Circadian Cycles

Circadian Cycles

The New England Journal of Medicine recently had a review article on circadian mechanisms.  What was once thought to simply control sleep/wake periodicity and females’ monthly cycles is now known to control our complex physiology even down to a cellular level.  Also, they are not unique to humans but have been present in all life forms (plant and animal) for the past 3 billion years. 

This universal presence indicates that circadian cycles are critical for both fitness and survival of all species. 

In humans there are two types of circadian clocks: the master clock in the brain and individual clocks in individual cells.  In the brain, the main timepiece is found in an area comprised of about 20,000 nerve cells called the suprachiasmatic nucleus (SCN).  But, the key input to this area comes from our eyes via photo receptor cones and rods.  The input of light sets the pacemaker cells in the SCN to our specific cycle.  These pacemakers can only reset themselves by one hour per day.    Thus, travel across multiple time zones requires one day for each zone crossed to reset.  This is called jet lag.  But many people experience a similar disruption due to “social jet lag” which occurs when sleep time varies a lot due to work/school hours versus weekends. 

Another source of disruption occurs due to the frequent use of electronic devices such as computers and smart phones.  The blue light emitted by electronics has a very strong clock resetting effect. 

Individual cells contain clock genes referred to as CLOCK-BAMAL1 that regulate DNA, RNA and protein synthesis.  By so doing, cells will perform best at certain times of the day and poorly at other times.  This has important ramifications for our immune systems and allergy.  It has

been shown that allergic reactions are more likely to be severe when there is a dysregulated clock. 

Immune defense against infection can be similarly impaired. Inflammatory diseases such as inflammatory bowel disease and arthritis worsen with clock dysfunction.  Even immune protection against cancer is reduced in shift workers and in people with frequent alterations in circadian cycles.  This has been very clearly shown for breast cancer, colon cancer and prostate cancer.  Curiously, exposure to artificial light at night increases the risk for melanomas, independent of degree of sun exposure.  Also, morning sunlight is more likely to promote skin cancer development than sunlight later in the day.

So, I guess Tom Hank’s character Chuck Noland said it best in the movie Castaway: “We live and we die by time and we must not commit the sin of turning our back on time.” 

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