Sleep and Aging II

What is the difference between the sleep of the elderly and the sick from the sleep of the young and healthy?

Svetlana Yastrebova, Biomolecule

In the last part, we talked about what circadian rhythms are, what genes they are provided with, and how mutations of these circadian genes can affect health. Well, sleep disorders cannot but affect the course of circadian rhythms. Of course, sleep disorders do not occur by themselves. These are almost always manifestations of some other painful processes in the body. Such processes may include malfunctions of internal organs, and cognitive disorders. At the same time, a number of diseases that are often observed with sleep problems are also detected in the elderly. A coincidence? Not necessarily at all.

Sleep can be called the main event of the day. If we eat a couple of hours later or earlier than the prescribed regime, we will not feel as bad as if we fall asleep a couple of hours later or earlier.
The inability to fall asleep on time is not always caused by the carelessness of a single person, and the situation does not turn out to be quickly and easily corrected every time.
Sleep disorders, fragmented sleep, morning and afternoon drowsiness – all this can be a sign of a hidden disease. Drawing from the website flickr.com .

Circadian rhythms, and with them sleep, can be disrupted by anyone. It's enough to stay up late at the computer or fly a couple thousand kilometers from east to west (or vice versa). A little earlier we talked about the fact that mutations in the "genes of the internal clock" (and hence sleep disorders) lead to problems with metabolism and, ultimately, can cause a variety of diseases. Interestingly, older people have both sleep disorders and metabolic disorders at the same time. Most likely, it has something to do with it.

The truth and myths about the sleep of the elderly

Older people often note daytime sleepiness, and therefore it is believed that they have a disturbed night's sleep. 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 the elderly only think that they experience drowsiness more often and more strongly than young people [1].

The participants passed 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 on it is mandatory during daylight hours. During the whole day, the subject is offered 5 times to fall asleep on a bed in a darkened room. 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 it was not possible to fall asleep, you still need to leave the room and enter it in two hours. During each attempt, an electroencephalogram and an electrocardiogram are taken from the study participant, as well as the respiratory rate and heartbeat are measured. Such a complex (polysomnographic) analysis allows you to identify how long it took a person to fall asleep, and at what stage of sleep he was 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 young ones. However, the elderly participants themselves seemed to fall asleep faster. It turns out that 80-90-year-olds experience drowsiness no more often than young people, even if they themselves think otherwise.

Drowsiness is not the only parameter of sleep and wakefulness, and the fact that old people actually want to sleep no more often 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 in 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, the study participants were measured body temperature, as well as the content of cortisol and 6-sulfatoxymelatonin in the urine. Cortisol is often called a stress hormone, as it is especially released in difficult life situations. Nevertheless, the intensity of its production and in good conditions for the body varies throughout the day. Most of all cortisol is formed in the morning immediately after waking up – at 8-9 hours. During the day, its content in the blood gradually decreases, although unevenly: after eating, the cortisol level temporarily rises, but not as much as in the morning. 6-sulfatoxymelatonin is a product of melatonin metabolism, the main "circadian hormone", which is most formed in the morning shortly before waking up. According to the daily change in the concentration of these two hormones, it is possible to track the course of circadian rhythms in humans (Fig. 1)

Figure 1. Daily fluctuations in melatonin, cortisol and somatotropin concentrations. On the horizontal axis, the time of day is postponed, on the vertical – the concentration of the hormone in mg / dl (deciliter, 100 ml).
Drawing from the website usdbiology.com .

It turned out that young subjects go to bed later, but fall asleep faster. It takes them about 45 minutes to fall asleep, compared to the 95 minutes usual for the elderly [2]. The elderly sleep an average of two hours less. The peak concentration of 6-sulfatoxymelatonin and cortisol in the urine in the older age group occurs earlier in the time of day than in the young. However, the correlation between the change in the content of these two hormones and the time of waking up and falling asleep in people aged 60-75 years is slightly weaker than in people aged 18-32 years. It turns out that in the elderly, 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 it have time to pass during the night. Conventionally, sleep can be divided into two phases, which replace each other several times during the night:

1. fast sleep (fast–wave, paradoxical, stage of rapid eye movements - REM, rapid eye movement – REM);

2. 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 waves of electrical signals 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 did not live very long.

With age, the duration of the REM phase decreases relative to the entire sleep time [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, is decreasing.

REM sleep is traditionally associated with dreams. Since the proportion of this phase of sleep in the elderly decreases, then the ability to remember their dreams should 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 phase of sleep, the sigma rhythm is visible on the electroencephalogram, its second name is sleep spindles. EEG studies show that in elderly people, the frequency and amplitude of carotid spindles recorded by electrodes over the frontal lobes of the cortex decrease compared to similar indicators in young people [6]. For each EEG lead (electrode), it is possible to plot changes in the frequency of occurrence and amplitude of carotid spindles, and judge the course of aging by it. Probably, knowing the age dynamics of sleepy spindles in a particular person, in the future it will be possible to identify pathologies of metabolism and intelligence at an early stage.

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

Consider the changes in sleep physiology that occur in old age in any person without noticeable health problems. Of course, hormones and neurotransmitters are involved in the regulation of the state of the body, including those that are rarely heard. Here is their list.

With age, the production of orexins – neuropeptides secreted by a number of hypothalamic cells weakens (the fact is that these cells die off over time). Orexins maintain a state of wakefulness, and a significant lack of orexin leads to narcolepsy – sudden attacks of irresistible drowsiness during the day. Apparently, one of the reasons why the quality of sleep in older people is worse than in young people is a lower content of orexin [7]. The quality of sleep decreases because orexin does not just 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, it's somehow nicer to understand when you fall asleep than to "turn off" suddenly or roll your head on the pillow, waiting for the arrival of Morpheus.

Adenosine is one of the non–classical mediators that cause a state of 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. It is possible to artificially reduce the sensitivity of cells to adenosine and temporarily banish fatigue by taking an antagonist of its receptors – caffeine. With age, the balance of activity of enzymes helping to synthesize adenosine and enzymes helping to convert it into the form of adenosine phosphates changes in the cerebral cortex: the former begin to work significantly more than the latter. Because of this, the level of adenosine in the brain increases. This is probably why the elderly often feel drowsiness, even if it is "not real" [9].

If we consider age-related changes in sleep not at the level of cells and hormones, but more globally, we find this. With age, night sleep becomes fragmented, a person often wakes up, 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 nocturnal insomnia.

Insomnia is often found in the elderly, but great age alone does not increase its likelihood. It is increased by such risk factors: depression (especially often occurs after 65), the death of a spouse, retirement, the onset of manifestations of dementia (about dementia, see the next section). Also, the manifestations of insomnia are enhanced by alcohol and medications often used by the elderly: antidepressants, carbidopa and levodopa (they are prescribed for the treatment of parkinsonism), adrenaline beta-blockers (for heart disease; can cause nightmares) and corticosteroids [11].

With insomnia and fragmentary sleep, a violation of glucose metabolism is possible. It occurs because the concentrations of ghrelin and leptin, the "saturation hormones", change [12], as well as the sensitivity of cells to the most important "glucose hormone" – insulin (by the way, it also depends on circadian rhythms). Regardless of the total sleep time in people of the same age, a large proportion of slow-wave sleep correlates with a lower body weight and a lower risk of obesity [13].

Periodic limb movements during slow sleep are associated with an increased risk of cardiovascular diseases and stroke. It is only important to understand that this relationship 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 may 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 bridge neurons. The bridge is a part of the brain where one of the "centers of wakefulness" is located – the reticular formation, a cluster of neurons that support the activity of the body in tone, at the level of wakefulness. There is a breathing center not far from them. Therefore, with problems with one group of nerve cells, the second often suffers. Fortunately, during wakefulness, the vast majority of patients with such problems do not show serious respiratory disorders [15].

Sleep and deterioration of intelligence in old age

It is also important to sleep because during the slow-wave stage and the REM stage of sleep, memory consolidation occurs – 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" several times in a dream in the form of a sequence of electrical impulses in the cells of the hippocampus, and then transmitted to the cerebral cortex (mainly to the prefrontal), 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 change in the activity of signal transmission from the hippocampus to the cerebral cortex during sleep. As we age, the proportion of slow-wave oscillations in the total sleep time decreases, the prefrontal cortex gradually degrades, cortisol levels increase and the concentration of acetylcholine decreases. Figure from [18].

In old age, the process of memory consolidation is less intense [18] due to three features that have already been 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.

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

With motor memory, the situation is somewhat different. Even for healthy elderly people, sleep does not help to remember a recently learned motor skill better [20]. The exact reasons for this are unknown. Perhaps the fact is that in old age, memorization of sequences of movements worsens in any case, and against the background of this deterioration, the "help" of sleep in the processes of memorization is not noticeable.

Neurodegenerative diseases and sleep

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

In Parkinson's disease, sleep becomes intermittent, the REM phase of sleep is disrupted, the frequency of sleep spindles and the duration of slow-wave sleep decreases, and daily fluctuations in cortisol levels are smoothed out. It turns out that in Parkinsonists, sleep and wakefulness are indistinctly divided into periods, the boundaries between them are to some extent erased.

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

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 of cortisol is disrupted.

Interestingly, the manifestation of almost all of the above sleep disorders can be weakened with the help of phototherapy (periodic irradiation with bright light) and organized (not uncontrolled!) taking melatonin.

So, circadian rhythms and sleep are inextricably linked with aging and all its accompanying attributes. Probably someday, by influencing one thing, we will be able to change another: for example, we will cure sleep problems in a person suffering from a neurodegenerative disease, and his level of intelligence will stop decreasing, thereby prolonging his active life. Maybe someday we will be able to reduce the negative impact of lack of sleep on the likelihood of getting cancer and we will have more time without the risk of dying from cancer problems. At worst, we will recognize Alzheimer's disease or Huntington's chorea in the early stages by violations of fast-wave and slow-wave sleep. Everything that is studied for human health is for the best.

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Portal "Eternal youth" http://vechnayamolodost.ru 29.02.2015