Sleep and Aging II: How does the sleep of the elderly and sick differ from the sleep of the young and healthy?

In the last part, we talked about what circadian rhythms are, what genes provide them, and how mutations in these circadian genes can affect health. Well, sleep disturbances cannot but affect the course of circadian rhythms. Of course, sleep disorders do not occur on their own. These are almost always manifestations of some other painful processes in the body. Such processes may include problems with internal organs and cognitive impairment. At the same time, a number of diseases often observed with sleep problems are also detected in older people. Coincidence? Not at all necessary.

Aging and longevity

A series of articles conceived as part of the “biomolecules” special project for the Science for Life Extension Foundation.

In this series, we will consider the general problems of aging of cells and organisms, scientific approaches to longevity and prolongation of healthy life, the connection between sleep and aging, nutrition and life expectancy (let’s turn to nutrigenomics), we will talk about organisms with negligible aging, we will cover the topics of (epi)genetics of aging and suspended animation

Of course, the phenomenon of aging is so complex that it is too early to talk about radical successes in the fight against it or even a clear understanding of its causes and mechanisms. But we will try to select the most interesting and serious information about the discovered connections, model objects, developed and already available technologies for the correction of age-related disorders.

A brief summary of the special project is highlighted in the video “To grow old or not to grow old? // Everything is like animals.” You will learn more from our articles.

Stay tuned!

Circadian rhythms, and with them sleep, can be disrupted in anyone. It’s enough to stay late at the computer or fly a couple of thousand kilometers from east to west (or vice versa). A little earlier we talked about how mutations in the “internal clock genes” (and therefore sleep disturbances) lead to metabolic problems and, ultimately, can cause a variety of diseases. Interestingly, older people experience both sleep disorders and metabolic disorders at the same time. Most likely, this is somehow connected.

Increasing Orthodox phase

If you feel that the slow phase does not have as much time as is needed for normal rest, you can increase it. Most often, such problems appear in people who cannot fall asleep for a long time, because the first sleep cycle contains the longest orthodox phase, and then it becomes less and less long. To get rid of this problem, you should follow these simple recommendations:

• Establish a rational sleep-wake schedule.
• Go to sleep and wake up at the same time, even on weekends.
• Play sports during the day, but physical activity should not be given to the body 3 hours before resting at night.
• Organize a favorable climate in the relaxation room and a comfortable sleeping place.
• Do not drink alcohol, caffeinated drinks, energy drinks, or smoke before going to bed.
• Watch your diet - you cannot overeat at night, eat chocolate or any other sweets, as these foods have a stimulating effect on the nervous system.

Truths and myths about sleep for older people

Older people often experience daytime sleepiness and are therefore considered to have trouble sleeping at night. However, a study of two groups (the first of 30 men and women with an average age of 25 years, the second of 23 with an average age of 83 years) showed that older people only think that they experience drowsiness more often and more strongly than younger people [1].

Participants took a test to determine the frequency of periods of latent sleepiness during the day (Multiple Sleep Latency Test). This technique is aimed at identifying increased daytime sleepiness, and testing is required to be carried out during daylight hours. Over the course of a whole day, the subject is asked to fall asleep on a bed in a darkened room 5 times. This task needs to be completed in 20 minutes. If the subject managed to fall asleep, then after 15 minutes of sleep he is woken up and asked to leave the room for two hours. If after twenty minutes you have not been able to fall asleep, you still need to leave the room and enter it after two hours. During each attempt, an electroencephalogram and electrocardiogram are taken from the study participant, and breathing and heart rate are also measured. Such a comprehensive (polysomnographic) analysis allows us to determine how long it took a person to fall asleep and what stage of sleep he was in during the next attempt.

The results for the older group were unexpected. During the test, they fell asleep as often and as quickly as the younger ones. True, the older participants themselves seemed to fall asleep faster. It turns out that 80-90 year olds experience drowsiness no more often than younger people, even if they themselves think otherwise.

Sleepiness is not the only parameter of sleep and wakefulness, and the fact that older people are no more sleepy than their grandchildren does not mean that there is no difference between the sleep of these two age categories. There are certainly differences in normal circadian rhythms between the young and the elderly. For example, in one study, two groups of healthy volunteers (18–32 years old and 60–75 years old) slept at home for a week but spent most of the day in the laboratory. Every day, the subjects noted the time when they went to bed and when they woke up. In addition, once every hour and a half, study participants had their body temperature measured, as well as the levels of cortisol and 6-sulfatoxymelatonin in their urine. Cortisol is often called the stress hormone, as it is especially released during difficult life situations. However, the intensity of its production varies throughout the day even in good conditions for the body. Most cortisol is produced in the morning immediately after waking up - at 8–9 o’clock. During the day, its level in the blood gradually decreases, although unevenly: after eating, cortisol levels temporarily increase, but not as much as in the morning. 6-sulfatoxymelatonin is a metabolic product of melatonin, the main “circadian hormone”, which is most produced in the morning shortly before waking up. By diurnal changes in the concentrations of these two hormones, one can track the course of circadian rhythms in humans (Fig. 1)

Figure 1. Daily fluctuations in the concentrations of melatonin, cortisol and somatotropin. The horizontal axis shows the time of day, and the vertical axis shows the concentration of the hormone in mg/dL (deciliter, 100 ml).

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It turned out that young subjects go to bed later, but fall asleep faster. It takes them approximately 45 minutes to fall asleep, versus the typical 95 minutes for older adults [2]. Older people sleep on average two hours less. The peak concentration of 6-sulfatoxymelatonin and cortisol in the urine in representatives of the older age group occurs earlier in the day than in younger people. However, the correlation between changes in the levels of these two hormones and the time of waking up and falling asleep in people 60–75 years old is slightly weaker than in people 18–32 years old. It turns out that in older people, the time of sleep and wakefulness shifts somewhat relative to circadian rhythms.

It is known that not only the total duration of sleep is important, but also what phases of sleep are completed during the night. Conventionally, sleep can be divided into two phases, which replace each other several times throughout the night:

• REM sleep (fast wave, paradoxical, stage of rapid eye movements - REM, rapid eye movement - REM);
• slow (non-REM sleep; divided into four stages: falling asleep, shallow sleep, deep sleep, delta sleep).

The phases differ from each other in the frequency of the electrical signal waves visible on the electroencephalogram (EEG), as well as the degree of muscle tension and the presence or absence of rapid eye movements. Both REM and non-REM sleep are important for normal well-being. Animals that were constantly artificially deprived of one of these two phases of sleep lived extremely short lives.

With age, the duration of the REM phase relative to the total sleep time decreases [3], and the proportion of the first and second stages of the non-REM phase from the total sleep time increases [4]. But the relative duration of the fourth stage, delta sleep, decreases.

REM sleep is traditionally associated with dreaming. Since the proportion of this sleep phase decreases in the elderly, the ability to remember one’s dreams should also decrease with age. In addition, dreams can be associated with autobiographical memory, and it, like other types of memory, deteriorates in old age. Both of these assumptions are confirmed by an online survey of 28,888 volunteers aged 10 to 79 years [5].

At the third stage of the non-REM sleep phase, the sigma rhythm , its second name is sleep spindles . EEG studies show that in elderly people the frequency and amplitude of sleep spindles recorded by electrodes over the frontal lobes of the cortex are reduced compared to similar indicators in young people [6]. For each EEG lead (electrode), you can build a graph of changes in the frequency of occurrence and amplitude of sleep spindles, and use it to judge the progress of aging. Probably, knowing the age-related dynamics of sleep spindles in a particular person, in the future it will be possible to identify metabolic and intellectual pathologies in him at an early stage.

Dream scenario

Sleep has two main phases: slow (orthodox, deep) and fast (paradoxical, superficial).
The slow-wave sleep phase is the beginning of night's rest; it takes up three-quarters of the total time we spend in the arms of Morpheus. Next comes the REM sleep phase, during which brain activity increases. Our body does not sleep, consciousness and subconsciousness exchange data, information is filtered, which improves our cognitive abilities. NREM sleep and the following REM sleep together constitute one cycle. It lasts for the average person about 1.5-2 hours. In total, we go through 4 to 6 cycles per night, at the end of which we should get a good night’s sleep.

It is noteworthy that slow-wave sleep becomes shorter and shorter with each new cycle, and fast sleep becomes longer. In order for the restoration of body functions to take place fully, all cycles must be completed before 4 am. After this, rest continues, but the orthodox phase no longer occurs.

You need to wake up precisely at the moment of REM sleep, since at this time all our systems are activated.

Age-related physiological changes in sleep and metabolism, as well as their disorders

Let's consider the changes in sleep physiology that manifest themselves in old age in any person without noticeable health problems. Of course, hormones and neurotransmitters, including those that are rarely heard, are involved in regulating the state of the body. Here is their list.

1. With age, the production of orexins, neuropeptides secreted by a number of hypothalamic cells, weakens (the fact is that these cells die over time). Orexins maintain a state of wakefulness, and a significant lack of orexin leads to narcolepsy - sudden attacks of irresistible sleepiness during the day. Apparently, one of the reasons why the quality of sleep in older people is worse than in younger people is lower levels of orexin [7]. The quality of sleep decreases because orexin does not simply prevent a person from falling asleep. It softens the transition between sleep and wakefulness and, one might say, makes it smoother and more predictable [8]. Agree, understanding when you fall asleep is somehow more pleasant than “switching off” suddenly or rolling your head on the pillow, waiting for Morpheus to come.
2. Adenosine is one of the non-classical mediators that cause drowsiness. Adenosine is, in fact, part of the molecule of the “universal energy currency of the cell” - ATP, only without phosphate ions and without energy-rich chemical bonds. The longer a person did not sleep, the more energy he spent, and the higher the concentration of adenosine in his blood became. You can artificially reduce the sensitivity of cells to adenosine and temporarily banish fatigue by taking its receptor antagonist, caffeine. With age, in the cerebral cortex, the balance of activity of enzymes that help synthesize adenosine and enzymes that help convert it into the form of adenosine phosphates changes: the former begin to work significantly more than the latter. Because of this, adenosine levels in the brain increase. This is probably why older people more often feel sleepy, albeit “fake” [9]. If we consider age-related changes in sleep not at the level of cells and hormones, but more globally, this is what is discovered. With age, nighttime sleep becomes fragmented, a person wakes up frequently, so the overall quality of sleep decreases, even if you go to bed for a short time during the day [10]. In fact, this is a manifestation of nighttime insomnia. Insomnia is common in older people, but increasing age alone does not increase its likelihood. It is increased by the following risk factors: depression (especially often occurs after 65), death of a spouse, retirement, onset of dementia (about dementia, see the next section). Also, the manifestations of insomnia are enhanced by alcohol and medications often used by older people: antidepressants, carbidopa and levodopa (they are prescribed for the treatment of parkinsonism), adrenaline beta blockers (for heart disease; can cause nightmares) and corticosteroids [11].
3. With insomnia and fragmented sleep, glucose metabolism may be impaired. It occurs because the concentrations of ghrelin and leptin, the “saturation hormones,” change [12], and the sensitivity of cells to the most important “glucose hormone”—insulin—changes (by the way, it also depends on circadian rhythms). Regardless of total sleep time, in people of the same age, a greater proportion of slow-wave sleep is correlated with lower body weight and a lower risk of obesity [13].

Periodic limb movements during slow-wave sleep have been linked to an increased risk of heart disease and stroke. It is only important to understand that this connection is qualitative, not quantitative. For example, it is impossible to predict by the intensity of limb movements during sleep how quickly and with what probability a person will have a stroke, because the latter can be not only a consequence of sleep pathology, but also its cause [14].

Often, health problems manifest themselves as breathing disorders during sleep: snoring, sleep apnea, etc. They appear as a consequence of disruption of the neurons of the bridge. The pons is a region of the brain where one of the “wakefulness centers” is located - the reticular formation , a collection of neurons that maintain the body’s activity in good shape, at the level of wakefulness. Not far from them is the respiratory center. Therefore, if there are problems with one group of nerve cells, the second one often suffers. Fortunately, the vast majority of patients with such problems do not experience serious breathing problems while they are awake [15].

Sensational discovery of delta sleep peptide

Long-term research in the field of dreams was crowned with success by scientists in the 70s. They were able to discover the delta sleep peptide. The donors of this substance were experimental rabbits, in whose blood it was discovered when the animals were immersed in deep sleep. If they influence the brain, it can cause the onset of deep sleep.

After such a discovery, scientists every year only find more evidence of the beneficial properties of the peptide. They are as follows:

• Defense mechanisms in the body are activated.
• Thanks to antioxidant properties, the aging process occurs at a slower rate; for example, in experimental mice, life expectancy increased by almost 25%.
• The peptide has the ability to slow down the growth of cancer tumors and suppress the formation of metastases.
• The development of dependence on alcoholic beverages is inhibited.
• Due to its anticonvulsant properties, the duration of seizures during epilepsy is reduced.
• Has an analgesic effect.

If only everyone had such a magical substance, take it in front of the bedroom door and fall into a healthy and rejuvenating sleep.

Sleep and intelligence decline in old age

Sleeping is also important because during the slow-wave and REM stages of sleep, memory consolidation —the transfer of information from short-term memory to long-term memory [16]. The hippocampus plays a key role in this process. The information that a person received while awake is “played out” several times during sleep in the form of a sequence of electrical impulses in the cells of the hippocampus, and then transmitted to the cerebral cortex (mainly the prefrontal cortex), where it remains for long-term storage. The transfer of information from the hippocampus to the prefrontal cortex during sleep is facilitated because the concentrations of cortisol and acetylcholine [17] (substances that inhibit memory consolidation) in the brain are reduced (Fig. 2).

Figure 2. Age-related changes in the activity of signaling from the hippocampus to the cerebral cortex during sleep. As we age, the proportion of slow-wave oscillations in total sleep time decreases, the prefrontal cortex gradually degrades, cortisol levels increase and acetylcholine concentrations decrease.

[18]

In old age, the process of memory consolidation occurs with less intensity [18] due to three features that were already mentioned above:

1. the share of delta sleep in total sleep time decreases;
2. cortisol production increases;
3. The structure of the prefrontal cortex changes, its volume becomes smaller with age.

However, in older people who do not suffer from serious mental and intellectual impairments, sleep is no less important for memory consolidation than for young people. For example, both of these categories of people perform the task of remembering the location of objects better after sleep. The same cannot be said for older people with cognitive problems [19].

With motor memory the situation is somewhat different. Even in healthy older adults, sleep does not improve recall of a recently learned motor skill [20]. The exact reasons for this are unknown. Perhaps the fact is that in old age, memorizing sequences of movements deteriorates in any case, and against the background of this deterioration, the “help” of sleep in the memorization processes is not noticeable.

The importance of deep sleep for the body

Many scientists have conducted research into the functions of slow-wave sleep. During the experiments, volunteers were woken up when they were sleeping the deepest. The results showed that the subjects felt muscle pain during awakening, were poorly oriented in space and time, and could not think clearly. Their cognitive and physical performance also deteriorated during the day, even if the rest of the night's rest lasted the required amount of time.

Experts have come to the conclusion that the body perceives the lack of a slow phase as a completely sleepless night. During deep sleep, organs and tissues are restored, as the pituitary gland begins to actively produce somatotropin (growth hormone).

The areas of the brain responsible for storing information also renew their resources. The longer the orthodox phase lasts, the higher the physical and mental indicators become.

However, there are also not very pleasant phenomena in this phase. If a person suffers from enuresis, talks in his sleep, or is a somnambulist, then disorders manifest themselves precisely during delta sleep. This happens for the reason that consciousness is completely switched off, replaced by the subconscious, which we cannot control.

Neurodegenerative diseases and sleep

The most common neurodegenerative diseases are Alzheimer's disease [21], [22] and Parkinson's disease. Unfortunately, their fame is sad. In Alzheimer's disease, beta-amyloid plaques accumulate in neurons, and in Parkinson's disease, Lewy bodies (alpha-synuclein) are formed in neurons. The amount of amyloid in this case correlates with sleep quality in healthy people aged 60–65 years [23]. However, it is not a fact that sleep disturbances occur due to the increased content of this protein in neurons. The opposite has also not been proven: there is no reason to claim that lack of sleep provokes Alzheimer's disease. However, sleep disturbances can potentially help diagnose Alzheimer's disease at an early stage. This is also supported by the fact that as the symptoms of this dementia intensify, the severity of sleep disorders increases (the same applies to dementia with Lewy bodies - a disease that resembles Parkinson's disease in some symptoms, and Alzheimer's disease in some others.) In addition, despite frequent naps; in patients with Alzheimer's dementia, sleep duration is significantly reduced [24].

In Parkinson's disease, sleep becomes interrupted, the REM sleep phase is disrupted, the frequency of sleep spindles and the duration of slow-wave sleep decreases, and diurnal fluctuations in cortisol levels are smoothed out. It turns out that in Parkinson's patients, sleep and wakefulness are not clearly divided into periods, the boundaries between them are to some extent blurred.

In Huntington's chorea, sleep and wakefulness are fragmented [25]. A person is active at night and falls asleep late. He has a reduced proportion of REM sleep, an increased frequency of sleep spindles, and during stage 1 non-REM sleep, chorea can be observed - chaotic uncontrolled movements of the limbs, the main manifestation of this disease during wakefulness.

With ALS (amyotrophic lateral sclerosis), breathing disorders occur during sleep. REM sleep becomes intermittent, and the proportion of slow-wave sleep decreases. In addition, the course of daily fluctuations in cortisol is disrupted.

Interestingly, the manifestation of almost all of the above sleep disorders can be weakened with the help of phototherapy (periodic exposure to bright light) and organized (not uncontrolled!) melatonin intake.
Table 1. Summary table of associations of the most common sleep disorders with neurodegenerative diseases.

In conclusion

Slow-wave sleep is very important for humans, as it is responsible for restoring physical performance, the immune system and cognitive abilities. It is also necessary to maintain youth, since it is in the orthodox phase that skin cells are renewed.

You need to fall asleep at 21.00-22.00 in order to get your “portion” of deep sleep and get quality rest during the night. If you follow the schedule, you will notice within 2 weeks how your well-being and appearance will improve.

Author: Dasha Pashchenko

What happens during delta sleep

Without the use of special equipment, it is difficult to find out what happens during the delta stage of sleep. People awakened during this period usually answer that they don’t understand anything and haven’t seen any dreams. When trying to analyze their condition, they noted the absence of thoughts and sensations.

In fact, everything happens the other way around. A slowdown in physiological and psychological processes occurs at the stage of falling asleep. When entering the delta sleep state, these processes begin to activate:

• the heart rate increases (by the end of the stage it reaches maximum levels);
• The galvanic skin reaction intensifies (during this period it corresponds to a state of strong excitement).

How long should deep sleep last?

All phases and stages of sleep have their own duration. It is not fixed and changes depending on the cycle. Deep sleep in the first cycle lasts about 100 minutes, in cycles 4 and 5 it is reduced to a minimum. In some cases, it falls out of the sequential series of stages altogether.

The duration of deep sleep depends on a person’s age and has its own norms. When they are violated, the body does not rest and experiences severe stress.

Normal for an adult

Experimental work has determined the average time indicators for deep sleep, allowing the body to fully recover. For a healthy adult they were:

• 120 minutes for young people under 30 years of age;
• 85 minutes for people under 55-60 years old;
• 80 minutes for pensioners over 60 years of age

Normal for a child

The deep sleep stage is directly related to brain development. In newborns it is not developed, so they do not have this stage. It is replaced by “restful sleep.” By three months, brain activity begins to activate, and the stage of deep sleep appears in the slow phase.

At first it is not long - about 20 minutes. Gradually it begins to increase.

What time should you go to bed or wake up to feel alert during the day? The optimal time and possible duration of sleep will help you calculate the sleep calculator