ASCANIO POLIMENI M.D. NEUROENDOCRINOLOGIST CONDIRECTOR of REGENERA RESEARCH GROUP. Sleep,Hormones, Immunity, Longevity and Successful Aging

Transcription

1 ASCANIO POLIMENI M.D. NEUROENDOCRINOLOGIST CONDIRECTOR of REGENERA RESEARCH GROUP Sleep,Hormones, Immunity, Longevity and Successful Aging

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3 Health-Disease

4 We are What We: Think Eat Drink Feel Breath

5 We are also.. How We: SLEEP SLEEP is an essential a component as Good Nutrition,Water,Air and Exercise to Optimal Health, to our Mental-Physical Performances and to Quality of Life

6 Stages REM REM REM REM REM The Sleep Cycle in Adults Awake Hours in Sleep

7 Functions of Sleep: -Why do we sleep for 1/3 of our life? -What are some of the functions of sleep? 1.Memory Consolidation 2.Energy Conservation 3.Body-Brain Restoration 4.Immune-Endocrine System Regulation

8 Relationship between sleep, circadian rhythm, and the neuroendocrine, autonomic nervous and immune systems. Changes in the immune system cause changes in sleep and, conversely, sleep has an important role in restoring the immune system or sleep loss alters immune s.

9 Sleep influences circadian alternance between TH1-TH2 immune system branches TH1 TH2 MLT GHRH-GH PRL NONREM SWS REM CRH ACTH CORTISOLO

10 Putative pathways of immune system involvement in sleep. In general, pro-inflammatory cytokines induce sleep, whereas anti-inflammatory cytokines inhibit sleep.

11 MLT LEPTIN GHRL PRL TEST. GHRH-GH SS CRH-ACTH CORT. TSH CYTOKINES FSH-LH SLEEP HORMONES SEX HORMONES PRL NPY GALANIN ACTH-CRH CORT. GHRH-GH SS CYTOKINES MLT VASOPRESSIN THYR.HORM.

12 Stages REM REM REM REM REM The Sleep Cycle in Adults Awake Hours in Sleep

13 Sleep Hormones different hormones are produced mainly during Sleep Melatonin(1 PART) Ghrh-GH(1 PART SWS) Leptin(1 PART) Ghrelin(1 PART SWS) Testosterone(1-2 PART) Prolactin(MIDDLE-2 PART) TH-1 Cytochynes(1 PART) TH2 Cytochynes(2 PART) CRH-ACTH-CORT-SOMATOSTATIN (2 PART-MORINING HOURS)-

14 % of the total 24 h * * * PLASMA MELATONIN CIRCADIAN RHYTHM DAY / NIGHT amt6s URINARY EXCRETION pg/ml 70 (x ± SEM) L/D Population mean cosinor summary p % Rhythm MESOR M AMPLITUDE A (x ± SEM) (x ± SEM) ACROPHASEØ (95% c.l.) ( ) hours day night *** p <.001 YOUNG CONTR ± ± ' 01:30 (n=15) (-04 05' to ') (00:16 to 03:08)

15 MELATONIN RHYTHM AS ENDOGENOUS SYNCHRONIZER FOR OTHER RHYTHMS Pineal gland Light / Dark SCN h Melatonin h Temperature h Sleep / Wakefulness h Cortisol Circadian rhythms

16 CIRCADIAN RHYTHM OF MLT CORTISOL GH INSULIN-ADIPONECTIN LEPTIN-GHRELIN FSH-LH T4 T3

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18 REM NONREM SWS MLT GHRH-GH CRH ACTH CORTISOLO SS

19 INTERACTION LEPTIN - NPY Hypothalamic NPY - food intake BAT activity insulin secretion LEPTIN FAT MASS

20 Twenty-four-hour profiles of rapidly sampled plasma ghrelin (a) and adiponectin (b) in lean (blue) and obese (red) male subjects Yildiz B O et al. PNAS 2004;101: by National Academy of Sciences

21 TEST??

22 Hormones Sleep A number of hormones are known to modify sleep and sleep propensity Sleep inducing hormones Sleep reducing hormones Delta Sleep Inducing Hormone Vasoactive intestinal peptide Growth Hormone Releas. Fact. Ghrelin-Prolactin Growth hormone Insulin Melatonin Progesterone Estradiol Oxytocin Th-1 cytokines Vasopressin-NPY-Galanin ACTH-CRH Cortisol-Catecholamines Pregnenolone Somatostatin Thyreotropin releasing hormone(t3-t4) Endorphine Prostaglandine E Th2-cytokines

23 Melatonin & Sleep

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25 MLT in the elderly people Elderly people who are good sleepers had higher mlt levels than those with insomnia. Elderly produce less mlt and present altered mlt rhythm (begin produce it earlier at night and stop producing it earlier in the morning.- PHASE ADVANCED ). Older people show a disruption in the normal stage of sleep.they get less priority sleep (REM and stage III and IV).

26 Significantly lower serum melatonin in patients with chronic primary insomnia Chronic insomnia Peak of nocturnal serum melatonin (pg/ml) Healthy n = 5 Chronic insomnia 82.5 n = % - 16% more than 5 yrs less than 5 yrs 72,1-38% 0 p = 0.01 Figure: Serum melatonin levels were significantly lower in patients with chronic primary insomnia (mean age 41.3 yrs) compared to healthy controls (mean age 27.2 yrs). The lowest values were found in chronic primary insomnia patients with a history of sleep disturbance lasting for longer than five years. Hajak G, Rodenbeck A, Staedt J, Bandelow B, Huether G, Ruther E. Nocturnal plasma melatonin levels in patients suffering from chronic primary insomnia. J Pineal Res 1995 Oct;19(3): Department of Psychiatry, University of Gottingen, Germany. 26

27 MLT and SLEEP Action: -reduction in core body temperature. -phase-shift of the endogenous circadian pacemaker. -direct action on somnogenic structures of the brain. Effects: -reduces time to fall asleep. -lengthens REM phase -increases quality of sleep(deep or slow wave sleep). -reduces number of night awakening. -even fractions of mlt(0,3 MG) enhance sleep. -No changes seen in total sleep time or sleep architecture -No changes seen in patients without insomnia

28 Significant beneficial effects of melatonin on sleep in elderly insomniacs Sleep parameters Sleep efficiency Melatonin Wake time after sleep onset Placebo 75 % 83 % Sleep latency Placebo Melatonin 33' 19' Placebo 73' Melatonin 49' Total sleep time was not affected onset 0 p < 0.0O1 p = (NS) p < 0.0O1 Figure: Sleep efficiency was significantly greater and wake time after sleep onset was significantly shorter in 12 elderly sunjects complaining from insomnia (aged 76 (SD 8) years) with melatonin therapy (2 mg/day of a controlled-release formulation during 3 weeks in a randomised,double-blind placebo-controlled cross-over study). Garfinkel D, Laudon M, Nof D, Zisapel N. Improvement of sleep quality in elderly people by controlled-release melatonin. Lancet 1995 Aug 26;346(8974):541-4 Day Care Unit, E Wolfson Medical Center, Holon, Israel. 28

29 GH & sleep

30 total time (minutes) GROWTH HORMONE Deficiency => SLEEP in GH deficient young adults Total sleep h nl 534 (+ 53 ) GH deficient Light sleep (stages 1 + 2) h nl 368 (+ 2 h) GH deficient (delta) (stages 3 + 4) (1 h 38) (- 24 ) (1 h 34) (- 22 ) Figure: growth hormone-deficient young adults have deep & REM sleep (study with 60 patients). (Aström C et Lindholm J, Neuroendocrinology, 1990; 51: 82-84) nl Deep sleep GH deficient REM sleep REM SLEEP corrected within the first 390 min sleep (the shortest total sleep time in controls) nl GH deficient

31 Figure: improvement of sleep efficiency after 6 months of growth hormone treatment (2 IU/M 2 /day) of growth hormone-deficient young adults. (Aström C et Lindholm J, Neuroendocrinology, 1990; 33: ) total time (minutes) GROWTH HORMONE THERAPY + SLEEP in growth deficient young adults TOTAL SLEEP GH (- 39 ) LIGHT SLEEP + GH (- 41 ) GH 0 DEEP SLEEP + GH (+ 15 ) REM SLEEP + GH (+ 27 )

32 Cortisol & insomnia

33 24-hr Cortisol rhythm & sleep night morning cortisol afternoon evening ACTH Figure :24 hours plasma cortisol and ACTH-levels in a normal subject in baseline conditions. These rhythms are poorly altered by sleep deprivation or a shift in bedtime hour. (Rev Prat (Paris), 1992, 42(5): 594) T. Hertoghe, ,

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35 Night serum cortisol µg/dl (nmol/l) Night serum cortisol Sleep 100 duration-sleep distruption healthy men w/ shorter sleep 76 (210) healthy men w/ longer sleep figure : healthy young men (aged yrs) w/ shorter total sleep time (7h57 ) have higher mean nocturnal serum cortisol than men w/ longer total sleep time (9h57 ). (Späth-Schwalbe E, J Clin Endocrinol Metab, 1992, 75: ) 56 (155) T. Hertoghe, , Brussels

36 Cushing syndrome deep sleep % of total sleep time Stage II 63.8% p < 0.05 p < 0.01 figure : in patients w/ Cushing s Syndrome delta-or deep sleep (as total sleep time) is by 59 % compared to controls, total sleep time is & stage II of superficial sleep is. 1994, 60: ) Cushing 74% +10% Delta-sleep (stages III + IV) 14% Cushing -59% 5.8% Cushing : total sleep time (-31 = 11%) REM, stage I (Friedman TC, Neuroendocrinology, T. Hertoghe, , Brussels

37 Testosterone & insomnia

38 SERUM TESTOSTERONE SLEEP REM REM REM REM testosterone figure : serum testosterone levels peak generally in proximity to the initiation of the REM periods in a young normal male. (Roffwarg HP et al, Psychosomatic Med, 1982, 44(1): 73-84) T. Hertoghe, , Brussels

39 DHEA & insomnia

40 DHEA sleep slee p time TOTAL SLEEP LIGHT SLEEP (stage ) (stage ) DEEP SLEEP REM SLEEP PLACEBO DHEA 500mg DHEA + 27 % EEG sigma activity first 2 h. GABA acid co-receptor complex % 19.3% of sleep of sleep figure : 500 mg oral DHEA duration of REM sleep & EEG activity in the sigma frequency range activity during REM sleep in the first 2 h. sleep period in 10 healthy young men (mean age of 24.9 yrs (21-30)). (Frien E et al, Am J Physiol. 1995; 268 (1 Rt 1) : )

41 Estrogens & insomnia

42 sleep parameters (minutes) ESTROGEN THERAPY IMPROVES SLEEP total sleep time placebo 19 sleep latency CE 12 placebo 7h6 CE 7h18 placebo REM CE Figure : mg daily conjugated estrogens the duration of REM-sleep and sleep latency in 16 hypogonadal women (aged yrs). (Schiff I, JAMA, 1979, 242: )

43 Progesterone & insomnia

44 Figure : 300mg to 10 healthy menopausal women their REM sleep, but their awake time without impairing cognitive functions during daytime. As possible mechanisms of progesterone a Gaba agonistic effect and the regulation of gene expression via the progesterone receptor are discussed. Progesterone might be useful in the treatment of sleep disturbances of postmenopausal women.(psychoneuroendocrinology Sep) PROGESTERONE REM, AWAKE TIME (SLEEP) AWAKE % of total sleep time % REM PG % TIME 13.7% PG 30.4% -26 0

45 Sleep: What happens with Aging?

46 Normal Sleep and Normal Aging: Sleep Efficiency The ability to get sufficient,continuous quality sleep may become more difficult as we age

47 Sleep among older adults --Many older adults don t get enough sleep: -Little deep sleep(3-4-sws) and more lighter sleep(stage 1,2 Variable).Decreased Sleep efficiency.fewer cycles. -Decreased REM Sleep. -Dozens of awakenings and arousal during the night. -Falling asleep takes longer. -Many older adults go to bed earlier at night and wake up earlier in the morning (Phase Advancement) -Older adults are more likely to nap during the day and have a decrease of psychomotor performance,sleepness

48 Normal Sleep and Normal Aging: Less Deep Sleep

49 Sleep Problems/Disorders Prevalent Among Older Persons SYMPTOMS OF SLEEP PROBLEMS BY AGE Symptoms: a few nights a week or more Insomnia 49% 46% 50% Snoring 41% 28% 22% Sleep Apnea 9% 6% 7% Restless Legs Syndrome (RLS) 15% 17% 21%

50 Sleep of the average 70-yr-old The average 70-year-old : sleeps only 6 hrs a night, may obtain 1 or 2 hrs more during daytime naps number of sleep disruptions incidence of chronic diseases or drugs that alter sleep=> poorer sleep the 2 most common geriatric sleep disorders = restless legs syndrome -obstructive sleep apnea syndrome Left untreated, sleep disorders => serious patient's health & morbidity & mortality. Barthlen GM. Sleep disorders. Obstructive sleep apnea syndrome, restless legs syndrome, andinsomnia in geriatric patients. Geriatrics Nov;57(11):34-9; quiz 40. Center for Sleep Medicine, Department of Neurology, Weill Cornell Medical College, New York, NY, USA

51 SLEEP DISORDERS AGING AGING RELATED DISEASES

52 Sleep 2009 Chronic Insomnia CVD DIABETES-OBESITY METABOLIC SYNDROME MOOD DISORDERS NEURODEGENERATIVE DISEASES INFLAMMAGING-IMMUNESEN.-CANCER UNSUCCESSFULL AGING

53 Sleep Disorders Aging related Hormones Deficiencies /Imbalances

54 Sleep Deprivation Six days of restricted sleep (4 hours per 24-hour period) caused changes to the sleep architecture similar to the changes seen in people suffering from depression. changes in several natural body rhythms of hormone secretion. Melatonin cortisol thyroid-stimulating hormone leptin Prolactin growth hormone. PCR-IL6-TNF

55 WHAT HAPPENS DURING AGING?

56 Alterations of Circadian Rhythmicity and Sleep in Aging: Endocrine Consequences Horm res Because sleep loss in young subjects results in endocrine disturbances which mimic those observed in aging, it is conceivable that the decrease in sleep quality which characterizes aging may contribute to age-related alterations in hormonal function and their metabolic consequences.

57 SLEEP DISORDERS-AGING HORMONAL GHRH TESTO GH- ANAB.H(IGF- 1-DHEAS TEST.)/CATAB H(CORT) IMBALANCES CRH CORT.CAT.VASO. PRL TNF-IL6 MELATONIN INSULIN - LEPTIN GHRL

58 Sleep disorders Hormones Deficiencies /Imbalances Unsuccessfull Aging Aging related Diseases

59 Nrem Sleep GH (35-50 yrs) JAMA Normal aging leads to sleep spindles and SWS,concurrent with a: reduced nocturnal GH release and of Th1 cytokines decrease of deep-restorative sleep (3-4 SWS) with increase of 1-2,no change on REM,on WAKE TIME and SLEEP TIME. truncal,abdominal obesity and lean body mass exercise response Declarative (Semantic)memory(hippocampal atrophy ) Immunological memories-immunesenescence

60 TH1 Sex hormones TH2 REM IL6 NONREM 3-4 SWS MLT GHRH-GH CRH ACTH CORTISOLO

61 Rem Sleep Cort.-IL6 ( >50 yrs)- JAMA Normal aging leads to an evening-night cortisol and day-night time IL6 with a Th2 -TH17cytokine shift ---sleep fragmentation,night awakenings REM WAKE TIME, SLEEP TIME, 1-2 NREM,3-4 NREM not significant. insulin-resistance,metab.sy,diabetes, CV risk,osteoporosis,sarcopenia,immunesenescence DAY-NIGHT TIME IL6,INFLAMMAGING,daytime fatiguedecreased performance, disability,morbility for age related diseases,mortality. Emotional Declarative(Episodic memory,amigdala dep),procedural memory

62 TH1 Sex hormones TH2 REM IL6 NONREM 3-4 SWS MLT GHRH-GH CRH ACTH CORTISOLO

63 SLEEP DISORDERS & AGING RELATED DISEASES -Cardio-Metabolic Risk Factors Obesity/body fat distribution Type 2 Diabetes Mellitus Hypertension Coronary Heart Diseas Cognitive disorders Immunesenescence-Autoimmune Diseases-Cancer Total and Cause-Specific Mortality

64 Chronic Sleep Loss, Behavioral or Sleep Disorder Related Weight gain, Insulin resistance, and Type 2 Diabetes.

65 Sleep and Diabetes Sleep problems: risk factors for Diabetes Sleep problems worsen Diabetes Sleep deprivation worsens insulin resistance and glucose intolerance Sleep apnea does the same Control of sleep problems improves DM CPAP improves Diabetes control

66 Acute Sleep Loss Causes Insulin Resistance 4 hours of acute sleep loss for 6 days: 40% reduction in rate of glucose clearance 30% reduction in insulin effectiveness Decreased thyroid hormone Increased evening cortisol Increased sympathetic nervous system activity (CATECOLAMIN) (similar changes to that seen in obesity & aging) Spiegel K, Leproult R, Van Cauter E. Lancet 354:1435-9, 1999

67 Chronically Short Sleepers Have Insulin Resistance Chronically short sleepers (306 vs 486 min/nt) Secreted 65% more insulin Insulin sensitivity 40% less than normal Significantly decreased reaction times Lower scores on the Global Affect scale Colecchia EF, Spiegel K, Kim R, et al. Sleep 23:A253, 2000

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69 Relative Risk Sleep Duration and Risk of Diabetes The Massachusetts Male Aging Study (n=1,139) ( ) ( ) <= >8 Hours of Sleep Yaggi HK et al. Diabetes Care 2006; 29:657-61

70 Sleep Deprivation & Diabetes: Potential Mechanisms Elevation of evening cortisol levels predisposing to insulin resistance. Increase in sympathetic tone, inhibiting pancreatic function and leading to increased glucose intolerance. Weight gain,reduction in leptin,increase of ghrelin. Reduction of testosterone levels.

71 Type 2 Diabetes and OSA -80% of type 2 diabetics are overweight and in particular have central obesity Central obesity increases the risk of OSA 12% of type 2 diabetics had moderate to severe OSA - 70% of moderately obese diabetics who snored or were sleepy had OSA

72 Cardio-Metabolic Risk Factors: Obesity

73 Obesity and Sleep Deprivation Direct link between avoiding sleep and obesity. Risk of obesity rises with sleep deprivation: Less than 4 hours : 73% risk Five hours Six hours : 50% risk : 23% risk

74 Obesity Epidemic and Sleep Duration BMI in US adults 28,0 27,0 26,0 25,0 24,0 23,0 22,0 21,0 26,9 25,2 23, Sleep duration in US adults 10,0 9,0 8,0 7,0 6,0 5,0 4,0 3,0 2,0 1,0 0,0 9,0 7,5 6,

75 Chronically Short Sleepers Have Increased BMI Study of 1024 subjects with chronic sleep restriction showed an association with reduced leptin, increased ghrelin and elevated BMI. Taheri S, et al, Sleep 27: A146-7, 2004.

76 Sleep Deprivation Causes Obesity growth hormone lean muscle mass fat mass testosterone lean muscle mass fat mass leptin and leptin resistance ghrelin insulin resistance evening cortisol sympathetic activity: --- fatigue: exercise --- eating for energy

77 Metabolic Sydrome Early risk factor: cardiovascular disease Affects: 50 million Americans High waist: men >40 women >35 -OBESITY High triglycerides: >150 mg/dl Low HDL: men <40mg women <50mg High blood pressure: >130/85 High fasting glucose: >100 insulin levels and insulin resistance uric acid Add: Sleep deprivation or Sleep Apnea

78 Similarities between Sleep Deprivation, Obesity and Aging Sleep quality and quantity Growth hormone, testosterone Evening cortisol, catecholamines insulin resistance glucose tolerance Incidence of Diabetes and Cardiovascular Diseases

79 Chronic Sleep Loss, Behavioral or Sleep Disorder Related CVD

80 Cardio-Metabolic Risk Factors: Hypertension

81 Relative Risk Relative Risk Sleep duration and prevalent Hypertension The Whitehall II Study 2,0 1,5 1, ( ) 0,92 Women, n=1, P = ,5 0,0 2,0 1,5 1, Men, n=4, ,86 0,92 0,5 0,0 <= >=9 Hours sleep Cappuccio FP et al. Hypertension 2007:50:

82 Sleep Deprivation & Hypertension: Potential Mechanisms Increased BP load resulting from prolongation of higher BP whilst awake Truncation of the BP dip during sleep Prolonged activation of sympathetic nervous system Increased renal sodium retention Decreased nocturnal peak of MLT Increased nadir nocturnal level of Cortisol Gender-specific effects? Confounding?

83 MLT and Blood Pressure MLT reduces night blood pressure in patients with nocturnal hypertension and is a potential antihypertensive treatment. (Am J.Med 2006-J.Pin.Res.2007). The administration of the hormone declines blood pressure to normal range. It has been observed that MLT, even in a dose 1 mg, reduced blood pressure and decreased catecholamine level after 90 min in human subjects.

84 MLT and Blood Pressure ---MLT may reduce blood pressure via the following mechanisms: 1) by a direct effect on the hypothalamus. 2) as an antioxidant which lowers blood pressure. 3) by decreasing the level of catecholamines. 4) by relaxing the smooth muscle in the aorta wall.(no release) Paulis L.Physiol. Res. 56: , 2007

85 Coronary Heart Disease

86 Relative Risk Relative Risk Coronary Heart Disease by hours of sleep The MONICA Study 3,0 2, ( ) Women, n=3,388 2,0 1,5 1,0 1,34 1, ,5 0,0 2,0 Men, n=3,508 1,5 1, ,05 1, ,07 0,5 0,0 <= >=9 Hours sleep Meisinger C et al. Sleep 2007; 30:

87 Summary Both short and long sleep duration may be associated with more detrimental effects on cardiovascular health in women than men. The biological mechanisms underlying these associations are unclear. High blood pressure may represent one mechanism linking short sleep duration with increased risk of CHD, at least in women

88 HORMONES LIPID-GLUCO METABOLISM HOMOCYSTEINE BLOOD PRESSURE OXIDATIVE STRESS CV PROTECTION ENDOTHELIAL FUNCTION INFLAMMATION

89 MLT and CAD Patients with coronary disease have a low Mlt production rate, with greater decreases in those with higher risk of cardiac infarction and/or death. Incidence of sudden cardiac death is high in the morning hours. It has been shown that Mlt levels are significantly low at these times. Low urinary 6-sulphatoxymelatonin levels in patients with Coronary Artery Disease(J.Pin. Res.2000).

90 TOTAL amt6s EXCRETION RATE and CAD g/24h Healthy *** *** CAD * * p <.05 *** p <.001 CAD with higher risk of infarction and/or death

91 Ask all patients with hypertension, heart disease or diabetes Do you snore? Do you wake up refreshed? Has anyone told you that you stop breathing in your sleep?

92 QUALITY SLEEP SUCCESSFULL AGING

93 Sleep and Aging NSF 2003 Sleep in America poll The first NSF poll to look at the sleep habits of older Americans -- those between the ages of 55 and and the association between their sleep behavior, their medical and physical conditions, their outlook and their lifestyles.

94 Sleep and Aging NSF poll found that the better the health of older adults, the more likely they are to sleep well The greater the number of diagnosed medical conditions, the more likely they are to report sleep problems. Positive moods and outlooks as well as having more active and "engaged" lifestyles (having someone to speak with about a problem, exercise, volunteer activity, etc.) are associated with sleeping 7 9 hours and fewer sleep complaints.

95 Sleep and Aging Rather than a consequence of aging, poor sleep among older Americans appears to be an indicator of health status.

96 Sleeping well, aging well: a descriptive and cross-sectional study of sleep in "successful agers" 75 and older. Am J Geriatr Psychiatry Jan;16(1): Objective:To examine diary-based, laboratory-based, and actigraphic measures of sleep in a group of healthy older women and men (> or =75 years of age) without sleep/wake complaints and to describe sleep characteristics which may be correlates of health-related quality of life in old age. CONCLUSIONS: Sleep quality and daytime alertness in late life may be more important aspects of successful aging than previously appreciated. Good sleep may be a marker of good functioning across a variety of domains in old age. Our observations suggest the need to study interventions which protect sleep quality in older adults to determine if doing so fosters continued successful aging.

97 Protecting sleep, promoting health in later life: a randomized clinical trial. Psychosom Med Feb;72(2): CONCLUSIONS: Although we cannot exclude a positive effect of education in healthy nutrition, for healthy elderly >75 years of age without sleep complaints, reducing sleep time may be detrimental, whereas allowing more time to sleep (about 7.5 hours nightly) is associated with better maintenance of physical health-related quality of life and stability of medical illness burden over 30 months.

98 Total and Cause-Specific Mortality

99 Chronic Sleep Loss, Behavioral or Sleep Disorder Related MORTALITY

100 Centenarians: Satisfying sleep Long-living persons: -Regular & satisfying sleep (6 8 h) Dan Georgekas, The Methusaleh Factors, Ed. Academy of Chicago Publishers 1995,

101 Centenarians: A well-balanced sleep-wake cycle 52 Centenarians: 36 women 16 men The majority got up early & liked to work outdoors. Humphrey GM, Young TH. On Centenarians ( 1899)

102 ALTERED BIOLOGICAL RHYTHMS AGING ARD

103 What s the Ideal Sleeping Time?

104 7 hrs = Optimal Sleep duration => longevity 104,010 subjects (43,852 men & 60,158 women), aged 40 to 79 years Prospective study (JACC Study = Japan Collaborative Cohort Study on Evaluation of Cancer Risk ) Mean follow-up 9.9 yrs Sleep duration of shorter or longer than 7 hrs was assoc. w/ a sign. risk of allcause mortality Sleep duration at night of 7 hrs was found to show the lowest mortality risk Tamakoshi A, Ohno Y; JACC Study Group. Self-reported sleep duration as a predictor of all-cause mortality: results from the JACC study, Japan. Sleep Feb 1;27(1):51-4. Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya , Japan. tamaa@med.nagoya-u.ac.jp

105 All-Cause mortality by hours of sleep The Whitehall II Study Phase 1 ( ) n=9,781 Phase 3 ( ) n=7,729 4 Hazard Ratio (95% CI) Age-adjusted Fully adjusted 4 Hazard Ratio (95% CI) Age-adjusted Fully adjusted < 5h (56 deaths) 6h (160 deaths) 7h (256 deaths) 8h (87 deaths) > 9h (7 deaths) 0 < 5h (29 deaths) 6h (61 deaths) 7h (112 deaths) 8h (74 deaths) > 9h (16 deaths) Ferrie JE et al. Sleep 2007; 30:

106 Summary Either a decrease in sleep duration from a regular 6, 7 or 8h per night or an increase from a regular 7 or 8h per night predict all-cause mortality A decrease in sleep duration affects all-cause mortality via increases in cardiovascular deaths An increase in sleep duration affects overall mortality via an increase in non-cardiovascular deaths Sleep changes over time may represent more reliable measures to assess the impact of sleep on health

107 Sleep duration and all-cause mortality: a systematic review and metaanalysis of prospective studies. Cappuccio FP, D'Elia L, Strazzullo P, Miller MA.-SLEEP-2010 University of Warwick, Warwick Medical School, Clinical Sciences Research Institute, Coventry, UK. CONCLUSION: Both short and long duration of sleep are significant predictors of death in prospective population studies.

108 Sleep is the golden chain that ties health and our bodies together. Thomas Dekker, English Dramatist ( )

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