Sleep,Hormones,Immunity,Longevity
andSuccessful Aging
ASCANIO POLIMENI M.D. NEUROENDOCRINOLOGISTCONDIRECTOR of “REGENERA RESEARCH GROUP”
Health-Disease
We are
What We:
Eat Feel
Think
BreathDrink
We are also..
How We:
SLEEPSLEEP is an essential a component as Good
Nutrition,Water,Air and Exercise toOptimal Health, to our Mental-Physical Performances
and to Quality of Life
Awake
Sta
ges
The Sleep Cycle in Adults
RE
M
RE
M
RE
M
RE
M
RE
M
1
2
3
4
0 1 2 3 4 5 6 7 8
Hours in Sleep
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
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.
Relationship between sleep,
circadian rhythm,
and the neuroendocrine,
autonomic nervous
and immune systems.
MLT
GHRH-GH
PRL
TH1
CRH
ACTH
CORTISOLO
TH2
NONREM
SWS
REM
Sleep influences
circadian alternance between TH1-TH2
immune system branches
Putative pathways of immune
system involvement in sleep.
In general, pro-inflammatory cytokines induce sleep,
whereas anti-inflammatory cytokines inhibit sleep.
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.
Awake
Sta
ges
The Sleep Cycle in Adults
RE
M
RE
M
RE
M
RE
M
RE
M
1
2
3
4
0 1 2 3 4 5 6 7 8
Hours in Sleep
Sleep Hormonesdifferent 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)-
(x ± SEM)pg/ml
2 4 8 12 16 20 220
10
20
30
40
50
60
70
0 24 L/D
PLASMA MELATONIN CIRCADIAN RHYTHM
day night
*** p < .001%
of th
e tota
l 24
h
0
10
20
30
40
50
60
70
80
* *
*
DAY / NIGHT aMT6s URINARY EXCRETION
% Rhythm
MESOR M
(x ± SEM) (x ± SEM)
AMPLITUDE A ACROPHASE
(°)
(95% c.l.)
hours
YOUNG CONTR.
(n=15)
p
0.0002 55.54 21.12 ± 3.23 17.16 ± 2.91 - 22° 28'
(-04° 05' to - 47° 03')
01:30
(00:16 to 03:08)
Ø §Population
mean
cosinor
summary
Pineal gland
Cortisol
12 0 12h
12 0 12h
Sleep / Wakefulness
12 0 12 h
Temperature
Melatonin12 0 12h
Light / Dark
SCN
Circadian rhythms
MELATONIN RHYTHM AS ENDOGENOUS SYNCHRONIZER FOR OTHER
RHYTHMS
CIRCADIAN RHYTHM OF
MLT
CORTISOL
GH
INSULIN-ADIPONECTIN
LEPTIN-GHRELIN
FSH-LH
T4 T3
MLT
GHRH-GH
CRH
ACTH
CORTISOLO
SS
NONREM
SWS
REM
-------------
Hypothalamic NPY
LEPTIN FAT MASS
INTERACTION LEPTIN - NPY
food intake
BAT activity
insulin secretion
-
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;101:10434-10439
©2004 by National Academy of Sciences
TEST??
Hormones SleepA number of hormones are known to modify sleep and sleep
propensity
Sleep inducing 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
Sleep reducing hormones
ACTH-CRH
Cortisol-Catecholamines
Pregnenolone
Somatostatin
Thyreotropin releasing
hormone(t3-t4)
Endorphine
Prostaglandine E
Th2-cytokines
Melatonin&
Sleep
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
0
30
60
90
120
82.5
p = 0.01
116.8Peak of
nocturnal
serum
melatonin
(pg/ml)
98.26
72,1
Chronic
insomnia
- 29 %
more
than 5 yrs
Healthy
Chronic insomnia
less
than 5 yrs
- 16%- 38%
n = 10n = 5
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):116-22 Department of Psychiatry, University of Gottingen, Germany.
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.
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
0
30
60
90
33'
p < 0.0O1
83 %
Sleep
parameters
73'
Melatonin
Placebo
Melatonin
Melatonin
75 %
p = 0.088 (NS)
Sleep efficiency Wake time
after sleep onset
Sleep latency
19'
49'
Placebo
Placebo
p < 0.0O1
Total
sleep time
was not
affected
onset
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.
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).
GH& sleep
GROWTH HORMONE Deficiency => SLEEP in GH deficient young adults
Figure: growth hormone-deficient young adults have deep & REM sleep (study with 60 patients). (Aström C et
Lindholm J, Neuroendocrinology, 1990; 51: 82-84)
0
100
200
300
400
500
600
8 h
4 h
(+ 53 ‘)
(+ 2 h)
(- 24 ‘) (- 22’)(1 h 38) (1 h 34)
nl GH deficient
REM SLEEP corrected within the first 390 min sleep (the shortest total sleep time in controls)
(stages 1 + 2)
(delta)(stages 3 + 4)
479
534
246
368
98 7494 72
Light sleep
Deep sleep
REM sleep
Total sleep
nlnlnlGH
deficientGH
deficient
GH deficient
total time (minutes)
GROWTH HORMONE THERAPY + SLEEP in growth deficient young adults
total time (mi-nutes)
Figure: improvement of sleep efficiency after 6 months of growth hormone treatment (2 IU/M2/day) of growth hormone-deficient young adults. (Aström C et Lindholm J, Neuroendocrinology, 1990; 33: 495-500)
0
100
200
300
400
500
600
TOTAL SLEEP
0
0
0
(- 39’)
(- 41’)
(+ 15’ )
(+ 27’)
+ GH
+ GH
REM SLEEPLIGHT
SLEEP
DEEP SLEEP558
518
350
309
64 79111 138
+ GH
+ GH
+ GH
Cortisol&
insomnia
24-hr Cortisol rhythm & sleep
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, 02-2000,
Brussels
ACTH
cortisolnight
morningafternoon
evening
0
20
40
60
80
100
Night serum cortisol Sleep
duration-Sleep distruption
Night
serum
cortisol
µg/dl
figure : healthy young men (aged 20-34 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: 1431-1435)
© T. Hertoghe, 02-2000, Brussels
healthy men w/
shorter sleep
56
(210)
76
(nmol/l)
healthy men w/
longer sleep
(155)
0
20
40
60
80
100
Cushing syndrome deep sleep
% of
total
sleep
time
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 . (Friedman TC, Neuroendocrinology, 1994, 60: 626-634)
Cushing
© T. Hertoghe, 02-2000, Brussels
Stage II Delta-sleep
(stages III +
IV)
Cushing :
• total sleep time (-31’= 11%)
• REM, stage I
63.8% 74%
14%5.8%
p < 0.05 p < 0.01
Cushing
-59%
+10%
Testosterone&
insomnia
SERUM TESTOSTERONE SLEEP
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, 02-2000, Brussels
REM REMREM REM
testosterone
DHEA &
insomnia
DHEA sleepPLACEBO
DHEATOTAL
SLEEP LIGHT
SLEEP
DEEP
SLEEP
500mg DHEA
+ 27 %EEG sigma activity first 2 h. GABA acid co-receptor complex
slee
p
time
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) : 107-13)
15.7% 19.3%of sleep of sleep
409.1423.2
261.1(stage
2 230.6)
258.7(stage
2 228.3)
67.9 68.4 69.6 88.4
REM
SLEEP
Estrogens&
insomnia
0
100
200
300
400
500
ESTROGEN THERAPY IMPROVES SLEEP
sleep
para-
meters
(minutes)
Figure : 0.625 mg daily conjugated estrogens the duration of REM-sleep and sleep latency in 16 hypogonadal women (aged 31-65 yrs).
(Schiff I, JAMA, 1979, 242: 2405-2407)
total sleep time
placebo
19’
CE
12’
REMsleep
latency
CE
CE
+25’
placebo
7h18’
7h6’
70.4’ 95.4’
placebo
Progesterone&
insomnia
0
10
20
30
40
50
PROGESTERONE REM, AWAKE TIME (SLEEP)
% of
total
sleep
time
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. 2008 Sep)
PGREM
13.5%13.7%
18%
+15’
30.4%
AWAKE
TIME
-26’
PG
Sleep:
What
happens
with Aging ?
Normal Sleep and Normal Aging:Sleep Efficiency
The ability to get
sufficient,continuous quality sleep may
become more
difficult as we age
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
Normal Sleep and Normal Aging:Less Deep Sleep
Sleep Problems/DisordersPrevalent Among Older Persons
SYMPTOMS OF SLEEP PROBLEMS BY AGE
Symptoms: a few nights
a week or more 55-64 65-74 75-84
Insomnia 49% 46% 50%
Snoring 41% 28% 22%
Sleep Apnea 9% 6% 7%
Restless Legs Syndrome (RLS) 15% 17% 21%
Sleep of the average 70-yr-oldThe 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 =
-obstructive sleep apnea syndrome
restless legs 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. 2002 Nov;57(11):34-9; quiz
40. Center for Sleep Medicine, Department of Neurology, Weill Cornell Medical College, New York, NY, USA
SLEEP
DISORDERS
AGING
AGING RELATED DISEASES
Sleep 2009
Chronic Insomnia
CVD
DIABETES-OBESITY
METABOLIC SYNDROME
MOOD DISORDERS
NEURODEGENERATIVE DISEASES
INFLAMMAGING-IMMUNESEN.-CANCER
UNSUCCESSFULL AGING
Sleep
Disorders
Aging related
Hormones
Deficiencies
/Imbalances
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
WHAT HAPPENS
DURING AGING?
Alterations of Circadian
Rhythmicity and Sleep in Aging:
Endocrine Consequences
Horm res-1998-
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.
SLEEP DISORDERS-AGING
HORMONAL IMBALANCES
GH-
GHRH TESTO
ANAB.H(IGF-
1-DHEAS
TEST.)/CATAB
H(CORT)
CRH
CORT.CAT.VASO.
PRL
MELATONIN
TNF-IL6
INSULIN - LEPTIN GHRL
Sleep
disorders
Hormones
Deficiencies
/Imbalances
Unsuccessfull Aging
Aging related
Diseases
Nrem Sleep GH (35-50 yrs) JAMA -2000-
---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
MLT
GHRH-GH
TH1
CRH
ACTH
CORTISOLO
TH2
NONREM
3-4 SWS
REM IL6
Sex
hormones
Rem Sleep Cort.-IL6 ( >50 yrs)-JAMA 2000-
- 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 fatigue-
decreased performance, disability,morbility for age related
diseases,mortality.
Emotional Declarative(Episodic memory,amigdala
dep),Procedural memory
MLT
GHRH-GH
TH1
CRH
ACTH
CORTISOLO
TH2
NONREM
3-4 SWS
REM IL6
Sex
hormones
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
Chronic Sleep Loss,
Behavioral or Sleep
Disorder Related
Weight gain,
Insulin resistance,
and Type 2
Diabetes.
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
Acute Sleep Loss Causes InsulinResistance
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
Chronically Short Sleepers HaveInsulin 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
Sleep Duration and Risk of DiabetesThe Massachusetts Male Aging Study (n=1,139)
0
1
2
3
4
5
6
<=5 6 7 8 >8
Hours of Sleep
Re
lati
ve
Ris
k
Yaggi HK et al. Diabetes Care 2006; 29:657-61
1.95 (0.95-4.01)
3.12 (1.53-6.37)
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.
Sleep Deprivation & Diabetes:Potential Mechanisms
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
Cardio-Metabolic Risk Factors:
Obesity
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 : 50% risk
Six hours : 23% risk
Obesity Epidemic and Sleep Duration
7,56,8
9,0
0,0
1,0
2,0
3,0
4,0
5,0
6,0
7,0
8,0
9,0
10,0
1910 1975 2005
Sleep duration in US adults
25,2
26,9
23,0
21,0
22,0
23,0
24,0
25,0
26,0
27,0
28,0
1910 1975 2005
BMI in US adults
Chronically Short Sleepers HaveIncreased 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.
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”
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
Similarities between SleepDeprivation, Obesity and Aging
↓ Sleep quality and quantity
↓ Growth hormone, testosterone
↑ Evening cortisol, catecholamines
↑ insulin resistance
↓ glucose tolerance
↑ Incidence of Diabetes and Cardiovascular
Diseases
Chronic Sleep
Loss, Behavioral
or Sleep Disorder
Related
CVD
Cardio-Metabolic Risk Factors:
Hypertension
Cappuccio FP et al. Hypertension 2007:50:694-701
Sleep duration and prevalent Hypertension The
Whitehall II Study
0.70
1.00,92
0.74
0,0
0,5
1,0
1,5
2,0
Re
lati
ve
Ris
k
0,86 0,921.01.12
0.88
0,0
0,5
1,0
1,5
2,0
<=5 6 7 8 >=9
Re
lati
ve
Ris
k
Hours sleep
Women, n=1,567
Men, n=4,199
1.72 (1.07-2.75)
P = 0.037
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?
Sleep Deprivation & Hypertension:Potential Mechanisms
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.’’
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: 671-684, 2007
Coronary Heart Disease
Coronary Heart Disease by hours of sleepThe MONICA Study
1.401,341,05 1.0
0,0
0,5
1,0
1,5
2,0
2,5
3,0
Re
lati
ve
Ris
k
1,051,22
1,071.01.13
0,0
0,5
1,0
1,5
2,0
<=5 6 7 8 >=9
Re
lati
ve
Ris
k
Hours sleep
Women, n=3,388
Men, n=3,508
2.98 (1.48-6.03)
Meisinger C et al. Sleep 2007; 30:1121-27
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
CV PROTECTION
ENDOTHELIAL
FUNCTION
LIPID-GLUCO
METABOLISM
INFLAMMATION
HOMOCYSTEINE
HORMONES
BLOOD
PRESSURE
OXIDATIVE
STRESS
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 withCoronary Artery Disease(J.Pin. Res.2000).
02468
10121416
18
******
*
g/24h
TOTAL aMT6s EXCRETION RATE and CAD
* p < .05
*** p < .001
Healthy CAD with higher risk
of infarction and/or death
CAD
Ask all patients withhypertension, heart disease or
diabetes…
Do you snore?
Do you wake up refreshed?
Has anyone told you that you stop
breathing in your sleep?
QUALITY
SLEEP
SUCCESSFULL
AGING
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 84 -- and the association between their sleep
behavior, their medical and physical conditions,
their outlook and their lifestyles.
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.
Sleep and Aging
Rather than a consequence of
aging, poor sleep among older
Americans appears to be an
indicator of health status.
Sleeping well, aging well: a descriptive and cross-sectional study of sleep in "successful agers" 75 and older.
Am J Geriatr Psychiatry. 2008 Jan;16(1):74-82.
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.
Protecting sleep, promoting health in later life: a randomized clinical trial.
Psychosom Med. 2010 Feb;72(2):178-86
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.
Total and
Cause-Specific Mortality
Chronic Sleep Loss,
Behavioral or Sleep
Disorder Related
MORTALITY
Centenarians:
Satisfying sleep
Long-living
persons:
-Regular &
satisfying sleep
(6 – 8 h)
Dan Georgekas, The Methusaleh Factors, Ed. Academy of Chicago Publishers 1995, 153-172
The majority got up early
&
liked to work outdoors.
52 Centenarians: 36 women 16 men
Humphrey GM, Young TH. On Centenarians ( 1899)
Centenarians:
A well-balanced sleep-wake cycle
ALTERED
BIOLOGICAL
RHYTHMS
AGING
ARD
What’s the
Ideal
Sleeping
Time?
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
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. 2004 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 466-8550, Japan. [email protected]
Sleep duration of
shorter or longer than
7 hrs was assoc. w/ a
sign. risk of all-
cause mortality
Sleep duration at
night of 7 hrs was
found to show the
lowest mortality risk
All-Cause mortality by hours of sleepThe Whitehall II Study
0
1
2
3
4
< 5h
(56 deaths)7h
(256 deaths)
8h
(87 deaths)
Hazard Ratio (95% CI)
Age-adjusted
Fully adjusted
6h
(160 deaths)
> 9h
(7 deaths)
Phase 1 (1985-88) n=9,781
0
1
2
3
4
< 5h
(29 deaths)7h
(112 deaths)
8h
(74 deaths)
Hazard Ratio (95% CI)
Age-adjusted
Fully adjusted
6h
(61 deaths)
> 9h
(16 deaths)
Phase 3 (1991-93) n=7,729
Ferrie JE et al. Sleep 2007; 30:1659-66
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
Sleep duration and all-cause mortality: a systematic review and meta-analysis 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.
Sleep is the golden chain that ties
health and our bodies together.Thomas Dekker, English Dramatist (1572 - 1632)