Why is it that sleep dysfunction seems to be so ubiquitous in North Americans of all ages? To answer that we must first understand why we sleep, why we need to power down and how our fast-paced modern lifestyle may not be conducive to getting the best sleep.
The Circadian Rhythm
Let’s start by going back to the biology of our natural on/off buttons, the creation of a diurnal (or daily active and inactive) rhythm known as our circadian clock. There is an internal rhythm related to an organism’s adaptation to light-dark or day-night cycles of the planet. “Chronobiology” is the framework that enables such a rhythm to form. It helps to control sleep patterns, feeding habits, body temperature, blood pressure and hormone release, as this molecular clock plays an essential role in every tissue in our body.
Within our brain, in the hypothalamus exists the supra-chiasmatic nuclei (SCN). This is the master pacemaker. Through both neural and hormonal transduction (signaling), the SCN communicates with peripheral organs and tissues to synchronize clock gene expression for an internal circadian rhythmicity. In humans the Circadian rhythm is a self-sustaining mechanism that:
- has approximately 24-hour physiological oscillation
- requires an input mechanism to signal environmental time of day, AKA light signals through skin and eyes
- requires an output mechanism like hormones and neurotransmitters to alter behavior, physiology, and metabolism such as body temperature, endocrine secretion, sleep-wake cycles and locomotor activity.
Let’s take a deeper look into the “key players” of the clock functions:
1. Melatonin is a circadian rhythm synchronizer acting as a neurohormone that reciprocally activates the SCN at two melatonin receptors: melatonin type 1 (MT1) and melatonin type 2 (MT 2) receptors. During evening hours, serum melatonin levels start to rise, reaching peak concentration around 2–4 am, after which melatonin levels decline again until reaching low daytime levels.
For melatonin synthesis tryptophan is taken into the pinealocyte from the blood and converted into 5- hydroxytryptophan 5- HTP is then converted into serotonin by 5-HTP decarboxylase, before serotonin is converted to N-acetylserotonin (NAS) by (AANAT) which converts NAS into melatonin, which is secreted directly into the bloodstream or cerebrospinal fluid.
We know about the importance of melatonin because disruptions in melatonin levels are linked to sleep disorders and chronic sleep deprivation. Melatonin-replacement therapy tries to mimic normal melatonin production and can correct a relative melatonin deficiency and favor sleep initiation and reset the circadian clock to phases allowing persistent sleep.
2. The adrenal gland helps communicate the time of day information from the SCN to peripheral tissues through glucocorticoid secretion. Nocturnal light disrupts this process.
3. Gene expression: activation through output measures such as light exposure will result in altered gene expression which either upregulates or downregulated depending on the tissue.
As mentioned above the input is of course, exposure to light. Light resets the timing of the circadian clock and the rhythms it controls, often measured from the timing of the melatonin rhythm but also including cortisol, core body temperature, and circadian gene expression.
Thus, we can avoid disruption by ensuring consistent and extended exposure episodes of darkness to maintain optimal circadian health, though you may not have to be asleep this entire time. On that note let’s try to understand the relationship between circadian rhythms and the sleep-wake cycle that can be independent, and at other times dependent on each other. Ideally, we want sleep to coincide with the diurnal rhythm and light dark cues as best as possible however we have evolved in many ways to shift sleep wake cycles.
Stages of sleep
A sleep cycle is the progression through the various stages of NREM sleep to REM sleep before restarting it all over again. The stages of sleep are as follows:
Pre sleep alpha waves– nice and calming but not necessarily drowsy
Stage 1: Muscle tone throughout the body relaxes and brain wave activity begins to slow. You can be easily taken out of this stage and occasionally people may experience hypnic jerks or twitches.
Stage 2: approximately 40-60% of total sleep time is spent in this phase characterized by slower theta waves. Here we are actually starting the restorative functions of sleep such as memory consolidation.
Stage 3: the truly restorative stage does not last as long as Stage 2, deep sleep is defined by delta waves. During deep sleep, human growth hormone is released and restores your body and muscles from the stresses of the day. Your immune system also restores itself. Much less is known about deep sleep than REM sleep. It may be during this stage that the brain also refreshes itself for new learning the following day.
REM sleep: REM or rapid eye movement is a funny phase because from a brain wave perspective it would look like you are awake. It first occurs after 90 minutes and is quite short, subsequent REM cycles are longer. Awakenings and arousals can occur more easily in REM as compared with deep sleep preceding it though being awoken during a REM period can leave one feeling groggy or overly sleepy. In this phase your heart rate increases, blood pressure rises, males develop erections and the body loses some of the ability to regulate its temperature. You also should get muscle atonia or muscle paralysis, which occur as a protective means to keep one from acting out their dreams.
Sleep patterns as we age
So how does sleep change throughout our life’s well we know there are stages as anyone with a newborn can attest I am sure. If we observe EEG and sleep/wake states from the fetus, preterm infant, term infant, preschooler, adolescent, to adult follows in an orderly manner depending the central nervous system (CNS) development. Neurological, environmental, and genetic factors, as well as comorbid medical or neurological disorders, will have significant effects on this progression. Newborns have a polyphasic pattern hence the repeated waking’s associated with feedings. Infants and then children eventually assume a biphasic pattern with earlier mornings and a great love of nap times. Adolescents with their changing bodies and hormone requirements require longer stage 3 durations and go back to having somewhat higher sleep requirements. As we reach old age there is a marked attenuation of the amplitude of slow waves- increased likelihood for early risings, waking up throughout the night and reduced sleep quality.
Sleep and Health
It is important to understand the impact of sleep on various systems so we can understand why sleep is so important. Studies are elucidating the link between sleep and many physiologic systems and processes though we will focus on cardiovascular, nervous, immune, skeletal, endocrine and digestive impacts and relationships with sleep.
Cardiovascular: An important epidemiological study from 1979 (Kripke et al.) found that the chances of death from coronary artery disease, cancer, or stroke are greater for adults who sleep less than four hours or more than nine hours a night when compared to those who sleep an average of eight hours.
Nervous system and cognitive function: There seem to be a clear bidirectional relationship between sleep and cognitive function, as sleep is important for memory reinforcement and consolidation, synaptic neuronal network integrity (to facilitate learning), further sleep allows for proper waste clearance in the central nervous system via the glymphatic system. Researchers were able to demonstrate that chronic slow-wave sleep deprivation may result in continuous elevation and accumulation of β tangles (the proposed starting point for Alzheimer’s disease.) We also see that a raised daytime sleepiness had a link with high risks for dementia.
Immune: The role of sleep in immune function is related to protective through upregulation of a number of immune cell lines. One of the things that happens when we sleep is that we can get a better fever response. This is why fevers tend to rise at night, though if we are not sleeping, our fever reaction is not primed diminishing our response and ability to recover. There are also several cytokines, such as interleukin-1, interferon-α, and tumor necrosis factor, actually help promote sleep, once again establishing the connection with sleep and immune function.
Skeletal muscle: Researchers in 2018 found that skeletal muscle function could be impaired by a small change, such as switching a work schedule from day to night for a four-day duration (Bescos). Maintaining a normal circadian rhythm also ensures that we can increase protein content, improving mitochondrial quality, and stimulating regeneration and repairing of cells in skeletal muscle all of which prevent the atrophy or shrinking of muscles.
Endocrine: Wada et al have reported there was an inverse relationship of reported sleep duration and hormone levels among pregnant women and we see similar dysregulation in non-pregnant patients. Sleep demonstrates an increased secretion of anabolic hormones (e.g., growth hormone, prolactin, testosterone, and luteinizing hormone) and decreased levels of catabolic hormones (e.g. cortisol) however, even partial sleep loss alters the HPA axis and leads to transient increases in cortisol level following even partial sleep loss. Elevated cortisol in turn also blocks sleep wake cycles overriding external cues as a form on entrainment. Thus, regulating sleep is a necessary part of management in many hormonal diseases.
Digestive and metabolic: this relationship is important on a number of levels from the production of serotonin (and eventual melatonin), to obesity risks, muscle contractions regulating movement through the digestive system. Sleep encourages a resetting and priming of the digestive system. For example, ghrelin and leptin levels are delayed resulting in our inability to receive and respond to fullness and satiety cues. These differences in leptin and ghrelin may induce increased appetite, possibly explaining the increased BMI observed with short sleep duration in the study populations. Further, chronic sleep deprivation causes impaired glucose tolerance which contributes to memory impairment as a result of decreased hippocampal function.
Finally, sleep plays an incredibly important function in cell cycle regulation. In fact, our G and S phases of cellular replication are circadian, meaning that cell cycle regulation is under circadian gene control. We can see this relationship reflected in results from studies that show shift workers demonstrated melatonin suppression, and cell cycle impairment with correlations to certain cancer types.
As you can imagine there are a number of issues that can arise for disturbed sleep wake cycles. Seven broad categories are outlined in the international classification of sleep disorders.
- Insomnia: difficulty falling asleep; frequent awakenings, including early-morning awakening; insufficient or total lack of sleep; daytime fatigue, tiredness, or sleepiness; lack of concentration, irritability, anxiety, and sometimes depression and forgetfulness; and preoccupation with psychosomatic symptoms, such as aches and pains.
- Chronic circadian rhythm disorder: mismatch between the body’s internal clock and the geophysical environment, either as a result of malfunction of the biological clock or a shift in the environment causing this to be out of phase. There may be cyclic episodes of good sleep, followed by poor nighttime sleep and excessive daytime napping, we see this in shift work syndrome, jet lag- cases where the external cues do not match the response, or cues are being overridden.
- Sleep related movement disorders: often arise from dysfunctions for changing structural functions such as muscle relaxation. These can be related to electrolyte imbalances improper hydration or lactic acid buildup as seen in restless leg syndrome.
- Parasomnias: we have some common and some not so common (i.e. exploding head syndrome) Sleepwalking (somnambulism), sleep talking (somniloquy) and night terrors, nocturnal enuresis which occur during Stage 3 sleep. You may also get REM related parasomnias such as reoccurring isolated paralysis and REM sleep behavior disorder (RBD) characterized by an absence of muscle atonia during REM sleep. RBD is strongly linked with α-synucleiopathies and is considered a prodromal marker for dementia with Lewy Bodies, multiple system atrophy, and Parkinson’s disease.
- Respiratory sleep concerns like obstructive sleep apnea
- Hypersomnias: disorders where individuals sleep too much such as narcolepsy
Connecting all these pieces we can easily become overwhelmed with the complexity and importance of sleep for our functioning. However, the research for management of sleep disorders is equally rich. Many new natural and lifestyle therapies are emerging with significant success.
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