Sleep as a Foundation for Health and Longevity
In this paper we set out to address the following aspects of sleep:
- Why we need sleep
- Melatonin, adenosine sleep pressure and circadian rhythm
- REM and NREM phases: Dreams, memory, sleep spindles and growth
- The health consequences of sleep deprivation
- Tactics to get a better night’s sleep
INTRODUCTION
According to recent research recommendations, the optimal amount of sleep per night for adults is between 7-9 hrs maximum [Watson NF et al., 2015; Daza EJ et al., 2019; Chaput J,P et al., 2018]. However, evidence indicates that fewer than a third of us are actually achieving this required level of slumber, in what has been variously described as a ‘global epidemic,’ of sleeplessness [Chattu, VK et al… 2018; Centre for Disease Control – Sleep].
It comes as little surprise when we observe modern living trends. A rising tide of mobile use, work pressures, urban noise, light pollution, not to mention a whole plethora of other digital distractions all clearly favour wakefulness. Indeed, we are recognising this at an individual level, with a recent large scale global survey showing only half of the adults surveyed were satisfied with their sleep levels [Phillips – Global Sleep Survey – 2020].
As we will explore here, the consequences of a lack of sleep to global health stretch far beyond tiredness and reduced concentration. In point of fact, they are potentially catastrophic. They serve as a major disruptor to our everyday physical and mental wellbeing, with strong evidence to show that long term deleterious sleep habits contribute to disease development and premature mortality. In this article, we review why we need sleep, what regulates it, research findings that document the consequences of poor sleep hygiene, and tactics to ensure we get the required levels for our health.
WHY DO WE NEED SLEEP?
Sleep serves critical physiological functions in the body. It is fundamental to health, and indeed, life. The latter is corroborated by conditions such as the rare neurodegenerative condition ‘Fatal Familial Insomnia.’ This inherited disease typically starts during middle age and renders individuals unable to sleep, which can prove, as the name suggests, terminal in as little as 7 months [Llorens, F et al., 2017].
Ironically, although we spend on average a third of our lifespans asleep, [Aminoff MJ, et al 2011] the precise processes occurring in the body are still being discerned by the research community. What we do know is that sleep has key restorative, regulatory and maintenance roles, that are so essential to our wellbeing that they offset the evolutionary disadvantage of being in a state of vulnerability every night. This includes homeostatic maintenance, appetite regulation, metabolic control, learning, memory processing, cognition and immunity, amongst others. Indeed, in the brain there are numerous critical functions that are restored by nightly sleep as we discuss in the next section.
REM, NREM TYPES OF SLEEP AND THE BRAIN
When we are asleep, there are two distinct phases, or states, we experience and cycle through every 90 – 120 mins that are characterised by different brain activity. These are respectively known as rapid eye movement (REM) sleep and non-rapid eye movement (NREM) sleep. NREM sleep occurs more predominantly during the first part of our night’s rest. It consists of three stages that successively increase in depth, with the last, stage 3, considered the most recuperative [Moser et al., 2009]. Here, brain activity is characterised by slow oscillations that are detectable by electroencephalogram (EEG), and is therefore referred to as slow-wave sleep [Saper, CB et al., 2010]. NREM slow wave sleep is thought to serve a key restorative function to the brain, whereby critical activities like molecular, cellular, and network level maintenance and repair can take place.
Aside from this, phenomena called sleep spindles are observed in the earlier stages of NREM. Here, spikes of activity go from the cortex of the brain (central to all conscious activity, voluntary movement, long term memories and thought – amongst other roles), to the thalamus (an effective central relay station for the brain). There is evidence that sleep spindles maintain learning capacity, move short term memories from a region called the hippocampus to long term storage in the cortex, and enable you to learn motor skills – like typing on a keyboard for example [Laventure S,et al., 2016]. Interestingly, the amount of sleep spindles observed declines in older age.
In contrast, during REM sleep your brain shows similar activity to wakefulness (increased activity in some areas in fact) and this is when we typically dream. Our skeletal muscles become paralysed, we also experience intermittent muscle twitches, fluctuations in body temperature, and increased respiratory activation. The function of REM sleep is still not fully understood, but key data indicate it facilitates learning and memory consolidation by altering neuronal connections (synapses) [Boyce R et al., 2017].
In addition, there is increasing evidence that shows that there is a clearance of waste products and metabolites generated by the brain during the day’s activities, whilst we are asleep. This is thought to be enabled by a ten-fold increase in the circulation of the fluids surrounding the brain and brain membranes [Xie et al., 2013].
HOW IS OUR SLEEP REGULATED?
There are three main mechanisms that regulate our sleep-wake cycle: the circadian rhythm; hormone regulators like melatonin; and molecules called somnogens – like adenosine.
CIRCADIAN RHYTHM
An individual’s circadian rhythm is a timed rotation between what the body perceives as day versus night. This 24 hr* cycling is endogenous to the body and originates from, and is regulated by, part of the brain known as the suprachiasmatic nucleus (SCN) [Abbott et al., 2015]. It influences all other regions of the brain and all other organs. As well as determining wakefulness, it regulates multiple other bodily functions including metabolism, appetite, core body temperature, hormone release, and emotional state. It can be influenced by several factors with light and darkness being a fundamental cue.
(*Our endogenous clocks have been shown in experiments to actually just run over 24 hr ;Czeisler CA, et al., 1999)
MELATONIN
The hormone melatonin is also a significant regulator of the circadian rhythm. It rises significantly as the sun sets and reaches a peak in the early hours of the morning (2-4 AM). Conversely, input from light sensors in the retina to the SCN (described above as regulating the circadian rhythm) directly inhibit melatonin secretion and promote wakefulness. Nearly all our organs have receptors for melatonin, so its influence is pervasive.
In the early hours of the morning, a hormone steroid called cortisol starts to rise rapidly, and induces waking. Other factors like temperature – we’ve evolved to fall asleep in cool conditions – medicinal drugs, exercise and meals can also alter this endogenous clock.
ADENOSINE
Another system that governs our need for sleep is the increase and presence of several sleep-inducing molecules called somnogens. These continue to build up the longer we are awake. One of the most important of these is called adenosine. This chemical accumulates in the brain during wake time, influencing neuronal pathways to increase sleepiness. It only resets once we get enough sleep [Blanco-Centurion C, et al., 2006]
THE HEALTH CONSEQUENCES OF SLEEP DEPRIVATION
In the short term, sleep deprivation can increase stress, the risk of poor mental health, accidents, injury, and lead to cognitive, memory and performance deficits. Longer term, sleeping fewer than 6 hrs a night has been identified as a contributory factor to developing diseases that are some of the leading global causes of death. Examples include cardiovascular diseases, stroke, cancer and diabetes. In fact, some studies have indicated sleeping 6 hrs or less a night can increase the risk of premature mortality ten-fold, compared to recommended levels [Hafner, M et al., 2016]. Many studies indicate a U-shape relationship with sleep and mortality, whereby persistent low levels (less than 6 hrs) or high levels (+9 hrs) of sleep are associated with a higher mortality rate [Cappucio et al., 2010]. We discuss the evidence for some specific deleterious effects of sleep deprivation and disease contribution below.
CARDIOVASCULAR DISEASES (CVD)
Cardiovascular diseases are the leading cause of death globally, according to WHO statistics accounting for 31% of all recorded deaths. The primary lifestyle factors linked to cardiovascular disease development include tobacco use, unhealthy diet, obesity, physical inactivity and harmful use of alcohol. There have been an increasing number of studies over the past two decades, however, that indicate that sleep duration can also contribute to the risk of disease [Wolk et al., 2005; Nagai M, et al., 2010; Yin J, et al., 2017].
For example, one meta-analysis study examined the association between sleep duration, risk of all‐cause mortality and cardiovascular disease [Yin J, et al., 2017]. The study concluded that that the lowest risk for both was observed with a sleep duration of 7 hours per day. Furthermore, the risk for all cardiovascular disease increased by 6% for every one hour slept less than this, and 12% for every one hour slept in addition. When this was broken down into different types of CVD, notably sleep duration of equal to 6 – 7 hrs showed the lowest risk for stroke, and the starkest increase in risk was seen when sleep duration of ≥9 hr was observed.
CANCER
The risk of cancer development and sleep remains controversial, with disparate conclusions reached by researchers over the last twenty years. However, a number of studies have determined sleep as one of the modifiable risk factors for some specific types of cancer.
For instance, a European wide study in 2012 that included 23K+ middle-aged individuals concluded that participants sleeping less than 6 hr were at increased risk of all chronic diseases, compared to those gaining 7-8 hr day [von Ruesten A, et al 2012]. This included all forms of cancer. In contrast, a large-scale meta-analysis in 2018, that aggregated data from 65 studies in several countries globally, found there to be no general association between sleep duration and cancer risk [Chen Y. et al., 2018].
The authors of the 2018 study did note there were two exceptions to this outcome [Chen Y. et al., 2018]. The first was in the specific Asian populations included in the analysis (China, Japan and Singapore in this case — other Asian countries were not covered). Here, an increased chance of getting all forms of cancer were observed when routinely sleeping ≤5 hrs or ≤6 hrs versus a reference of 7 hrs (+36% or an odds ratio of 1.36: 1). Secondly, the incidence of colorectal cancer appeared to increase in individuals who were sleeping ≥ 9 hrs.
A recent Spanish study examined the sleep patterns of 2.5K people diagnosed with colorectal and, additionally, gastric (stomach) cancer versus a control group of 3.6K subjects. They concluded, that compared to 7 hrs, short (≤ 5 hr) or long sleep (≥ 9 hr) duration was associated with both types of cancer [Papantoniou K. et al., 2021]. Furthermore, they noted that long, frequent naps (≥ 30 mins, 6-7 times a week) were also linked with colorectal cancer.
Another Europe-based study, in fact, one of the largest scale studies of its type – in a UK cohort of over a million women, found no association between sleep duration and breast cancer [Wong A.T.Y, et al., 2019]
DIABETES
A meta-analysis of 17 studies including 737K adults, indicated that those with short sleep duration (≤ 6 h) and long sleep duration ( ≥9 h) increased their risk of developing type 2 diabetes by 8 % and 14% respectively, compared to what they referenced as normal sleep duration of 7 h [Lu, H et al., 2021]. Another review of lifestyle factors and the risk they pose for developing Type 2 diabetes had similar conclusions, but indicated there may be gender differences — with women increasing their risk with longer sleep durations, and men withdeficient slumber [Ismail L. et al., 2021]. The authors went on to highlight the contribution of a condition called obstructive sleep apnea, where the throat muscles relax when you’re asleep reducing oxygen levels (hypoxia). They stated this could potentially lead to inflammation, as a precursor to Type 2 diabetes [Ismail L. et al., 2021]. Conversely, it should be noted that having Type 2 diabetes has itself been linked to a number of sleep disorders, which may be related to the disease itself or concurrent health complications [Khandelwal D. et al 2017].
OBESITY
A wealth of literature has linked short sleep duration to obesity over the past few decades. One of the most cited was a study by Cappucio et al., in 2008, that analysed data from over 630K individuals, 30K+ of whom were children. It concluded that there was clear association between short sleep duration (defined as < 5 hr for adults and < 10 hr for children) and a BMI>30 for adults or BMI in the 95th percentile for children.
NEURODEGENERATION, DEMENTIA AND ALZHEIMER’S DISEASE
As we discussed above, key restorative pathways and metabolite clearance from the brain are thought to occur whilst we sleep. As such, it is sensical that several research studies have focused on sleep as a variable lifestyle factor for diseases that impact the brain. Furthermore, several mechanistic theories around the accumulation of toxins and metabolites (like Beta-amyloid for example), have been proposed [Vanderheyden WM, et al., 2018].
In a recent peer-review study, authors looked at middle-age sleep patterns and the overall incidence of dementia by following 7959 subjects over a period of 25 years. They concluded that continual short sleep duration of < 6 hr during your 50’s, 60’s and 70’s is associated with a 30% increased risk of dementia, versus obtaining 7 hr per night [Sabia, S et al., 2021]. This was seen as independent of other factors including sociodemographic, mental health, cardio-metabolic or other health variables. The researchers found no evidence for any link between long sleep duration and dementia risk.
Sleep disorders and insomnia, especially in mid-life (~50) have been linked to the higher incidence of dementia in older age in other research studies too [Sindi S, et al., 2018; Shi L, et al., 2018], as well as the development of Alzheimer’s disease [Shi L et al., 2018; Vanderheyden WM, et al., 2018].
DEPRESSION AND MOOD
Inadequate sleep has been linked to low mood by multiple research publications. Sleep disorders and poor sleep quality has been shown to have a bidirectional relationship with the development of depression [ Riemann D, et al 2001]. There have been several studies showing the vulnerability of shift workers – who typically will experience inadequate or altered sleep patterns – to mood disorders, including anxiety and depression. One randomised clinical study that simulated shift-work conditions, concluded that having what they referred to as a ‘circadian misalignment’ to one’s natural sleep rhythm resulted in negative mood effects [Chellappa SL, 2020]. Furthermore, recent research has linked sleep deprivation specifically with an inability to suppress unwanted memories and negative thoughts – the latter ruminations can be key drivers for depression and other psychiatric conditions [Harrington MO, et al 2021].
OVERALL MORTALITY
As we’ve covered here, there is a large body of evidence indicating that short and long sleep duration can adversely affect health. It follows on that a number of research groups have sought to investigate the impact of our habitual sleep patterns on our mortality, and also our longevity.
In a systematic review and analysis of large-scale population studies (1.3 million participants), Cappucio and colleagues concluded that short sleep duration (typically < 7 hr or < 5 hr in some cases) conferred a 12% extra risk of death versus those sleeping 7 – 8 hrs. On the other end of the spectrum, those routinely sleeping longer than 8 or 9 hrs were at a 30% higher risk of death. They referred to this as a U-shaped trend. Note that this was a pooled analysis of several published papers, so many of them differed slightly on their individual definition of ‘short’ or ‘long’ sleep duration.
In a study on longevity, research indicated that long-lived individuals (85 – 105) maintained regular sleep patterns, and whilst they slept less than individuals between 60 – 70 yrs of age, they had the same amount of NREM slow wave sleep, especially stage 3. In addition, they had a healthy HDL to LDL lipid profile [Mazzotti et al., 2014]
HOW THEN TO GET A BETTER NIGHT’S SLEEP?
LIGHT
We have light sensitive receptors in our retina that directly feed into our circadian rhythm and melatonin levels. Artificial lighting causes us to detach from using the suns natural rising and setting as a cue for our sleep, and hence to stay awake longer. Light is measured in a unit called lux, and full sunlight is typically 25,000 lux. Several studies show that exposure to daylight helps improve the quality and duration of sleep [Boubekri M, et al., 2014]. However, individuals who have later exposure to artificial light experience more nocturnal awakenings and less slow-wave sleep. The light intensity, even from a weak indoor bedside light (10-15 lux), has been shown to suppress melatonin release and delay the evening sleep phase of our circadian rhythm [Boivin DB, et al., 1994; Blume C et al., 2019].
Blue spectra light is a type of illumination that’s typically omitted from digital devices, our tv screens, mobiles, and laptops etc. This is a particularly potent disruptor of sleep, as our retinal receptors are more sensitive to it than other light spectra. This creates a strong incentive to disengage from our phones and electronic devices several hours before we are thinking of going to sleep. Some manufacturers mention they have night modes to combat this (reducing the emission by 67% in some cases). However, it still amounts to high light intensity, typically close to your face. The best thing is to avoid use altogether, or use the minimal brightness on your phone, which may be more effective than any night shift mode [Blume C et al., 2019].
TEMPERATURE
Our ancestors typically slept exposed to the elements and we have evolved to sleep in cool conditions relative to the daytime when we are active. In fact, our core body temperature drops as a precursor to sleep as a result of our blood vessels dilating in our extremities (hands and feet) [Harding EC, et al., 2019]. Our body’s circadian and hormonal regulators respond to this decrease to help elicit sleep. A warm bath or shower at least an hour before sleep (if its immediately before bed it can warm you up), can also help induce a cooling effect [Harding EC, et al., 2019].
In many modern heated homes, we often have thermostats or a continually maintained temperature. A drop in temperature at night may not occur and we are working against this natural sleep-inducing mechanism. Lowering the temperature on your thermostat at night can help here. Optimal room temperatures are typically between 19 – 21 C [Harding EC, et al., 2019]. A large-scale population analysis in the US concluded there was a robust link between atypically high night-time temperatures (as a result of climate change) and insufficient sleep [Obradovich N et al., 2017]. This was most marked in the elderly and low-income individuals.
ALCOHOL
Alcohol has sedative properties. Drinking before sleep can help induce deep sleep initially. However, once asleep, alcohol, especially in medium to high doses, is a potent disruptor of our natural sleep cycles. This typically manifests in the last half of the night when in REM. Circulating alcohol cuts short the time we spend asleep and can induce early awakening [Ebrahim IO et al., 2013]. Furthermore, movement during REM sleep is amplified, as is the potential for sleep apnea. Here, our throat muscles relax and we snore with adversely affected breathing, all of which combined result in poor sleep quality.
CAFFEINE
Caffeine beverages are the most widely consumed in the world, often in the form of coffee. Caffeine stops the effects of sleep-inducing adenosine, by blocking its receptor, and is quickly absorbed and effects our system within 30 mins. It is cleared much more slowly, however, with a half-life ranging from 2 – 10 hrs depending on several factors, including how much is consumed and individual differences in caffeine metabolism [ O’ Callaghan et al., 2018]
Researchers have found that there is a cyclical relationship between caffeine use and inadequate sleep whereby feeling tired in the morning leads to high caffeine intake, which consequently leads to poor sleep quality. In one study, even a relatively low dose of 200 mg, two brewed cups of coffee, at 7am were shown to affect sleep quality 16 hr later compared to a placebo [Landolt HP, et al, 1995].
ALLOW AMPLE SLEEP OPPORTUNITY
If you are aiming for optimal levels of sleep, (7-8 hr) its stands to reason that you may need to allow yourself longer than this in bed. Having a wind-down period set aside for reading a book, or relaxing before you drift off is good practice. Your bed should be a place of relaxation and comfort, whilst ensuring your body is sufficiently supported at your natural pressure points when lying down.
NOISE
Noise pollution, especially in urban environments with traffic, can interrupt sleep. In fact, the WHO has specified that night noise should not exceed 40 decibels, and that 55 decibels and above may put individuals at serious health risks, including elevated blood pressure and heart attacks. It has worked together with the EU for example to introduce laws that ban noise at night.
Partners snoring can have a similar effect for some people. If the noise cannot be blocked out, investing in ear plugs may advisable!
SLEEPING PILLS…
Although there are several pharmacological drugs approved for use as a short-term fix to induce sleep, evidence suggests they are not an effective long or even short term replacement for naturally induced sleep. There are several contraindications, in that the quality of the sleep may be impaired, there are possible addictive characteristics (benzodiazepines for example) or there is a balance to be struck between obtaining adequate sleep and having following day sleepiness and decline in cognitive function [Lie JD et al., 2015]
CONCLUSIONS
According to decades of research, it is clear that sleep needs to be prioritised as a lifestyle variant due to its critical function for our health, healthy ageing and, ultimately, poor sleep hygiene has dire implications for our mortality. Routinely obtaining 7 – 8 hr slumber a night specifically has shown to be optimal and have protective effects against disease development. Peer-review research has clearly identified the contribution of consistently obtaining shorter or longer periods of sleep (≤6 hr or ≥ 9 hr —for adults) to cardiovascular disease, obesity, dementia, type 2 diabetes, gastric and colorectal cancer and mood disorder development.
Good sleep practices include getting daylight exposure during the day, avoiding strong artificial light in the evening, including that from digital devices, ensuring optimal room temperatures, minimising noise, avoiding alcohol before bed and reducing or eliminating caffeine consumption.
© SX2 VENTURES 2021
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