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 Friday, February 29, 2008
2/29/2008 3:57 PM MST  

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During the billions of years of human (and pre-human) evolution, time has been divided into daily, seasonally, and yearly repeating cycles. Based on these imposed cycles, biological processes have developed that have enabled organisms to exploit temporal niches in their environment and to coordinate physiological responses to optimize metabolic efficiency and survival.

In humans, because of evolutionary pressures, these rhythms have become entrained within our nervous systems. They are generated by the approximately 20,000 neurons located in the master clock in the suprachiasmatic nucleus (SCN) of the brain. It’s proximity to the optic nerves (the nerves connecting the eyes to the brain) is not surprising given the role the day-night (light-dark) cycle plays in this physiology. Its nexus with a part of the brain called the hypothalamus, the region that monitors and controls the body's internal milieu (fluid and electrolyte balance, temperature regulation, and hormonal status, etc.) has important implications as well.

The pacemakers for these rigidly regulated functional ebbs and flows are generated endogenously within the network of SCN nerve cells. More interestingly, each cell in this grouping has intrinsic clock-like abilities incorporated within its genetic makeup. Specific genes (referred to as clock genes) generate the rhythm. This is done using a biological trick called a negative feed back loop. It works as follows. The gene turns on and does what genes do. That is, it creates a protein that is released within the cell. Among other duties, this protein then interacts with the gene that created it and in so doing, turns it off. This process is repeated over and over again. The time it takes for one complete cycle is 24 hours. This nifty process constitutes the molecular basis for the biological clock that forms the basis for the circadian (within a day) cycles that coordinate many bodily processes. Circadian rhythmicity is abolished by damage to the SCN.

These clock genes, and their associated daily cycles, are genetically conserved over numerous species. They play vital roles in many biological phenomena including metabolism, hormonal regulation, fertility/reproduction, thermoregulation, bone formation, fat accumulation and sleep-wake cycles. As such, alterations in circadian periodicity might affect these processes. Mood disorders are even associated with rhythm disruption and clock gene variations. Under conditions of constant light or constant darkness, the synchronicity of the SCN neurons is lost. “Jet lag” seems to be a likely consequence of this environmentally induced perturbation. The advent of the “24 hour society” likely has had adverse impacts on the SCN and probably contributes to the prevalence of sleep disorders estimated to affect 20% of Americans.

In the regulation of hormonal function, timing is everything. This depends intimately on the internal clock mechanism that orchestrates the synthesis, secretion and control of hormones. It is well-known that differing exposure to light modulates hormonal regulation and melatonin levels. Other environmental stimuli such as social signals, poor nutrition, physical activity levels, sleep habits and stress produce effects that are integrated in to the functioning of this intricately balanced system. Common examples of adverse effects are altered menses, infertility, mood swings and difficulty concentrating and learning. Cortisol, the “stress” hormone can single-handedly reset the circadian clock.

It should be obvious that changes in many of the factors discussed above can induce functional alterations in our biological clock mechanism producing adverse health changes in many bodily systems.

 

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