Many interesting studies have been conducted in the field of sleep medicine. You can check out the journal Sleep Medicine and the website of the American Academy of Sleep Medicine. However, the exact roles of sleep and the relationship of sleep to longevity are not well understood. Most studies in the literature appear to have to do with sleep deprivation, sleep disorders like insomnia or restless legs syndrome or the relationship of sleep to certain diseases like diabetes and immune system disorders. This blog entry offers a brief general introduction to the roles of sleep and then focuses on a few studies that relate amount of sleep to general health and longevity.
Roles of sleep
Sleep is a very multifaceted subject. A number of interesting talks from a 2007 conference on sleep at the Salk Institute, Waking up to Sleep can be found here. Particularly, Jerry Siegel’s talk provides a general introduction to the topic. In many species of animals, including ourselves, dogs, cats and primates, evolution has given a high priority to sleeping, so it must fulfill important survival needs. Whatever sleep does, it is known that prolonged sleep deprivation or abnormal sleep can have serious consequences. In rats, prolonged sleep deprivation can lead to a physical damage including skin lesions, subcortical damage, weight loss, blood plasma changes and slowed wound healing(ref). In humans, sleep deprivation appears to be associated with decreased cognitive function(ref), psychotic-like states(ref) and other negative situations reported below.
About 20 species are known to sleep like we do, a small percentage of those out there. And whether or how animals sleep in thousands of other species has not been systematically studied.
Sleep is complicated, typically consisting of several phases. “REM (rapid eye movement) sleep in adult humans typically occupies 20–25% of total sleep, about 90–120 minutes of a night’s sleep. During a normal night of sleep, humans usually experience about four or five periods of REM sleep; they are quite short at the beginning of the night and longer toward the end. Many animals and some people tend to wake, or experience a period of very light sleep, for a short time immediately after a bout of REM. The relative amount of REM sleep varies considerably with age. A newborn baby spends more than 80% of total sleep time in REM. During REM, the activity of the brain’s neurons is quite similar to that during waking hours, but the body is paralyzed due to atonia; for this reason, the REM-sleep stage may be called paradoxical sleep. This means there are no dominating brain waves during REM sleep. — REM sleep is physiologically different from the other phases of sleep, which are collectively referred to as non-REM sleep (NREM). Vividly recalled dreams mostly occur during REM sleep(ref).” REM sleep is a state in which the brain stem is highly activated, brain metabolism is high and in which twitching and male erections sometimes occur. The brain is doing some kind of work during REM sleep. REM sleep does not occur in fish, reptiles and insects but does appear to occur in some mammal species in addition to humans.
Needs for sleep and optimal sleep patterns may vary from individual to individual. “Sleep is a complex phenotype and as such it is possible that there are numerous genes which may each have a number of effects that control an individual’s sleep pattern(ref).” Truthfully, there is very much we don’t know about it.
The various roles of sleep in normal and pathological conditions is the subject of much study and discussion but is relatively ill-understood. One role of sleep that is fairly well agreed-on is memory consolidation(ref). “– converging evidence, from the molecular to the phenomenological, leaves little doubt that offline memory reprocessing during sleep is an important component of how our memories are formed and ultimately shaped(ref).” However details of this process and exactly what happens during sleep remain murky. “–the term ‘‘memory consolidation’’ refers to a poorly defined set of processes which take an initial, unstable memory representation and convert it into a form that is both more stable and more effective. At this time, it is unclear how memories are altered after initial encoding, and no consensus as to which of the processes contributing to this alteration should be included under the umbrella of memory consolidation(ref).
Sleep – how many hours are best?
Many studies have sought to correlate the average number of hours spent daily in sleeping with mortality for individuals in various populations and in different age and gender categories. The studies point to somewhat inconsistent but interesting results.
Recent population studies
To begin, the 2010 publication Sleep Duration and All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Studies analyzes the results of 16 studies which included “– 27 independent cohort samples. They included 1,382,999 male and female participants (follow-up range 4 to 25 years), and 112,566 deaths. Sleep duration was assessed by questionnaire and outcome through death certification. In the pooled analysis, short duration of sleep was associated with a greater risk of death (RR: 1.12; 95% CI 1.06 to 1.18; P < 0. 01) with no evidence of publication bias (P = 0.74) but heterogeneity between studies (P = 0.02). Long duration of sleep was also associated with a greater risk of death (1.30; [1.22 to 1.38]; P < 0.0001) with no evidence of publication bias (P = 0.18) but significant heterogeneity between studies (P < 0.0001).”
— “Short duration of sleep was defined differently in different studies. It: “was ≤5 h per night,6,7,20,22 ≤6 h,10,19,23,25 <7 h,21,24,26–29 ≤4 h.9” The studies likewise defined long duration of sleep differently > 8 h per night,10,19,24,30 ≥9 h,6,7,20,22,23,25–28 ≥10 h,9,21 and ≥ 12h.29 And “the reference category, being 7 h per night in the majority of studies,6,7,9,19–22 7 to 8 h,23–26 7 to 9 h,27,28 6 to 8 h,10 and 9 h.29” Therefore, since “short” and “long” are variably-defined, the exact meaning of the conclusion of this meta study is not clear “Both short and long duration of sleep are significant predictors of death in prospective population studies.” I would take it to mean something like “Less than 5.5 hours of sleep per night or more than 9 hours are significant predictors of death in prospective population studies”
A new study reported in an October issue of Science Daily, Women’s Study Finds Longevity Means Getting Just Enough Sleep contributes another piece to the puzzle that may not exactly fit with the rest. “A new study, derived from novel sleep research conducted by University of California, San Diego researchers 14 years earlier, suggests that the secret to a long life may come with just enough sleep. Less than five hours a night is probably not enough; eight hours is probably too much. — A team of scientists, headed by Daniel F. Kripke, MD, professor emeritus of psychiatry at UC San Diego School of Medicine, revisited original research conducted between 1995 and 1999. In that earlier study, part of the Women’s Health Initiative, Kripke and colleagues had monitored 459 women living in San Diego (ranging in age from 50 to 81) to determine if sleep duration could be associated with mortality.”
“Fourteen years later, they returned to see who was still alive and well. — Of the original participants, 444 were located and evaluated. Eighty-six women had died. Previous studies, based upon questionnaires of people’s sleep habits, had posited that sleeping 6.5 to 7.5 hours per night was associated with best survival. Kripke and colleagues, whose 1990s research had used wrist activity monitors to record sleep durations, essentially confirmed those findings, but with a twist. — “The surprise was that when sleep was measured objectively, the best survival was observed among women who slept 5 to 6.5 hours,” Kripke said. “Women who slept less than five hours a night or more than 6.5 hours were less likely to be alive at the 14-year follow-up. — Kripke said the study should allay some people’s fears that they’re not getting enough sleep. “This means that women who sleep as little as five to six-and-a-half hours have nothing to worry about since that amount of sleep is evidently consistent with excellent survival. That is actually about the average measured sleep duration for San Diego women.”
This UC study has a consistent result with the above-mentioned 2010 metastudy Sleep Duration and All-Cause Mortality: A Systematic Review and Meta-Analysis of Prospective Studies in that too much or too little sleep increases mortality. However, the amount of nightly sleep corresponding to the lowest mortality – 5 to 6.5 hours – seems to be surprisingly low in this UC study when compared to the least mortality ranges in the meta-study or when compared to other studies or conventional wisdom.
A large study in China is reported in the 2010 publication STUDY OBJECTIVES: To examine factors associated with self-reported sleep quality and duration among very old adults in China. — DESIGN: Cross-sectional analysis of the 2005 wave of the Chinese Longitudinal Healthy Longevity Survey (CLHLS). — SETTING: In-home interview with older adults in 22 provinces in mainland China. — PARTICIPANTS: A total of 15,638 individuals aged 65 and older (5,047 aged 65-79, 3870 aged 80-89, 3927 aged 90-99, and 2794 aged 100 and older, including 6688 men and 8950 women). — Sixty-five per cent of Chinese elders reported good quality of sleep. The average number of self-reported hours of sleep was 7.5 (SD 1.9), with 13.1%, 16.2%, 18.0%, 28.0%, 9.2%, and 15.5% reporting < or = 5, 6, 7, 8, 9, and > or =10 hours, respectively (weighted). Multivariate analyses showed that male gender, rural residence, Han ethnicity, higher socioeconomic status, and good health conditions were positively associated with good quality of sleep. All other factors being equal, octogenarians, nonagenarians, and centenarians were more likely to have good sleep quality than the young elders aged 65-79. Elders with poorer health status or older age were more likely to have either relatively shorter (< or = 6 h) or longer (> or = 10 h) sleep duration. Married elders were more likely to have an average duration between these two values. Except for some geographic variations, associations between all other factors and sleep duration were weak compared to the effects of health. — CONCLUSIONS: Age and health conditions are the two most important factors associated with self-reported sleep quality and duration. Good quality of sleep among long-lived old adults may have some implications for achieving healthy longevity.”
A series of recent news reports are appearing sharing some of the new findings, like The perils of too much sleep. “10 Hours Or More May Increase Stroke Risk, Researchers Say. — Women who get more than 10 hours of sleep a night may increase their risk of incident stroke, researchers said here at the American Heart Association meeting. Additionally, women who had six or less hours of sleep did not have an associated increased stroke risk, Dr. Alan Flint of the Harvard School of Public Health reported. — Flint and colleagues performed a prospective cohort study of 69,794 female nurses ages 40 to 65, measuring self-reported sleep data from 1986 to 2006 to an endpoint of fatal or nonfatal stroke. — Patients were asked to report total hours of actual sleep — ranging from less than five to 11 or more — as well as any confounding factors, such as alcohol intake, fruit and vegetable consumption, physical activity, and smoking status. Body mass index and the presence of diabetes or hypertension were recorded as potential intermediary factors. — At the 20-year follow-up, a total of 2,303 strokes were reported. After adjusting for confounders, Flint and colleagues found those who had slept 10 or more hours a night had a 63 percent increased risk of stroke compared with a baseline average risk with seven hours a night of sleep.
Comparatively, patients who slept six or fewer, or from eight to nine hours a night, had insignificant increases in stroke risk after adjusting for confounders, when compared with baseline. Researchers were unable to determine any of the underlying biological mechanisms that may cause the increased risk in patients with higher sleep duration. “We do find that identifying long sleep duration is useful in marking risk, although it doesn’t immediately lead to any clinical recommendation,” Flint told MedPage Today. Future research should investigate the possible causes of the increased risk of stroke in women, he said. “We’d like to update [the study] and get an idea of whether a pattern of sleep over a lifetime that accounts for the risk, or whether there are other factors that account for that, like clinical depression, jobs, family, or other interaction with that risk.”
Correlations of sleep lengths and quality with pathological conditions
A November 15 news release Poor Sleep Quality Increases Inflammation, Community Study Finds reports “People who sleep poorly or do not get enough sleep have higher levels of inflammation, a risk factor for heart disease and stroke, researchers have found. — Data from a recent study were presented Sunday, Nov. 14 at the American Heart Association Scientific Sessions in Chicago by Alanna Morris, MD, a cardiology fellow at Emory University School of Medicine. –The results come from surveying 525 middle-aged people participating in the Morehouse-Emory Partnership to Eliminate Cardiovascular Health Disparities (META-Health) study on their sleep quality and sleep duration. — Acute sleep deprivation leads to an increased production of inflammatory hormones and changes in blood vessel function, but more research is needed on the physiological effects of chronic lack of sleep, Morris says.– “Most of the studies looking at the body’s response to lack of sleep have looked at subjects who have been acutely sleep deprived for more than 24 hours in experimental sleep laboratories,” she says. “Nothing of this sort has been investigated in epidemiologic studies.” — In the META-Health study, the researchers assessed sleep quality using the Pittsburgh Sleep Quality Index survey, where a score over six (based on the median sleep score of the study population) is considered poor. They also analyzed their data based on hours of sleep. –Individuals who reported six or fewer hours of sleep had higher levels of three inflammatory markers: fibrinogen, IL-6 and C-reactive protein. In particular, average C-reactive protein levels were about 25 percent higher (2 milligrams per liter compared to 1.6) in people who reported fewer than six hours of sleep, compared to those reporting between six and nine hours.– That difference was still significant even when the data is corrected for known risk factors such as smoking, blood pressure, diabetes and obesity, Morris says. –“
“For people who got little sleep, the C-reactive protein levels were increased, but still in the range of what health authorities would consider low to intermediate risk,” she says. “However, our study population represents a community-based population [as opposed to patients in the hospital or with known cardiovascular disease], so they have overall lower risk and lower C-reactive protein levels than many of the high risk populations in other studies.” — Inflammation may be one way poor sleep quality increases the risks for heart disease and stroke, Morris says.– “It remains uncertain whether short sleep duration contributes directly to cardiovascular mortality, or whether it is a mediating or moderating factor,” she says.–Previous research has shown that people who sleep between seven and eight hours per night live longest, and that especially short or especially long sleep durations bring higher mortality. Researchers find that short and long sleep durations are often seen together with high blood pressure, obesity, diabetes and psychological stress – all risk factors for heart disease and stroke. — Long sleep duration may reflect a compensation for sleep apnea, which the sleep quality survey does not directly address. However, in the META-Health study, people who slept for more than nine hours didn’t show significantly higher levels of inflammation markers. — In a separate poster, Morris is also presenting research on a difference between men and women in the interaction between sleep quality and arterial stiffness. Her results show that both men and women with poor sleep quality had higher blood pressures, but only men with poor sleep quality had a higher arterial stiffness, a lack of blood vessel flexibility which drives hypertension and puts more burden on the heart.”
I point out that in this study and others, correlations between sleep quality and sleep lengths with health factors like inflammation and presence of C-reactive protein do not establish causation in either direction.
The relationship between abnormal sleep durations and potential cardiovascular and other problems has been noted before, for example in the 2007 publication Review: Inflammation, sleep, obesity and cardiovascular disease. “Sleep loss can also have consequences on safety related behaviours both for the individuals and for the society, for example the increased risk of accidents when driving while drowsy. In this case there might appear to be a causal chain. Accidents don’t create prior sleep loss and drowsiness. However, other factors besides sleep loss could lead to both lack of sleep and accident proneness, such as intense emotional stress.
While conventional wisdom holds that amount of sleep is correlated with cognitive functioning, this may not necessarily be the case. For example the 2006 publication Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures concludes “Objectively measured disturbed sleep was consistently related to poorer cognition, whereas total sleep time was not. This finding may suggest that it is disturbance of sleep rather than quantity that affects cognition.” “Results are from 2932 women (mean age 83.5 years) in the Study of Osteoporotic Fractures between 2002 and 2004. Cognitive function was measured by Mini-Mental State Examination (MMSE) and Trail Making B Test (Trails B). Cognitive impairment was defined as MMSE < 26 or Trails B > 278 seconds. Sleep parameters measured objectively using actigraphy included total sleep time, sleep efficiency, sleep latency, wake after sleep onset (WASO), and total nap time.”
Inadequate sleep has also been thought to affect glucose metabolism and raise the risk for diabetes. Example publications addressing these issues are the 2009 publication Do sleep disorders and associated treatments impact glucose metabolism?, the 2008 report The reciprocal interaction between sleep and type 2 diabetes mellitus: facts and perspectives and the 2005 study Sleep loss and the development of diabetes: a review of current evidence. “Emerging evidence suggests that short duration of sleep and sleep disturbances increase the risk of developing diabetes.”
The association of too-short or abnormal sleep with overproduction of inflammatory cytokines is a repeated theme in the research literature. For example, the 2005 publication Experimental studies on the interaction between sleep and the immune system in humans reports on the causative effect of inflammatory cytokines on sleep. “Sleep-wake behavior is very sensitive to experimental host defense activation, for example, by bacterial endotoxin. When the injection of endotoxin is accompanied by fever and a prominent neuroendocrine activation, sleep continuity will be disturbed. When the production of inflammatory cytokines is stimulated by smaller amounts of endotoxin, but no fever and no neuroendocrine activation are apparent, the nonREM-sleep amount will increase. This is possibly due to changes in the biological activity of the tumor necrosis factor-alpha (TNF-alpha) system. Besides their important function in sleep regulation during acute immune response, cytokines also seem to be involved in physiological sleep regulation, although there still is not very much data on this issue.”
In fact, the communication between the brain and the immune system with respect to sleep seems to flow both ways as pointed out in the 2006 report Bidirectional communication between the brain and the immune system: implications for physiological sleep and disorders with disrupted sleep.
The 2008 publication Sleep, insomnia and falls in elderly patients Points out the difficulty of interpreting sleep data. Do old patients who have insomnia fall and experience fractures because of lack of sleep or because of their medications? “Insomnia is common in older people and can be associated with significant daytime dysfunction. Sleep problems, and the medications used to treat them, may contribute to the risk of falls and fractures in this population; however, the independent effects of disturbed sleep or the risk of hypnotic use are not well understood.”
The 2008 study report Actigraphy-measured sleep characteristics and risk of falls in older women comes up with a somewhat clear result. “METHODS: Study subjects were participants in the Study of Osteoporotic Fractures. In 2978 primarily community-dwelling women 70 years and older (mean age, 84 years), sleep and daytime inactivity were estimated using wrist actigraphy data collected for a minimum of 3 consecutive 24-hour periods (mean duration, 86.3 hours). Fall frequency during the subsequent year was ascertained by a triannual questionnaire. Use of medications was obtained by examiner interview. — RESULTS: In multivariate-adjusted models, relative to those with “normal” nighttime sleep duration (>7 to 8 hours per night), the odds of having 2 or more falls in the subsequent year was elevated for women who slept 5 hours or less per night (odds ratio, 1.52; 95% confidence interval, 1.03-2.24). This association was not explained by the use of benzodiazepines. Indexes of sleep fragmentation were also associated with an increased risk of falls. For example, women with poor sleep efficiency (<70% of time in bed spent sleeping) had 1.36-fold increased odds of falling compared with others (odds ratio, 1.36; 95% confidence interval, 1.07-1.74).” In this study 5 hours or less of sleep per night correlated with increased risk for falls, while the new UC study described above suggests that the lowest mortality for women is associated with 5 – 6.5 hours of sleep.
These are but a sample of a large collection of publications implicating disease and pathology associations with abnormal sleep conditions. For purposes here, the main take-away message is that a number of pathological conditions are associated with insufficient or disturbed sleep. Many researchers are content to see this as an association. Other researchers see a causal connection. They see insufficient or disturbed sleep as causing a pathological condition.
Diet and sleep
Diet too seems to be a factor with respect to sleep. The 2009 publication Relationships among dietary nutrients and subjective sleep, objective sleep, and napping in women particularly implicates the intake of dietary fats with shortening of sleep time. “Participants were 459 post-menopausal women enrolled in the Women’s Health Initiative. Objective sleep was estimated using one week of actigraphy. Subjective sleep was prospectively estimated with a daily sleep diary. — CONCLUSIONS: Actigraphic total sleep time was negatively associated with intake of fats. Subjective napping, which may be a proxy for subjective sleepiness, was significantly related to fat intake as well as intake of meat.”
There is probably much more that can be said about diet and sleep and I will possibly take that topic up in another blog post.
No causative effects determined
Note that in all of these studies there are correlations of lengths of sleep time or quality of sleep with mortality or pathological conditions, but not causative links. For example, yes “those who had slept 10 or more hours a night had a 63 percent increased risk of stroke compared with a baseline average risk with seven hours a night of sleep.” But the long sleeping times may not have caused the increased risk of stroke. Some underlying illnesses may have both induced the longer sleeping times and the increased risk of strokes. Yet, some researchers have inferred the presence of causation which seems sensible to them.
What I get from all of the above is:
· Much is yet to be learned about the relationships between sleep, health and longevity.
· Multiple population studies indicate longevity is correlated with not too-much and not too-little sleep. However the studies are inconsistent in defining “too much” and “too little” sleep. Somewhere between 5.5 and 7 hours of sleep a night is the average sweet-spot depending on the study.
· Multiple pathological states appear to be correlated with too-little or too-much sleep. Again, the definitions of too-little or too-much sleep vary according to the study.
· The population studies establish only correlations, not that amount of sleep increases or decreases mortality or any health risk. Certain sicknesses could lead to health hazards and at the same time either interfere with sleep or lead to prolonged sleeping.
· However some researchers infer that there is a causal connection where sleep duration and quality is a determinant of longevity or health conditions.
· The population studies provide averages but do not establish that “one size fits all” with respect to sleeping durations. Optimum length of nightly sleeping time is likely to vary among individuals.
· Personally, I typically enjoy between 7.5 and 9 hours of sleep a night, relatively long times for my age group. According to some studies this is fine. According to other studies so much sleep puts me in a higher-mortality risk category.