Post on 18-Jan-2016
description
Genes, Environments and Human Development, Health and Genes, Environments and Human Development, Health and DiseaseDisease
ExerciseExercise
Dan M. Cooper MD
Main PointsMain Points
1.1.Exercise is DANGEROUSExercise is DANGEROUS
2.2.Physical activity alters growth and Physical activity alters growth and developmentdevelopment
3.3.Physical activity influences health and Physical activity influences health and disease disease
4.4.Brief bouts of exercise alter leukocyte Brief bouts of exercise alter leukocyte gene expressiongene expression
5.5.The search for “fitness” genes is The search for “fitness” genes is ongoing and complex.ongoing and complex.
1.1. Exercise is DANGEROUSExercise is DANGEROUS
Exercise-induced Exercise-induced anaphylaxisanaphylaxis
“Be honest—how much are you exercising?”
2.2.Physical activity alters growth and Physical activity alters growth and developmentdevelopment
Exercise Growth Hormone
IGF-I
Stimulates local tissues (?IGF-I) directly
Target Tissues
? GH binding
proteins
? IGF binding proteins
? BP Proteolysis
? mechanisms
Change in key growth Change in key growth and stress mediators and stress mediators in 51 healthy, growing, in 51 healthy, growing, premature babies over premature babies over a 4-6 week period in a 4-6 week period in the UCI NICU the UCI NICU
Physical Physical InactivityInactivity
++Diet high in Diet high in
fat and fat and caloriescalories
++Maturational Maturational
StatusStatus++
EnvironmentEnvironmental Factorsal Factors
++Genetic Genetic FactorsFactors
In otherwise healthy children...In otherwise healthy children...
= obesity, metabolic syndrome, asthma, = obesity, metabolic syndrome, asthma, adult cardiovascular disease, canceradult cardiovascular disease, cancer
3. Physical activity influences health and disease3. Physical activity influences health and disease
Physiological Physiological constraintsconstraints
++Abnormal Abnormal
inflammatorinflammatory responsesy responses
++Maturational Maturational
StatusStatus++
EnvironmentEnvironmental Factorsal Factors
++Genetic Genetic FactorsFactors
In children with chronic disease and In children with chronic disease and disability…disability…
= narrow range of optimal exercise= narrow range of optimal exercise
PHYSICAL ACTIVITYPHYSICAL ACTIVITY
Growth Growth MechanismsMechanisms
Stress/Inflammatory Stress/Inflammatory MechanismsMechanisms
Innate and Adaptive Innate and Adaptive ImmunityImmunity•Inflammatory cytokinesInflammatory cytokines•PBMCsPBMCs
Anabolic FactorsAnabolic Factors•Pituitary GHPituitary GH•IGF-I systemIGF-I system
Health Health EffectsEffects
Growth Growth EffectsEffects
““Critical Periods”Critical Periods” EnvironmentEnvironmentGenGenee
Physical Activity, Health, and Growth in Children—Physical Activity, Health, and Growth in Children—Potential MechanismsPotential Mechanisms
??
?? ??
4. Brief bouts of exercise alter 4. Brief bouts of exercise alter leukocyte gene expressionleukocyte gene expression
ExerciseExercise
Possible Mechanisms of Exercise Modulation of Possible Mechanisms of Exercise Modulation of WBC Gene ExpressionWBC Gene Expression
DIRECT EFFECTS:DIRECT EFFECTS:Heat, Hypoxia, Heat, Hypoxia, Acidosis, Acidosis, Catecholamines,IL-6Catecholamines,IL-6
BaselineBaseline
Global SignalGlobal Signal
INDIRECT EFFECTS:INDIRECT EFFECTS:Recruitment of leukocytes Recruitment of leukocytes from depots (lung, from depots (lung, demargination, lymph demargination, lymph tissue, bone marrow)tissue, bone marrow)
Post ExercisePost Exercise
Global SignalGlobal Signal
Leukocytes expressing different genes
Impact of Brief Exercise on Representative PBMC Gene Impact of Brief Exercise on Representative PBMC Gene Expression in Children: A Comparison of RT-PCR vs AffyU133Expression in Children: A Comparison of RT-PCR vs AffyU133
0 1 2 3 4 50.0
0.5
1.0
1.5
2.0
2.5
AffyU133 (peak/base)
RT
-PC
R (
pea
k/b
ase)
HSPA1BHSPA1B
HSPA8HSPA8
CTSWCTSW
GRZBGRZB
CASP6CASP6
TBX21TBX21
R=0.90R=0.90
EnvironmenEnvironmentt
GenotypeGenotype
PhenotypPhenotypee
Previous ApproachPrevious Approach
EnvironmenEnvironmentt
GenotypeGenotype
Emerging Emerging ApproachApproach
PhysiologicPhysiological al
ChallengeChallenge
Regulatory Regulatory ResponseResponse
IntermediatIntermediate e
PhysiologicaPhysiologicall
PatternsPatterns
Thanks for your attention!Thanks for your attention!
We would like to acknowledge the NIH support for this work:We would like to acknowledge the NIH support for this work:
UCI GCRC--MO1 RR00827, RO1 NHLBI 080947, PO1 NICHD UCI GCRC--MO1 RR00827, RO1 NHLBI 080947, PO1 NICHD 048721 048721