Trait#62: Sleep/Wake Cycle
Monday, April 13, 2020. Author FitnessGenes
Monday, April 13, 2020. Author FitnessGenes
In your previous CLOCK and metabolism trait, we discussed circadian rhythms – biological processes which follow an intrinsic cycle of 24 hours. Your sleep / wake cycle is an example of a circadian rhythm, with wakefulness followed by sleep and then wakefulness in a rhythm that is approximately 24 hours.
The timings of your sleep / wake cycle – that is, when you’re likely to wake up and go to sleep – is controlled by a system known as the circadian clock system. This system syncs your sleep / wake cycle with patterns of light and dark in the environment so that you tend to be awake during day and asleep at night-time.
Our sleep / wake cycle is tied to the production of hormones that make us wake up or feel sleepy at appropriate times. In the morning we produce more of a hormone called cortisol, which promotes wakefulness. By contrast, during the evening we start to produce more of a hormone called melatonin, which makes feel sleepy.
It’s also worth noting that we have a so-called ‘homeostatic drive’ to sleep. This is a need to get a constant amount of sleep over time. This homeostatic drive explains why we may ‘sleep in’ on some days after missing out on sleep earlier in the week.
Your Sleep phase trait will focus on the intrinsic timings of your sleep / wake cycle as regulated by the circadian clock system. This is sometimes referred to as your 'chronotype' and it determines your natural sleep patterns and whether you prefer mornings or evenings.
The key component of your circadian clock system is a structure called the suprachiasmatic nucleus (SCN), which is located in the hypothalamus of your brain. This structure has an endogenous central pacemaker that sets our circadian rhythms.
The SCN also receives inputs from the retinas, so that our circadian rhythms, including our sleep/wake cycle, are synced with changing amounts of light in the environment. In this respect, we say that light is a zeitgeber – it’s an environmental cue that 'entrains' our circadian rhythm to match the 24 hour light/dark cycle caused by the Earth’s rotation.
Due to this principle of entrainment, our sleep/wake cycle is ordinarily around 24 hours. To adopt more precise terminology, we say that the period of our sleep/wake cycle is 24 hours. Period refers to the length of time to complete one cycle – i.e. the time taken to go from waking, to sleeping and back to waking again.
While the average period for our sleep/wake cycle is about 24.2 hours, there is considerable variation between individuals. Some of us may have naturally shorter or longer sleep/wake cycles. People with shorter period sleep / wake cycles may tend to wake up and go to sleep earlier. By contrast, a longer period causes people to naturally go to sleep later.
Similarly, some of us may have sleep cycles that are shifted either earlier or later (phase-shifts), so that, respectively, we naturally wake and fall asleep at earlier or later times. Sleep / wake cycles that are shifted earlier are known as having an advanced phase. Those that are shifted later are termed as having a delayed phase.
This variation in the intrinsic timings of our sleep/wake cycles (due to different periods and/or phase-shifts) determines whether we’re more likely to be an ‘early bird’ or a ‘night owl.’ In other words, it determines our chronotype.
So, what causes this variation in sleep/wake cycle timing between individuals? The answer lies in small differences in the functioning of our circadian clock systems. These variations are, in turn, significantly influenced by our genetics. In this respect, we consider variants of genes that encode proteins that make up our endogenous central pacemaker. The particular gene variants we inherit play a key role in determining when we’re likely to naturally wake up and fall asleep.
Our circadian clock system has an endogenous central pacemaker. This is a nifty molecular mechanism that causes levels of proteins (called Clock proteins) to oscillate up and down in a rhythmical fashion.
The exact workings of this molecular oscillator mechanism are quite complicated and involve cycles of switching so-called Clock genes ‘on’ and ‘off’. Variation of these Clock genes can affect the timings of circadian rhythms and thereby alter the timing and period of our sleep/wake cycle.
During the morning, two key Clock proteins called CLOCK and BMAL1 are activated and join together (to form the CLOCK:BMAL1 complex). Both CLOCK and BMAL1 are examples of what we term “transcriptional activators” – molecules that switch ‘on’ genes and stimulate the production of proteins encoded by those genes.
CLOCK and BMAL1 switch on two Clock genes in particular: Per and Cry. They switch on these genes by binding to a stretch of our DNA called an E-box (enhancer box). Activating the Per and Cry genes stimulates the production of the corresponding PER (Period circadian protein) and CRY (cryptochrome) proteins. As a result of this, levels of PER and CRY gradually rise throughout the day.
The PER and CRY proteins, however, also act to inhibit their own production. During the evening, the PER and CRY proteins join together and act to inhibit CLOCK and BMAL1. This leads to less activation of the Per and Cry genes. Consequently, levels of PER and CRY proteins drop throughout the night-time.
As levels of PER and CRY drop, however, there is less inhibition of the CLOCK and BMAL1 proteins. By the next morning, CLOCK and BMAL1 are free to re-activate the Per and Cry genes, restarting the cycle.
There are different types of PER and CRY proteins, including:
These are encoded by genes which are appropriately named Per1, Per2 and Per3; and Cry1, Cry2. Variants of these genes may affect the function of their corresponding proteins and therefore influence the timings of your sleep/wake cycle.
For example, a SNP (rs228697) causes a C-->G change in the DNA sequence of the Per3 gene. This single letter change alters the function of the PER3 protein, which may lengthen the period of the sleep/wake cycle. As a result of this, people with two copies of the G variant (or allele) of the PER3 gene are more likely to go to sleep and wake up later.
Your Sleep phase trait also analyzes variants of your CLOCK gene, which encodes the CLOCK protein. Again, different variants of this gene affect the timings and period of your sleep/wake cycle.
Our TrueTrait algorithm analyzes several different gene variants (explained in the previous section) to figure out your chronotype – i.e. whether you’re naturally more likely to be a morning versus evening person.
Based on your gene variants, it’s possible to predict whether the period of your sleep/wake cycle is likely to be longer or shorter than average. Some gene variants are also associated with sleep/wake cycles that are either shifted earlier (advanced phase) or later (delayed phase).
Despite variation in the timings of our sleep / wake cycle, it’s important to remember that we entrain circadian rhythms (including our sleep/wake cycle) to sync up with natural patterns of light and darkness. For example, if we spend time in a different time zone, we eventually (after experiencing initial jetlag) adapt to the new waking and bedtime conventions. Therefore, despite individual differences in the period of our sleep/wake cycles, most of us are able to stick to conventional waking times and bedtimes
Nevertheless, gene variants that cause significant phase-shifts in our sleep/wake cycles (and thereby cause people to sleep very early or late), may cause difficulty with conventional waking times, bedtimes, working hours etc.
Your Sleep phase trait classifies your sleep / wake cycle (chronotype) under one of six categories:
If you’re in this category, the period of your sleep/wake cycle is likely to be close to 24.2 hours. You are unlikely to have any difficulty with conforming to conventional waking and sleeping times. You may also not notice any preference for either mornings or evenings.
Mild evening preference
Individuals in this category may have a sleep/wake cycle with a slightly longer period. Consequently, such individuals are likely to fall asleep later in the evening. People with a mild evening preference may also feel less alert in the mornings. Nevertheless, people with a mild evening preference likely still cope well with conventional waking and bedtimes.
Increased evening preference
People with a longer sleep / wake cycle tend to fall asleep later in the evening, as their levels of melatonin (the hormone that promotes sleepiness) peak later. If you are in this category, you are highly likely to be more alert in the evenings and may struggle to be alert in the mornings.
Delayed sleep phases
A delayed sleep phase means that your sleep/wake cycle is shifted later (by between 2 and 6 hours). As the graph below shows, people with a delayed sleep phase tend to fall asleep (light blue box) much later than those with average sleep / wake cycles.
If you have a delayed sleep phase, you likely struggle to fall asleep before 1 am and have difficulty waking up in the morning. You also probably struggle with conventional waking and bedtimes and have significant difficulty being alert in the mornings.
Mild morning preference
Individuals in this category may have a sleep/wake cycle with a slightly shorter period. Consequently, such individuals are likely to wake up earlier in the morning and fall asleep earlier in the evening. People with a mild morning preference may also feel less alert in the evenings. Nevertheless, people with a mild morning preference likely still cope well with conventional waking and bedtimes.
Increased morning preference
People with a shorter sleep / wake cycle tend to wake up earlier and fall asleep earlier in the evening, as their levels of melatonin (the hormone that promotes sleepiness) rise earlier. If you are in this category, you are highly likely to be more alert in the mornings and may struggle to be alert in the evenings.
Advanced sleep phases
An advanced sleep phase can be considered as the opposite of a delayed sleep phase – it describes a sleep / wake cycle that is shifted earlier. As a result, individuals with an advanced sleep phase tend to wake up extremely early (e.g. before 5am) and also fall asleep earlier (e.g. 7.30 pm). This may cause difficulties adhering to conventional waking times and bedtimes, with such individuals feeling tired and being less alert in the early evenings.
For advice on how to optimize your sleep based on your particular sleep / wake cycle, be sure to check out your actions.
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