Sleep and circadian rhythm are highly coupled processes. In the original formulation they were considered independent but interacting. Borbely and colleagues1–4 posited that the circadian process (Process C) had a 24-hour rhythm that interacted with the sleep drive system (Process S) (Fig. 12-1). Process S is envisaged to be like an old-fashioned egg timer. The drive for sleep is at a very low level following the major sleep bout and increases progressively as wakefulness proceeds, i.e., the drive to sleep is related to the duration of prior wakefulness. Humans are programmed to sustain wakefulness for 16 hours but beyond this develop progressive performance impairments. During the day the drive to sleep is counteracted by an alertness signal from the clock. When this alertness signal declines later in the evening, the sleep drive is unopposed, and sleep ensues. During sleep the drive to sleep progressively declines, i.e., the egg timer is flipped, and the sands recover (Fig. 12-1). The situation is actually more complex than this since sleepiness occurs at two times of day, i.e., siesta time in early afternoon and late in the evening. While these processes were initially considered independent, they are not at a molecular level.5,6 Core clock molecules increase their expression in brain when sleep is deprived.7 Moreover, mutations of a clock-associated gene—DEC2, now called BHLEH41—result in short sleep in humans (<6 hours) without evidence of daytime performance impairment.8,9
Two-process model of sleep/wake control. Behavioral state is controlled by the interaction between two processes: process C, the biological clock, and process S, the sleep homeostatic drive. The dark bar from 2300 to 0700 is the lights-off period. For further details, see text. (Reproduced with permission from Kryger MH, Roth T, Dement WC: Principles and Practice of Sleep Medicine, 5th ed. Philadelphia, PA: Elsevier; 2011.)
In this chapter the basis of the clock is described, and the point made that the lung itself has a clock. Sleep is discussed and recent evidence reviewed that sleep alters gene transcription in the lung. The reader will get a background in sleep that will facilitate understanding the cardiopulmonary changes during sleep (Chapter 100) and sleep-disordered breathing (Chapter 98).
MOLECULAR MECHANISMS OF THE CLOCK
The fundamental principles of how the clock ticks are conserved across species, although the specific details, i.e., genes involved, vary between species.10,11
The original concept that the clock involves a distinct molecular mechanism came from identification of mutant fruit flies (Drosophila) with long circadian periods, flies with short circadian periods, and flies with no circadian rhythm.12 Subsequently it was determined that these different flies had different mutations in the same gene, which was given the name period (per), ...