The circadian rhythm regulates when a person should feel tired, sleepy, hungry, or awake. It is essentially a biological clock centered in the brain and triggered by sunlight.
When the eyes are exposed to light, an electrical signal activates neurons in a cerebral region called the suprachiasmatic nucleus, which governs the neuronal and hormonal signals responsible for a large number of physiological processes — from controlling body temperature to determining rest-activity cycles, feeding behavior or immune cell functions.
These processes ensure that the body's different organ systems are working in perfect synchrony.
But apart from keeping you on a healthy sleep cycle, the circadian rhythm also dictates how your body responds to medication, influencing treatment efficiency.
Depending on the time of day therapy is administered — or where in the circadian cycle the body finds itself — medication effectiveness could be improved, resulting in reduced side effects as well.
Chronotherapy: Timing Treatments To The Circadian Rhythm
Many clinical trials attest to the importance of timing medications to the body's internal clock, which was found successful in a large number of diseases, from cancer and cardiac ailments to allergies and arthritis.
Although this concept, known as chronotherapy, has existed for at least 60 years, it has received little attention from physicians until now. However, since more and more studies confirm the molecular intricacies of cellular rhythms, the extensive influence of the circadian clock is becoming more clearly apparent.
A large number of the body's metabolic pathways reach their climax and then decline according to specific circadian patterns. In consequence, drugs targeting these pathways can work better when taken at particular times of day.
How Circadian-Tailored Therapy Works
In the case of high blood pressure — typically caused by a peptide hormone called angiotensin-2 which triggers the narrowing of blood vessels — treatment is also more effective at night than in the morning. The reason is the receptors for this hormone are more alert at night, increasing the efficacy of hypertension drugs administered at bedtime.
Another example is tumor therapy. Mice studies showed tumors were considerably reduced in animals with breast cancer when therapy was administered in daytime doses. That is because the epidermal growth factor receptor is more active during the day, meaning medication intended to inhibit it works better in the same time interval.
The same theory is applicable to ovarian cancer as well. In dividing tumor cells, DNA replication peaks in the late morning, 12 hours out of sync with normal ovarian cells. This is why chemotherapy is more efficient and produces fewer DNA-damaging side effects when administered in the evening.
The 'Night Owl' Gene And What It Means
Earlier this month, a paper published in the journal Cell uncovered the circadian rhythm can be perturbed in some people due to mutation of the CRY1 gene.
Called the "night owl" gene, CRY1 can slow the internal clock, distort the wake-sleep cycle, and contribute to delayed sleep phase disorder or DSPD.
Authored by researchers from the Laboratory of Genetics at The Rockefeller University, the study explores the importance of the circadian rhythm and how it affects normal sleep patterns.
The laboratory studied the circadian rhythm for more than three decades, during which time researchers identified a number of the genes responsible for keeping the human body on track when it comes to eating and sleeping patterns.
A healthy circadian rhythm operates by having small number of genes activate and deactivate in sync during a 24-hour cycle. The CRY1 gene produces a protein aimed to suppress some of these genes during certain parts of the cycle.
However, researchers discovered the mutation in the night owl gene makes this protein more active than usual, in turn keeping other genes switched off for longer than usual. As a result, the circadian cycle in people with DSPD is 30 minutes longer.
In addition, researchers found the delayed circadian rhythm also leads to slower changes in body temperature and hormone levels, particularly melatonin, which helps regulate sleep. In most people, melatonin levels start to increase from 9 to 10 p.m., but the night owl gene postpones this process until 2 or 3 a.m.