological and behavioral tasks. In humans, this complex body clock helps time and control many of our bodily functions such as eating, sleeping, body temperature, blood pressure and the production of certain hormones that regulate various internal organs.
Our blood pressure for example, doesn’t remain constant; it rises and falls depending on the time of day or night. Our senses, such as sight, smell and taste, are also controlled by our circadian rhythm. Our physical lives in essence are run by the beat of our internal clock.
“These oscillations are caused by genetic circuits. So you’ll have a gene that’s produced, and when it’s in its finished form, it will turn itself off,” said Peter St. John, lead author of the study and a researcher in UCSB’s Department of Chemical Engineering. He added that the proteins and genes that produce the daily oscillations clear out when they’ve done their jobs, allowing the body to restart the process of producing these materials once again. All of this takes place within a cycle that takes roughly 24 hours to complete.
A person’s genetics do play a part in these rhythms, according to the researchers. For example, if your parents were night people, there’s a good chance that you will be too. But other factors, such as environment, daily habits and lifestyle, also affect our internal clock.
“It’s not just this free-running oscillator,” said St. John. “It gets these inputs from light. For instance, if you get light early in the morning, it’ll speed up something so your phase is adjusted to the time of day.”
St. John also pointed out other influences that can adjust a person’s circadian rhythm are those such as the time they eat, the kind of drugs they take, whether they have a work schedule that involves varied shift times, or if they take trips that often take them across time zones.
The researchers found that our bodies can get into trouble whenever our internal clock is thrown off-kilter due to these factors. This is also known as having a low-amplitude rhythm.
This low-amplitude rhythm can have an impact on necessary cellular activity that is supposed to take place at certain times of the day or night.
The researchers said these disruptions to our internal clock could lead to ailments like diabetes, heart disease and obesity. Looking at some very basic research, it has also been found that these low-amplitude rhythms have also been linked with diseases such as Alzheimer’s as well as certain liver conditions.
The research team looked at proteins called Period (PER) and Cryptochrome (CRY) that help regulate and control our circadian clocks and developed models that demonstrated how two small-molecule drugs, Longdaysin and KL0001, impacted these proteins.
They felt the insight into the mechanisms behind the metabolic aspects of circadian rhythms that they gained could lead to therapies to decrease the risk of diseases that are associated with disrupted rhythms.
The researchers, who outlined their findings in in the early edition of the Proceedings of the National Academy of Sciences, plan to continue their research in this area.
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