Talk of Circadian Rhythm

Biology 103
2000 First Web Report
On Serendip

Talk of Circadian Rhythm

Susanna Jones

Humans are obsessed with time. High-tech watches, alarm clocks, and twentry-four hour commerce reflect humans' need to control and plan every minute of every day. However, the student who pulls an all-nighter, the traveller who crosses time zones, and the EMT working the night shift have all experienced the reprecussions of manipulating time. Why can't some of us wake up at four AM and start the day refreshed and energized? The answer to this question lies in the understanding of our "biological clock," a term which is now considered very crucial to many scientific disciplines. Scienitists in the growing field of chronobiology are devoted to studying the innerworkings of our biological clocks, a study which sheds light on an arrray of other subjects such as sleep cycles and disorders, medical treatments, genetics, and evolution.

Circadian Rhythm Identified

In 1729, French astronomer Jean Jacques d'Ortuous de Marian isolated plants that demonstrated daily leaf movements in dark rooms for several days. He found that even in the absence of sunlight, the plants continued to open their leaves during the day and close during the night. He concluded that the observed cycle was not a result of external forces (sun) but was an innate property of the plant. Here, the study of biological clocks began (1). The biological clock sets a daily rhythm, or cycle, which influences organisms' physiological functions and behaviors; this rhythm is called a circadian rhythm ("circa" means around and "dia" means day). All organisms have biological clocks, although they may vary greatly depending on the organism's activities (2).

The Structure of the Clock

To understand the biological clock, scientists must examine things at a molecular level. Are there molecules that are equivalent to the gears and springs of a watch? In 1994, two "clock genes" were identified in drosophila. From there, scientists found clock genes in humans, rodents, fish, frogs, insects, plants, and cyanobacteria (1). Today, the most extensive studies are conducted on mice and drosophila, whose clock genes function very similarly to humans'.

Ricki Lewis, author of several biology textbooks, explains the workings of the biological clock: "At the molecular level, a biological clock is a system of oscillating levels of proteins, controlled by transcription factors, which are proteins that turn particular genes on and off' (3). Without sunlight the clock will still run, however, the light of day plays an important role in regulating these proteins. Basically, during the day, proteins switch on certain clock genes, which in turn causes the genes to produce other proteins. At night, the buildup of proteins switches off the genes and ceases production (4). The levels of the proteins oscillate according to what time of the twenty-four hour day it is. Once the twenty-four hours is up, the cycle repeats itself.

For example, melatonin is a hormone that induces sleep. The system of clock cells adjusts itself so that when it is night, a greater amount of melatonin is released. When the seasons change, the clocks readjust themselves so that melatonin can be released at the proper time each night. Therefore sleep-wake cycles are largely influenced by clock cells (5). Clock cells also influence the rise and fall of an organism's internal temperature, blood pressure and eating habits throughout the day.

How do molecules know what time of day it is in the first place? Isaac Edery of Rutgers University explains: "Synchronization of circadian oscillators with the outside world is achieved because light (or other external temporal cues) has acute effects on the levels of one or more of a clock's components, the consequences of which have ripple effects that are experienced throughout the interconnected molecular loops, leading to a stable phase realignment of the endogenous rhythm generator and the external entraining conditions "(1). In other words, while light does not necessarily set the clock (as d'Ortuous de Marian demonstrated), it can affect the clock's functioning so that the internal structure of the clock can run parallel to the external environment.

Edery identifies three intrinsic characteristics of circadian clocks: 1) circadian rhythms can continue to run without environmental time cues (i.e. light), 2) circadian rhythms can be reset by changes in environmental conditions, and 3) the period of the circadian rhythm does not vary with the frequent changes of temperature in the environment (1).

The first characteristic again relates to the clock's ability to keep ticking in the absence of environmental time cues (i.e. the plants without sun). This feature may allow an animal to maintain the synchronicity between its circadian clock and the external environment in adverse weather conditions or when the animal must seek shelter for long periods of time (1).

The second characteristic, the ability to reset the circadian clock, enables us to maintain alignment with local time. Therefore, if someone travels to China from America, one can gradually acquaint herself to the foreign time and create a new rhythm (1).

The third characteristic addresses temperature and circadian rhythm. Regardless of whether the day is warm or cold, the cycle still lasts twenty-four hours. Therefore, a mechanism exists which offsets the effects of temperature changes so that the "clock" can accurately keep time (1).

Location of the "Clock"

Initially, scientists believed that the circadian clock of mammals was comprised of about 10,000 clock cells which resided in an area of the hypothalamus called the suprachiasmatic nucleus, or SCN (4). However, recent studies show that clock cells dwell in other tissues of the body as well. When morning light (a time indicator) hits the retina, the photic input is carried to the SCN and then transmitted to various other clock cells throughout the body. Edery explains the process: "The emerging picture is that...much of the photic input to the circadian timing system is transduced via the retinohypothalamic tract (RHT) to the SCN, which in turn conveys time-of-day information to peripheral clocks that have tissue-specific regulatory features" (1). Therefore, when external time cues change (i.e. time zones), not only must the clock cells of the SCN readjust, but the clock cells throughout the rest of the body must resynchronize as well. As a result, if someone is experiencing jet lag, she will probably exhibit symptoms other than just sleepiness, because her entire body is being affected by the change. This also applies to "night people" who when forced to wake up early may experience nausea or muscle fatigue.

Some Implications of a Researched "Biological Clock"

Evolution: Because researchers now believe that all living organisms (from bacteria to mammals) have biological clocks, it can be assumed that biological clocks are both "ancient and essential" (3). If biological clocks are widespread in evolution, then different species with common clock cells suggest decent from a common ancestor.

Cancer Treatment: Scientists have found that the efficacy of drugs is sometimes dependent on the time that the drug is administered. In terms of cancer, a study of the circadian rhythm can maximize the therapeutic effect of chemotherapeutuc drugs (which affect the replication of normal and malignant cells) while lowering the toxic side effects. Edery explains: "By targeting times when normal cells are less likely to be undergoing DNA synthesis, higher levels of drugs can be tolerated, increasing the effectiveness of the treatment" (1).

Moms May Set Our Clocks: A recent study on zebrafish found that mother zebrafish set the circadian clocks of their offspring before birth. Genes associated with the circadian clock are active in the eggs of both fertilized and unfertilized zebrafish. These findings may translate over to humans, in which case our own clocks may be hereditary (6).

Conclusion

The intense research on circadian rhythms answers many questions but poses many more. A functioning biological clock is not common to everyone; for example, many suffer from sleep disorders such as insomnia, which could be caused by a mutation of the clock genes. Researchers must then study mutated genes in addition to normal ones to gain a better understanding of the human genome. The discovery that biological clocks are innate to all living organisms is uniting, but it can also reveal the extreme differences between the systems of different species. It would be interesting to compare the circadian rhythms of organisms that live at the bottom of the ocean and receive no light with human rhythms. Even more interesting would be to compare organisms from different planets. Scientists often describe the biological clock as an adaptation to living on a rotating planet, but what about planets that rotate at different velocities around different suns? Thus, as we grow closer to understanding life, we discover that our new findings only spark endless questions. And the quest for knowledge continues.

 

WWW Sources

1) Physiological Genomics , off homepage

2) Society for Neuroscience , off homepage

3) The Scientist , off homepage

4) Harvard Features Science , off Harvard Gazette homepage

5) Applied Biosystems , off homepage

6) On Health with Web MD , off homepage

 

 

Comments made prior to 2007

I am Tejal acharya,doing microbiology course in M.S.University of Baroda,India.I don't want to send any comment but I have a problem to be solved.The problem is that I have very much busy shedule in day time.I can't get any free time to study as my practical & theory classes run in day time.My classes start at 8:30am to 9:00pm.So,I have to study at night which is not convinient to me.But there is no any other option.My question :Can you tell me how can I set my shedule & biological clock at night?What are the things that I have to take care? It will be a great help in my study,if you could slove my problem.THANK YOU ... Tejal Acharya, 9 December 2006