Controlling Our Internal Alarm Clocks: the Mind, the Brain, and the End of Jet Lag

A common fact of modern life is jet lag and the disorienting experience of waking up completely refreshed in the middle of the night. Who at that time has not wished that resetting this internal alarm clock were as easy as resetting an external one? While recent research has shed considerable light on the workings of our internal alarm clocks, little is still known about how to control this alarm clock. In response to this question, this paper will first review important recent research on biological clocks, then consider some possible avenues that might shed light on how one might control the workings of this clock.

The internal alarm clock that wakes up a New Yorker at 3 AM in Beijing is part of a complex biological clock that influences hormones, sleep patterns, metabolic rates and body temperature. In mammals, this clock resides in a small cluster of cells within the hypothalamus called the suprachiasmatic nucleus (SCN) (1). Since the hypothalamus is a part of the brain that also controls hunger and thirst, it is not surprising that biological clocks are also tied to the 24-hour cycle of activity patterns known as circadian (around the day in Latin) rhythms. First coined by Franz Halberg of the University of Minnesota, circadian rhythms help organisms anticipate changes in the environment, such as the rising and setting of the sun (2). Experiments show that nearly every organism has a circadian clock, and even humans that have been isolated in caves or bunkers exhibit circadian rhythms that affect activity and physiology (2). In addition, experiments at the molecular level on fruit flies (Drosophila melanogaster), which share many molecular similarities with humans, demonstrate that peripheral tissues and internal organs also have cellular clocks regulated daily by the central clock in the hypothalamus (2). When the central master clock sends out signals to these peripheral cellular clocks, key clock genes such as CLOCK, CYCLE, PERIOD (PER) and TIMELESS (TIM) respond with periodically changing concentration gradients that trigger tissue specific circadian rhythms. These rhythmic changes include body temperature, blood pressure, heart rate, melatonin concentration, urine production, gastrointestinal acid secretion and liver metabolism (1).

How did researchers link circadian rhythms to these molecular components? Joseph Takahashi, professor of neurobiology and physiology at Northwestern University, discovered the first clock gene in 1971in the fruit fly (3). Fruit flies are advantageous for genetic research since they have short generation times and mutations can be induced in specific genes to rapidly identify particular biological processes (1). As a result, the workings of biological clock mechanisms are best understood in the fruit fly. By 1997, the first clock genes in mammals were found in mice, which accelerated the search for clock genes in higher order animals (3). Recent research has identified at least nine genes that play key roles in the function of mammalian circadian clocks, which operate on a negative feedback loop mechanism with a period of about 24-hours. That is, the negative feedback loop mechanism begins when the two proteins CLOCK and CYCLE bind together and increase the production of the proteins PERIOD and TIMELESS, which then inactivate the CLOCK-CYCLE complex (3). This process is similar to a rise in temperature leading to an increase in cloud cover, which in turn reduces warming by limiting incoming solar radiation. Eventually, researchers hope that the emerging fields of genomics and bioinformatics might shed light on more clock genes that help us understand why people are predisposed to being “early birds” or “night owls” (2).

Furthermore, recent findings by Joseph Takahashi and Aziz Sancar (UNC, Chapel Hill) report that proteins called cryptochromes are located throughout the body and are involved in detecting changes in light and setting the body’s clock (3). These proteins form biochemical pathways that sense blue light and connect sunlight with the molecular components of circadian clocks. However, even plant organisms without the rods and cones found in the eye which transfer light waves into electrical signals for the brain, follow a circadian rhythm. To shed light on this problem, David Burson, a neuroscientist at Brown University, has isolated a cell at the end of a receptor that does not rely on rods and cones to record light signals, but rather connects to the central biological clock via special nerves called retinal ganglion cells that use chemical pigments to convert electrical signals (4).

Clearly, research in the past forty years has expanded much in our understanding of biological clocks and circadian rhythms. However, have we come any closer to understanding how to control our internal alarm clocks? The key may rest in research that addresses the role of volition and the mind in “willing” the brain to perform certain functions. For example, Jan Born at the University of Lubeck, Germany has identified certain hormones that can help us wake up at will. Born has discovered that the anticipation of waking up for the day’s activities releases adrenocorticotrophic hormones (ACTH) that are normally secreted by the pituitary gland during times of stress. Stress hormones are suppressed during sleep, but ACTH concentrations increase in the blood before a person awakes. Born and his colleagues monitored two groups of volunteers: one group was told they would be awakened at 9AM and the other at 6AM. The lights were turned off for both groups at midnight, and researchers began to closely monitor the brain activity and ACTH levels of the subjects. From blood samples drawn every 15 minutes, scientists found ACTH levels to rise sharply around 5AM in the early risers expecting to wake up in an hour, but ACTH levels remained low in the group that expected to sleep for several more hours. Born concluded that the anticipation of a specific wake-up time sets a neurological timer that continues during the sleeping state. In effect, the mental volition to wake up causes a surge in ACTH levels that mark the body’s preparations for an alarm to sound (5).

In a related vein, William Moorcroft, Director of the Sleep and Dreams Laboratory at Luther College, Iowa studied a group of 140 women and 129 men, ranging in age from 21-84. Of these 269 adults, over 50% said that they never use an alarm clock or other external means to awaken, while another 24% reported that they sometimes awaken before the alarm. Moorcroft’s study also employed actigraphy (i.e., an electronic device worn to measure gross motor activity) that tested this ability in 15 people who claimed to regularly self-awaken for three consecutive nights (6). Five people awoke within (and mostly before) 10 minutes of their target time; another five awoke close to their target time on two out of three nights; and out of the remaining five, four individuals awoke close to their target time on one night only. Moorcroft’s study concluded that people do have the ability to set their volition and mental will to regulate neurological patterns of sleep and awakening (7).

The studies conducted by Jan Born and William Moorcroft open new avenues to pursue research on the subject of circadian rhythms and chronobiology. While the molecular research spearheaded by Joseph Takahashi, Aziz Sancar and others has changed our understanding about the physiological process involved in internal alarm clocks, the work of Born and Moorcroft suggest not only that these physiological processes can be controlled by human volition, but also that there is an entity outside the brain and the body that is still intimately linked to it: the mind. Perhaps harnessing the powers of the mind, as distinct from the brain, is the button to reset our internal alarm clocks – and the answer to ridding us of inconveniences like jet lag once and for all.

Web Resources

1. http://www.msi.umn.edu/-halberg; Halberg, University of Minnesota

1. http://www.hhmi.org/biointeractive/clocks/clockwork.pdf; Clockwork Genes, Discoveries in Biological Times; Howard Hughes Medical Institute

1. http://www.nimh.nih.gov/publicat/bioclock.cfm; How Biological Clocks Work; National Institutes of Mental Health

1. http://www.npr.org/templates/story/story.php?storyId=1137854; Blind Mice that See; National Public Radio

1. http://psychologytoday.com/articles/pto-19990501-000014.html; Stirring Sound of Stress; Psychology Today

1. http://en.wikipedia.org/wiki/Actigraphy; Actigraphy; Wikipedia

1. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9130333&dopt=Abstract; Subjective and Objective Confirmation of the Ability to Self-awaken at a Self-Predetermined Time Without Using External Means; PubMed