The biology of time: circadian rhythms

SAM FEARNLEY INVESTIGATES CIRCADIAN RHYTHMS IN NATURE

Time itself is just a product of our culture. We devised the concept of time and measurement of it, and it therefore seems questionable, if not implausible, that a biological body clock inherent to our being exists. Despite this, it’s true: sleeping cycles are widely understood to be the reason that only certain durations of sleep are deemed beneficial. Sleep, however, is by no means the only human trait which occurs in cycles. Chronobiology – the study of periodic physiological and behavioural phenomena – has identified a whole host of other biological parameters that vary on a cyclic basis.

Since 4BC, we have known about circadian rhythms in plants, where the movement of leaves follows the sun, ensuring maximum light exposure. It was not until the 13th century that features similar to this were documented in humans, first described in ancient Chinese medical documents. In 1896, a revolutionary but rather unethical experiment revealed how sleep-deprived subjects varied in their tiredness in a cycle of around 24 hours. About 20 years later, J.S. Szymanski was able to prove that animals can maintain their cyclic 24-hour activity levels despite not being exposed to external conditions like temperature and light. This is one of the defining features of any circadian rhythm: a degree of independence from external factors.

20th century genetics is renowned for the emergence of Drosophila (fruit flies) as a laboratory model organism, and, in 1971, Drosophila was used to identify the first gene involved in the manifestation of circadian rhythms. This gene was called the period (‘per’) gene. The protein derived from it has a period of 24 hours and is in its highest concentration at midnight. The gene has a homologous version in humans and a change in this gene is known to cause the disease FASPS (familial advanced sleep-phase syndrome), where sufferers tend to go to sleep around 7pm and wake at around 4am. The complementary gene ‘Timeless’ was discovered in 1994 and is involved in a feedback loop with ‘Period’. In the same year, Joseph Takahashi discovered the mouse ‘CLOCK’ gene: the first to control circadian rhythms in mammals.

In terms of the evolutionary history of the circadian clock, it is probable that a primitive time-keeping mechanism was present in some of the earliest cells. This inherent rhythm would mean that the replication of DNA inside the cell would only take place in the dark, so as not to be affected by any harmful UV radiation from the sun. As organisms became more complex, there was a sudden need for a more sophisticated control mechanism. In humans, this led to a group of neurones in the brain called the ‘Suprachiasmatic nucleus’. This area is at the base of the brain and is the size of a grain of rice, yet controls all circadian rhythms.

For a certain trait to be considered to be circadian in nature, certain criteria have to be met. Firstly, the rhythm must have a regular cycle of 24 hours, and be able to carry on when the environmental factor is excluded. In other words, if the certain trait is determined by luminosity in the environment, then the periodic cycling should continue even in pure darkness.

Secondly, a circadian rhythm is one which can be ‘reset’ using a specific stimulus, called a ‘Zeitgeber’. This is what happens when someone travels to a faraway country and experiences jet lag – the biological clock is re-established. The final requirement is that the rhythm must be independent of any temperature differences. This is more important for animals which take their heat from their environment, like iguanas, whose body temperature varies widely. Temperature compensation counterbalances any reduction or increase in the kinetic activity of molecules.

Circadian rhythms have 24 hour duration but there are other rhythms too. Infradian rhythms last for more than a day, and control migration and the menstrual cycle. Ultradian rhythms are shorter than a day and include the 4-hour nasal cycle. Marine life has tidal (12.4 hours) and lunar (29.5 days) rhythms. Some of the other aspects controlled using these rhythms are: sleep (deepest sleep at two in the morning), alertness (highest alertness at 10am), body temperature (highest at 7pm), physical activity, immune function, digestive activity and hormone levels.

In terms of modern day research, a circadian rhythm gene found in mice (Lhx1) was found in April 2014, apps are being developed to measure sleep cycles (together with integrated light therapy to defeat Seasonal Affective Disorder), and some schools are considering starting school later in the day to better synchronise with circadian rhythms. It seems the daily rhythms of the environment around us have a profound effect on our mood, and control our intrinsic nature more than we ever thought possible.