Grant: Foundation Grant

Aging; Endurance Exercise; Exosomes; Neuromuscular Disorders; Proteomics; Rna-Sequencing; Skeletal Muscle; Systemic Humoral Factors; Systemic Mitochondrial Metabolism; Type 2 Diabetes

<html> <body> <p>Studies have shown that regular physical activity reduces the risk of chronic diseases and extends lifespan. The health benefits of exercise are systemic and counteract metabolic dysfunction. The complex array of factors that promote organ cross-talk to mediate the systemic pro-metabolic benefits of exercise have not been fully elucidated. Studies have shown that peptides secreted by skeletal muscle and fat can regulate aspects of exercise adaptations. These results led to our definition of &lsquo;<em>exerkines</em>&rsquo; as the sum total of all factors (peptides, metabolites, mRNA, and miRNA) produced, expressed, and secreted by all tissues/organs that promote organ cross-talk and impart systemic benefits of exercise. Thus the <strong><em>central aim</em></strong> of our research proposal is to use human and murine exercise studies and cell culture model-based approaches with cutting-edge molecular tools to identify and characterize novel humoral factors that modulate the pro-metabolic effects of exercise and to understand the delivery mechanism(s) that mediate organ cross-talk. We have discovered that exosomes mediate most of these systemic benefits and we have a method for their use as protein/gene therapy for genetic disorders. Our goal is to understand the intricacies of molecular exercise physiology to mitigate aging and associated comorbidities to devise exosome based therapies for neuromuscular and neurometabolic genetic disorders that mimic aspects of human aging. The findings are likely to produce high impact publications and presentations, and lead to the development of patents, biotech companies and partnerships to develop therapies for the above mentioned disorders, all of which will strengthen the Canadian economy.<br> <br> Accordingly, in the next seven years we will focus on three broad research goals:<br> <br> <strong>Goal #1.</strong> To understand how the aging process affects the biology of exerkines and exersomes in response to exercise.<br> <br> <strong>Goal #2.</strong> To evaluate the therapeutic potential of exerkines and exersomes in mitigating mitochondrial and metabolic dysfunction in aging and obesity/type 2 diabetes.<br> <br> <strong>Goal #3.</strong> To evaluate the therapeutic potential of bioengineered exosomes in primary genetic diseases that mimic aspects of human aging.<br> <br> To achieve these goals, I have developed the knowledge base, recruited the experts, and established vital collaborations to ensure that my research program has the necessary resources to accomplish proposed goals. My basic science and clinical research laboratory is positioned to make significant discoveries: (i) by having equipped with the state-of-the-science equipment and access to University core facilities, and (ii) staffed with experts in the areas of physiology, genomics, proteomics, metabolomics, cellular and molecular biology of aging and exercise metabolism, and neuromuscular and neurometabolic disorders. In addition, my laboratory and clinic is staffed with experts in the areas of human and murine study design, exosome isolation, cell culture techniques and genetic/proteomic analyses. Finally, I believe that my research program will provide training opportunities for students, postdoctoral fellows, and highly qualified personnel, while building expertise in the areas of exercise physiology, aging and associated comorbidities, and genetic disorders. Personnel supported as a consequence this proposal will gain valuable knowledge and acquire skill set that will stand them in good stead to meet the challenges of careers in academia and/or industry.</p> </body> </html>