The Pharmaceutical Journal Vol 275 No 7376 p644 19 November 2005fficeffice" /> Interactions emerge between biological clocks Biological clocks, or circadian rhythms, control behaviour and essential life processes, including eating, sleeping, seasonal migrations and cell proliferation. Some sort of time keeping is part of the fabric of life, and regulatory clocks vary over a wide range of dimensions, from the millisecond operations of neuronal activity to the seasonal changes shifting the amount of daylight during the year and prompting variations in our habits.
Timekeeping mechanisms have hitherto been considered in isolation, but unexpected interactions between clocks have emerged. These have been examined by Martha Gillette of ffice:smarttags" />Illinois and Terence Sejnowski of California in an article in Science for 19 August.
Interesting questions about why life processes are subject to biological clocks involve genetic, cellular and molecular considerations. One that has been broadly studied is that of mitosis, regulating the dynamic process of eukaryotic cell division. Cells of different types and sizes are governed by different amounts of time in different parts of their cycle. Key proteins, the cyclins, undergo phosphorylation, proteolysis and spatial targeting as they progress.
Yeast cells show reductive and oxidative phases of metabolism, their replication being restricted to the reductive phase. It is not known whether their cell division and metabolic cycles are linked. Associated metabolic and mitotic oscillations have been observed in human cell cultures, so there may be similarities between the respective clocks. Moreover, yeast shows a high frequency oscillation synchronised with respiration phases.
Cycles of cell division and metabolism also appear to be co-ordinated with the familiar circadian pacemaker, an innate timekeeping mechanism governing the activity over roughly 24-hour intervals in an organism’s lifetime. In mammals the circadian clock is controlled by the suprachiasmic nucleus of the brain. Treatment of cultured mammalian cells with haem synchronises gene expression in the circadian clock — further evidence that this and the metabolic states are coupled in some way.
The most familiar timing system in organisms is the daily cycle of sleep and wakefulness. Studies of human sleep patterns and performance indicate that the sleep-wake cycle is regulated by dual brain mechanisms, the drive to sleep, increased with time spent awake and restorative during rest, and the circadian process in the suprachiasmic nucleus of the brain, which organises sleep and wakefulness in relation to night and day. Other brain regions may track time spent awake and also effects of food restriction. It is loss and restoration of brain energy stores that govern sleep homoeostasis, something attributable to gene regulation. Intensity of light plays a part in the cycle in many organisms.
There is a need to concentrate on the interrelationships between the many cyclical processes found in organisms and their interaction across a wide range of temporal and spatial scales, since natural clocks do not function in isolation. |