dissertation defense interactions between exercise, aging and ethanol
DESCRIPTION
Dissertation presentation for Steven B. HammerTRANSCRIPT
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Steven B. HammerPh. D. Candidate
Department of Biomedical SciencesKent State University
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Circadian Rhythms
Examples
•Core body temperature
•Peak muscle performance
•Hormone levels
•Digestion
•Child Birth
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Circadian System Input
Photic Light flash
Non-photic Drugs Sound Exercise
Processing SCN
Cyclic transcription/translation feedback loops
Output Hypothalamus Thalamus Effector Organs
IGL
MRN
RHT
GHT
Light
DRN
5-HT 5-HT
GlutamatePACAP
NPYGABA
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Evolution of Phase Shifting
Adjust for seasonal changesHibernation, short and long days
Man made “Daylight Savings Time”Farmers
TravelEast or West bound?
Workshifts
Basic leveldaily changes
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Phase Response Curve
ZT 6.0Peak Phase advance (non-photic stimulus)
ZT 18.5 Phase advance from light pulse
Dead
Zone
ZT 14Phase delay from light pulse
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Hormone/Receptor Increase Decrease No Change
Dopamine - + -
Dopamine Receptor 1 + - +
Dopamine Receptor 2 - + -
MAO A - + +
MAO B + - -
Noradrenaline - + -
Serotonin - + +
GABA - + -
Muscarinic Receptor - + -
Choline Acyltransferase
- + -
Beta Endorphin - + -
Alpha MSH - + -
ACTH - + -
Beta Lipotropin - + -
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Hormone/Receptor Increase Decrease No Change
FSH + - -
LH + - -
Inhibin - + -
Testosterone - + +
LHrh - + -
Aldosterone - + -
GH - + -
TSH - + +
Thyroxin - - +
Tri-iodothyronine - - +
ADH + - +
Oxytocin - + -
Prolactin + + +
Melatonin - + -
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Alcohol Consumption
Baby BoomersRetirementEtOH consumption
Shift WorkDrinking to unwind/relax after night shift
Delay onset of activity
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Death
Addiction
Late For Work
Decreased Ability To Perform ADL’s
Increase Stress
Increased Addiction
Increase in Family, Social, and Family
Problems
Increased Cost On Society
Increase Morbidity And Mortality Rates
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Females MalesDrinking Category*
Disease I II III I II IIIMalignant neoplasms Mouth and oropharynx cancers 1.45 1.85 5.39 1.45 1.85 5.39 Esophagus cancer 1.80 2.38 4.36 1.80 2.38 4.36 Liver cancer 1.45 3.03 3.60 1.45 3.03 3.60 Breast cancer 1.14 1.41 1.59 Under 45 years of age 1.15 1.41 1.46 45 years and over 1.14 1.38 1.62 Other neoplasms 1.10 1.30 1.70 1.10 1.30 1.70 Diabetes mellitus 0.92 0.87 1.13 1.00 0.57 0.73Neuropsychiatric conditions Epilepsy 1.34 7.22 7.52 1.23 7.52 6.83Cardiovascular diseases (CVD) Hypertensive disease 1.40 2.00 2.00 1.40 2.00 4.10 Coronary heart disease 0.82 0.83 1.12 0.82 0.83 1.00 Cerebrovascular disease Ischemic stroke 0.52 0.64 1.06 0.94 1.33 1.65 Hemorrhagic stroke 0.59 0.65 7.98 1.27 2.19 2.38 Other CVD causes 1.50 2.20 2.20 1.50 2.20 2.20Digestive diseases Cirrhosis of the liver 1.26 9.54 9.54 1.26 9.54 9.54
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Effects of Exercise
Increased fitness results in Increased blood flow Lean muscle mass Enzyme system/Biochemical pathways Substrate utilization
Decrease Depression by increasing NPY Serotonin Dopamine Norepinephrine
Improved Sleep Longer life? Quality of Life Increase adaptive ability to time changes Increased ability to deal with shift work
Bupropion
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Interactions of Aging, EtOH and Exercise
Biochemical changes seen with agingSimilar to those seen with depression and EtOH abuse
Exercise decreases morbidity and mortality ratesAttenuates many of the biochemical changes associated
with agingReplacement of one addiction for another
“Ended my streak of consecutive days running on Sunday at 178. It was bittersweet but for the best. As my mileage got higher I really felt my body needed it. And a friend convinced me that the whole "On the seventh day God rested" thing may be in the Bible for a reason. :) Good luck to all of you as you try to balance determination and perseverance with what's best for you and your body”.(Endurance Planet web site, Unknown Author, June 30 2009 )
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Specific Aims
AIM 1: To determine if exercise, either forced or voluntary, affects photic and or non-photic phase shifting in the Syrian hamster
AIM 2: To determine if aging, combined with exercise, affect non-photic phase shifting in the Syrian hamster
AIM 3: To determine if exercise and aging affect activity onset when measured by infrared versus wheel sensors
AIM 4: To determine if exercise affects the consumption of ethanol, and if there are interaction between aging, exercise, and ethanol consumption
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General Methods
Syrian hamsters (Mesocricetus auratus)Individually housedLights (LD 14:10, DD and LL)1 to 26 months of agePassive IR sensors mounted above each cageMagnetic wheel sensors to measure wheel
running5mg (8-OH-DPAT)/kg (body mass)/ml (DMSO) EtOH 20%
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Experiment Series OneTreadmill Running
(1A) Forced running Young
Runners (5 months, n=6) Controls (5 months, n=6)
Old Runners (19 months, n=7) Controls (19 months, n=7)
1 hour per day 4 weeks (LD, 14:10) 30 minute light pulse
(ZT 18.5)
Treadmill Running (1B)
Forced running Young
Runners (5 months, n=5) Controls (5 months, n=5)
Old Runners (19 months, n=9) Controls (19 months, n=10)
1 hour per day 13 weeks (LD, 14:10) 8-OH-DPAT (CT 6.0)
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Experiment Series One
Wheel Running(1C)
Voluntary runners Young
Runners (6 months, n=6) Controls (6 months, n=6)
Old Runners (24 months, n=6) Controls (24 months, n=6)
13 weeks (LD, 14:10) Continuous running 8-OH-DPAT (CT 6.0)
Wheel Running(1D)
Voluntary runners Three age groups
6 months (n=6) 9 months (n=6) 14 months (n=6)
28 weeks (DD) Continuous running 1 injection per month for 4
months; 8-OH-DAPT at (CT 6.0)
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Photic Phase Shift Comparison After Four Weeks of Forced Treadmill Running
Phot
ic Ph
ase A
dvan
ce (h
ours
)
Young Old1.6
1.7
1.8
1.9
2.0
2.1
2.2
2.3
2.4
2.5
Young Old
Non-running Running
*
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Fig. 2: Non-P hotic phas e s hift after 13 week s of forc ed treadm ill running (1 hour/day ); 8-O H-DP A T (5m g/k g) and DM S O (vehic le)
DP A T DM S O M e a n M e a n ± S E
No
n-P
ho
tic P
hase A
dvan
ce (
ho
urs
)
Young Old0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
Young Old0.0
0.2
0.4
0.6
0.8
1.0
1.2
1.4
1.6
1.8
2.0
a
aa
a
b
bb b
Control Running
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Treadmill Running
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The Effects of 13 Weeks of Wheel Running on The Non-photic Phase Shifting of Young and Old Syrian hamsters
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Effects of Aging on Non-photic Shifting and Running Distance
Revolutions per Day Non-Photic Phase Shift
40 45 49 52 55 57 66 787461 83 88 40 45 49 52 55 57 66 787461 83 88
Weeks of Age
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Experiment TwoActivity Onsets
Wheel Running(3B)
Voluntary runners Young (3-4 months,
n=18) 60 days Half of the animals have
access to 20% EtOH half do not
Wheel Running(1C)
Voluntary runners Young
Runners (6 months, n=6) Controls (6 months, n=6)
Old Runners (24 months, n=6) Controls (24 months, n=6)
13 weeks (LD, 14:10) Continuous running 8-OH-DPAT (CT 6.0)
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Effects of Running and Age on Non-photic shifting
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Onsets of Activity between IR and WS grouped by EtOH and Water
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Experiment Series Three
Access to 20% EtOH and Water (3A)
LD (14:10) Young (2 months, n=18)
Runners (n=9) (Phase 2) Controls (n=9)
Old (24 months, n=15) Runners (n=8) (Phase 2) Controls (n=7)
Three Phases Phase 1 (10 days)
all wheels locked Phase 2 (30 days)
half wheels locked half unlocked
Phase 3 (20 days) all wheels locked
Voluntary Running (3B)
LD (14:10) Young (3-4 months, n=18) 60 days EtOH drinkers (n=9) Controls (water) (n=9)
(3C) LL (Constant Light) Same animals as experiment
(3B)
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1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61
Da ys
-20
0
20
40
60
80
100
120
140
160
180
Wat
er C
on
sum
pti
on
(g
/kg
/day
) Control Tre a tm e nt
P ha se I P ha se II P ha se III
Treatmen t C o n tro l
40
60
80
100
120
140
160
180
200
**
#
#
Ph ase I Ph ase I I Ph ase I I I Ph ase I Ph ase I I Ph ase I I I
* #
Da ys
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61
0
2
4
6
8
10
12
14
16
EtO
H C
on
sum
pti
on
(g
/kg
/day
)
Treatm ent
Control
Treatmen t C o n tro l
11.011.512.012.513.013.514.014.515.015.516.016.5
Ph ase I I Ph ase I I IPh ase IPh ase I Ph ase I IPh ase I I I
*
*
P ha se I P ha se II P ha se III*1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58
Da ys
0
2
4
6
8
10
12
14
16
18
20
EtO
H C
on
sum
pti
on
(g
/kg
/day
)
Tre a tm e nt Control
1 11 21 31 41 51 61 71 81 92 0
*
*
#
#
P ha s e I P ha s e IP ha s e III P ha s e IIIP ha s e II P ha s e II
Tre a tm e nt Control
Pha se I Pha se II Pha se III* #
1 4 7 10 13 16 19 22 25 28 31 34 37 40 43 46 49 52 55 58 61
Da ys
-30
-20
-10
0
10
20
30
40
50
60
Wat
er C
on
sum
pti
on
(g
/kg
/day
)
Control Tre a tm e nt
P ha se I P ha se II P ha se III
Treatmen t C o n tro l
15
20
25
30
35
40
45
50
55
Ph ase I Ph ase I I Ph ase I I I Ph ase I Ph ase I I Ph ase I I I
Young Old
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Consumption and RunningEtOH Water
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EtOH and Water Groups, Comprehensive Charts
Water, EtOH and Sum Correlations with Distance Run
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LL Effects
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Split Rhythms
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Discussion
Exercise decrease fragmentation?Decrease phase shifting in the aged combined with
exerciseChange in activity onset with aging, with comparison
between IR and wheel onsets. Decrease EtOH consumption with running, competitive
reward pathway?Increase water consumption in aged animals combined
with runningExercise and aging:
Decrease in biochemical and neurological pathway substrates?
Inability to quickly replenish depleted substances?Ergogenic aids ?Chronic training; Lessons from Dean?
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Conclusions
Further Research is Needed
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Questions?
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IGL
MRN
RHT
GHT
Light
DRN
Glutamate
NMDA(AMPA
Kainate) receptors
Ca++
PACAPPAC1
VPAC2receptors
Mg++
2nd messengerpathways
c-fosPer1Per2
5-HT 5-HT
NPYGABA
GlutamatePACAP