The daily rhythm of life is maintained by a circadian clock in organisms ranging from bacteria to humans. The time kept by a circadian clock enables the organism to respond physiologically and influences its behavior to daily environmental fluctuations. In humans, circadian rhythms help coordinate the timing of our internal bodily functions, including sleep, as well as our interactions with the external world. Virtually all known physiologic parameters and cellular activities are influenced by the body's circadian clock.
Only recently has the medical community, as well as the general public, become aware of the importance of circadian rhythms for human health, safety, performance and productivity. It is now recognized that physical and mental impairments are associated with night-work, which involves over 20% of the work force in industrialized countries. People who work late-night shifts often have problems falling asleep, staying asleep, or waking up. More than 25 million Americans have non-traditional work schedules, and it is estimated that 60 to 70 percent of these people have a chronic sleeping problem. In addition, many industries will employ increasing numbers of workers around the clock (for example, transportation, utilities, public safety, heavy manufacturing and many service industries).
Normal sleep depends on properly functioning circadian rhythm. In humans, obtaining less than the required number of hours of sleep, particularly over several nights, leads to a decreased ability to retain new information, impaired productivity, altered mood, lowered resistance to infection and an increased susceptibility to accidents. Sleep-related traffic accidents annually claim thousands of lives, and operator fatigue has also been shown to play a contributory role in airplane crashes and other catastrophic accidents.
The pharmaceutical industry is now investigating the importance of circadian rhythms for the timing of drug delivery and is interested in developing drugs that could affect the circadian clock of humans, as well as agricultural plants and animals. Numerous health problems, including some forms of depression as well as many sleep, neurological, cardiovascular and endocrine disorders, have recently been associated with circadian rhythm dysfunctions.
In addition, as the elderly continue to become a greater percentage of the population in the United States, as well as in the rest of the world, more and more circadian abnormalities are being observed in older people suffering from various sleep, mental and physical disorders.
Thus, there exists a need to identify molecules associated with circadian rhythm and methods for identifying new therapeutic agents that can be used to modulate circadian rhythm. The present invention satisfies these needs and provides related advantages as well.