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Genes, Environments and Human Development, Health and Disease

Genes, Environments and Human Development, Health and Disease. Exercise Dan M. Cooper MD. Main Points Exercise is DANGEROUS Physical activity alters growth and development Physical activity influences health and disease Brief bouts of exercise alter leukocyte gene expression

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Genes, Environments and Human Development, Health and Disease

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  1. Genes, Environments and Human Development, Health and Disease Exercise Dan M. Cooper MD

  2. Main Points • Exercise is DANGEROUS • Physical activity alters growth and development • Physical activity influences health and disease • Brief bouts of exercise alter leukocyte gene expression • The search for “fitness” genes is ongoing and complex.

  3. 1.Exercise is DANGEROUS Exercise-induced anaphylaxis

  4. “Be honest—how much are you exercising?” • Physical activity alters growth and development

  5. Exercise Growth Hormone ? mechanisms ? GH binding proteins Stimulates local tissues (?IGF-I) directly IGF-I ? IGF binding proteins ? BP Proteolysis Target Tissues

  6. Change in key growth and stress mediators in 51 healthy, growing, premature babies over a 4-6 week period in the UCI NICU

  7. 3. Physical activity influences health and disease In otherwise healthy children... Physical Inactivity + Diet high in fat and calories + Maturational Status + Environmental Factors + Genetic Factors = obesity, metabolic syndrome, asthma, adult cardiovascular disease, cancer

  8. In children with chronic disease and disability… Physiological constraints + Abnormal inflammatory responses + Maturational Status + Environmental Factors + Genetic Factors = narrow range of optimal exercise

  9. Physical Activity, Health, and Growth in Children—Potential Mechanisms PHYSICAL ACTIVITY Growth Mechanisms Stress/Inflammatory Mechanisms ? • Anabolic Factors • Pituitary GH • IGF-I system • Innate and Adaptive Immunity • Inflammatory cytokines • PBMCs ? ? “Critical Periods” EnvironmentGene Growth Effects Health Effects

  10. 4. Brief bouts of exercise alter leukocyte gene expression

  11. Possible Mechanisms of Exercise Modulation of WBC Gene Expression Leukocytes expressing different genes Baseline Post Exercise DIRECT EFFECTS: Heat, Hypoxia, Acidosis, Catecholamines,IL-6 Exercise INDIRECT EFFECTS: Recruitment of leukocytes from depots (lung, demargination, lymph tissue, bone marrow) Global Signal Global Signal

  12. HSPA1B HSPA8 TBX21 CTSW GRZB CASP6 Impact of Brief Exercise on Representative PBMC Gene Expression in Children: A Comparison of RT-PCR vs AffyU133 R=0.90

  13. Environment Genotype Phenotype Previous Approach

  14. Environment Genotype Emerging Approach Physiological Challenge Regulatory Response phenotype Intermediate Physiological Patterns

  15. Thanks for your attention! We would like to acknowledge the NIH support for this work: UCI GCRC--MO1 RR00827, RO1 NHLBI 080947, PO1 NICHD 048721

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