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UCI is in the midst of many exciting developments in the area of pediatric pulmonary research. Dr.
Dan Cooper has recently received a large grant to open California's first Pediatric Exercise Research Center.
An article on this story is featured on UCI Today.
Such a center is very much needed to investigate the role of exercise in the physical well-being of healthy and unhealthy children. While the idea that “exercise is good for children” seems axiomatic, translating this vague notion into specific, scientifically based guidelines that actually influence health has proved to be difficult. Never before has the need for such guidelines been so great. We find ourselves in the midst of an emerging epidemic of pediatric obesity, type 2 diabetes, and the metabolic syndrome (a constellation of pathologies consisting of obesity, dyslipidemia, hypertension and insulin resistance), all, in large measure, ominous consequences of unprecedented levels of physical inactivity in children. Concurrently, the incidence of asthma in children, the most prevalent chronic disease of childhood, is increasing, and exercise induced asthma, a common trigger for bronchoconstriction, results in lower levels of physical activity in asthmatic children during a critical stage of their growth and development. Therapeutic advances have created an increasing number of childhood survivors of premature birth, congenital heart disease, lung disease, burn injury, and cancer. For these children, physical activity is beneficial, but only if the “exercise dose” does not exacerbate underlying inflammatory, metabolic, or physiological abnormalities.
These seemingly disparate clinical effects reflect what we now know to be the paradoxical ability of exercise to stimulate a robust stress/inflammatory response characterized by increases in circulating peripheral blood mononuclear cells (PBMCs) and both anabolic and catabolic, pro- and anti-inflammatory mediators, many of which are produced by the PBMCs themselves. This phase of our research is focused on examining for the first time in children the molecular mechanisms of this conundrum in PBMCs, the cells that are emerging as the pivotal interface between physical activity, growth, and disease pathogenesis in children.
The broad theme of research in our laboratory is to understand how physical activity influences growth and development in newborns, children, and adolescents. A major premise has been that physical activity is mechanistically linked to anabolic function through the growth hormone-insulin-like growth factor-I axis (GH®IGF-I), a system of growth mediators, receptors, and binding proteins that control somatic and tissue growth in many species. Recent data indicate that an increased level of physical activity simultaneously stimulates both anabolic and catabolic pathways, the latter, we believe, mediated by the inflammatory cytokines interleukin-1b (IL-1b), IL-6, and tumor necrosis factor-a (TNF-a). Our goal is to begin to delineate the mechanisms underlying these paradoxes by focusing on genomic and proteomic responses of neutrophils and peripheral blood mononuclear cells in children in response to exercise.
We will attempt to understand the mechanisms of growth that continue to function despite the catabolic environment associated with exercise. Moreover, we will begin to identify the boundaries and the physiologic mechanisms involved in “growth versus growth plus exercise” paradigms that play so important a role in determining the optimal levels of physical activity in both healthy children and children with chronic diseases. A very exciting bit of biology for us is that we now have demonstrated that exercise stimulates the immune system, both cytokines and leukocytes even in healthy children. We believe the implications of this discovery for both healthy children and those suffering from chronic diseases and disabilities could be substantial.
We have had the great good fortune to receive an NIDDK grant as one of the nationally selected PIs of an effort to develop school-based programs to prevent type 2 diabetes in children. Our grant was a collaborative effort among UCI, USC, and Children’s Hospital of Los Angeles. The
recent increase in the incidence of type 2 diabetes in children and adolescents is an alarming manifestation of the broader problem of physical inactivity, poor diet, and obesity afflicting young people throughout the world. The development of frank diabetes in children and adolescents will be associated with intensive and costly medical therapy, and long-term chronic disease is almost certain. A preventive strategy that breaks the cycle of physical inactivity and obesity in children would accomplish two goals: 1) reduce the incidence of type 2 diabetes during childhood, adolescence, and adulthood; and 2) lessen the long-term risk of cardiovascular disease and other obesity/diabetes complications.
New collaborations have been developed between our laboratory and the UCI Center for Microarray DNA Analysis under the direction of Dr. Wes Hatfield and the UCI Immunology Center under the leadership of Dr. Paolo Casali. Casali, Hatfield, and I have submitted a Program Project Grant application entitled, “Mechanisms of Health Effects of Exercise in Children”. We have completed a series of original studies testing the effect of exercise on gene expression of peripheral blood mononuclear cells using microarray analysis in human subjects. Equally exciting is our collaboration with nurses in the UCI NICU where we have successfully begun a series of projects focused on the use of exercise in premature babies to enhance weight gain and bone maturation.
Other current projects include:
Dan M. Cooper, M.D.
Professor, Division Chief
Dr. Cooper is the principal investigator in several research projects in the area of pediatric pulmonology. They include:
1. "PBMCs, Exercise, and Children: Initial Mechanisms"
The goal of this project is to understand the effect of brief bouts of exercise on gene and protein expression of
key inflammatory and growth mediators in peripheral blood mononuclear cells in healthy children.
2. "Exercise Strategy to Prevent Pediatric Type 2 Diabetes"
The major goal of this research is to introduce an innovative approach to increase physical activity in schools,
and thereby decrease risk factors for Type 2 Diabetes in children and adolescents. The research is also aimed at
understanding the fundamental inter-relationships among fitness, body composition, and physiological markers of
glucose homeostasis in growing children.
3. "Assisted Exercise in Prematurity: Effects and Mechanisms"
This research is designed to examine the mechanisms through which physical activity in premature babies alters
body composition, immune function, and growth factors.
4. "Mechanisms of Health Effects of Exercise in Children"
This research involves both human and animal models to examine the molecular immune and growth factor mechanisms
through which physical activity alters asthma and metabolic syndrome in children.
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