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PER, the Alarm Clock Gene

Many people, but particularly those who stick to a pretty regular schedule when it comes to the time that they’re going to sleep and the time that they’re waking up, have taken note of the fact that they frequently wake up on their own, before the alarm clock that they’ve set for themselves has the chance to sound.  Though they freely acknowledge that they’d rather wake up peacefully on their own rather than to the jarring sound of a buzzer or even music awakening them expectedly, they still find themselves wondering why this is happening. Now scientists have determined exactly how and why this happens.

Sleep scientists have discovered that buried deep within the brain there exists a clump of nerve cells known as the suprachiasmatic nucleus, and it is responsible for the body’s internal alarm clock. This wake/sleep computer is better known as the circadian rhythm, and it is what tells your body to start relaxing and feeling sleepy at bedtime and what makes you feel alert during the day. Circadian rhythm has a hand in the varying levels of your body’s blood pressure as it shifts throughout the day, the base body temperature, and your internal clock as well. And sleep researchers have found out that the body loves predictable behavior such as established sleep schedules and waking schedules, and responds to them by regulating itself to match. In fact, studies have shown that the more regular your schedule is, the more efficiently your body runs.

This predictable automatic sleeping/waking schedule that the body establishes in response to the schedule you establish for yourself is controlled by a protein known as PER. The levels of PER increase and decrease throughout the day, rising to its highest levels when it’s time for you to go to sleep and then dropping to its lowest levels throughout the night while you’re sleeping, preparing you for awakening with energy the next morning.

The discovery of the PER gene came at the hands of researchers at the Salk Institute for Biological Studies. Though the genetic propensity for having a gene that sets an internal alarm clock is interesting to those who are fortunate enough to benefit from its activities, it is even more interesting to those sleep researchers who are searching for a way to assist those who struggle with insomnia. According to Satchindananda Panda, an associate professor at Salk’s Regulatory Biology Laboratory, “The body is essentially a collection of clocks. We roughly knew what mechanism told the clock to wind down at night, but we didn’t know what activated us again in the morning. Now that we’ve found it, we can explore more deeply how our biological clocks malfunction as we get older and develop chronic illness.”

The Salk researchers collaborated with colleagues from McGill University and Albert Einstein College of Medicine. The group discovered that the gene KDM5A acts to encode the protein JARId1a, which switches on the biochemical action that instructs each of our circadian rhythms.  This discovery solves a mystery that had previously existed in what happened between our schedules and our bodies. The activity is controlled by PERIODIC, shortened to PER. When PER reaches its highest levels at night, it acts to stop two other proteins known as CLOCK and BMAL that are responsible for creating the high levels of PER in the first place. This means that PER actually acts to stop its own creation, thus allowing us to fall asleep easily at night.

The research that revealed the interactions between PER, CLOCK and BMAL was funded by Salk’s Innovation Fund, and allowed the researchers to find the enzyme that cause the body to wake up during the day. Determining that there is a genetic role in the production of these enzymes and proteins lead researchers to genetically modify the proteins to see what the impact would be.  Doing so stopped the PER protein from rising to its normal level and therefore made the lab animals that were being tested lose track of time. They then reinserted the genetically driven protein and found that the animals were able to return to a normal sleep cycle.

With their new understanding of the interplay between genes and the proteins and enzymes that act to makes us wake up and feel sleepy, researchers are looking to a future that will enable them to consider new drugs that target the production of these proteins in order to treat sleep disorders.  It can also play a role in the treatment of a number of chronic diseases that are particularly linked to sleep deprivation. It may also be helpful in treating older people, who notoriously lose their sense of time when it comes to sleep and waking, as well as in assisting those who do shift work.

What is most interesting to the average person (rather than sleep researchers) is the fact that the body appears to learn the sleep routine that you establish. The levels of PER increase based upon the time that you go to bed each night, and decrease based upon the time that you set your alarm for each morning. It appears that the body wants to wake up before the alarm clock goes off, almost as though it prefers to wake itself up rather than experience the jarring impact of the alarm. Many people repot waking up a matter of minutes, and even seconds before the time that the alarm is set for.

Other studies have shown that the body preps itself for a wake up time. One famous study conducted at the University of Lubeck in Germany involved fifteen participants who were told that they would be awakened at 6 a.m. on some nights and at 9 am on others. What was discovered was that when sleepers were told they’d be awakened at 6, their stress hormone levels increased at 4:30 a.m. in anticipation of being woken up, but when they were told they’d be awakened at 9 a.m. and then woken earlier, the hormone levels were so low that they were drowsy for hous.

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