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Template: Front Matter Effects of fatty acid supplementation on gene expression, lifespan, and biochemical changes in wild type and mutant C. elegans strains by Amal Bouyanfif, MSc, BSc A Dissertation In Plant and Soil Science Submitted to the Graduate Faculty of Texas Tech University in Partial Fulfillment of the Requirements for the Degree of DOCTOR OF PHILOSOPHY Approved Dr. Eric Hequet Chair of Committee Dr. Naima Moustaid-Moussa Co-chair Dr. Michael Ballou Dr. Latha Ramalingam Dr. Venugopal Mendu Dr. Iurii Koboziev Mark Sheridan Dean of the Graduate School August, 2019 Copyright 2019, Amal Bouyanfif Texas Tech University, Amal Bouyanfif, August 2019 DEDICATION Every challenging work requires self-effort as well as guidance and support of those who are close to our heart. I dedicate this dissertation to my husband, my kids, and my family. To my husband, Noureddine, because you believed in me, you encouraged me, and you were with me in every step since we met. Without your support, I would never have begun this journey. To my kids, Merwan & Nabil, you were very patient with me, you will always be my greatest achievement and I am so proud of you. You are such a blessing to me and I love you so much. To my parents and my family for their love and constant support even if thousands of miles separate us. ii Texas Tech University, Amal Bouyanfif, August 2019 ACKNOWLEDGMENTS First, I would like to thank my advisors, Dr. Naima Moustaid-Moussa and Dr. Eric Hequet for guiding me throughout my dissertation. Dr. Moustaid-Moussa invited me into her laboratory, allowed me to work on this research project, and advised me during this research. I would like to express my gratitude to all lab members who helped me during my research specially Drs. Latha Ramalingam, Iurii Koboziev, and Sumedha Liyanage. I would like to thank my committee members, Dr. Michael Ballou, Dr. Venugopal Mendu, Dr. Latha Ramalingam, and Dr. Iurii Koboziev for serving on my dissertation committee. I would like also to thank Dr. Seshardi Ramkumar for accepting to serve as Dean’s representative. The work described in this research was initiated through a collaboration with Chemical Engineering Department at Texas Tech University. As such, I would like to acknowledge and thank Dr. Siva Vanappali for allowing me to train in his laboratory and Jennifer Hewitt who provided me with the training I needed to start this C. elegans research in Dr. Moustaid-Moussa’s lab. I would like to knowledge the partial financial support from Texas Tech University Graduate School, the United States Department of Agriculture, and the Fiber and Biopolymer Research Institute. Finally, I am most grateful to my husband and kids who supported me throughout this process. Without their love and support, I would never have been able to finish this work. iii Texas Tech University, Amal Bouyanfif, August 2019 TABLE OF CONTENTS Dedication ............................................................................................................... ii Acknowledgments .................................................................................................. iii Abstract ................................................................................................................ viii List of Tables.......................................................................................................... ix List of Figures ......................................................................................................... x Abbreviations ........................................................................................................ xv General Introduction and overview ......................................................................... 1 References ....................................................................................................... 5 1. The nematode C. elegans as a model organism to study metabolic effects of omega 3 polyunsaturated fatty acids in obesity .................................. 8 1.1. Abstract ........................................................................................... 8 1.2. Introduction to the limitations of current omega-3 fatty acid research due to imperfect model organisms .................................... 9 1.3. Overview of polyunsaturated fatty acids, and their lipid mediators ....................................................................................... 13 1.4. Beneficial effect of omega-3 polyunsaturated fatty acids and mechanisms mediating their effects in mammals ......................... 17 1.5. Review of the C. elegans as a model organism and its advantages ..................................................................................... 23 1.6. Related research on omega-3 fatty acid metabolism that has been conducted in C elegans and knowledge gained .................... 29 1.7. Role of microRNAs in mediating nutritional and obesity- related effects in C. elegans and in other animal models .............. 34 1.8. Conclusions and future direction of the field ................................ 39 1.9. References ..................................................................................... 40 2. Translational aging research in Caenorhabditis elegans .................................. 53 2.1. Abstract ......................................................................................... 53 2.2. Overview of aging ......................................................................... 54 2.3. Oxidative Stress and Reactive Oxygen Species theory of aging .............................................................................................. 56 2.4. C. elegans applications in aging studies ....................................... 58 2.4.1. Introduction to C. elegans ............................................................. 58 2.4.2. Lifespan studies in C. elegans ....................................................... 64 iv Texas Tech University, Amal Bouyanfif, August 2019 2.5. Signaling pathways that modulate aging in C. elegans................. 68 2.5.1. Insulin/IGF-1/FOXO pathway ...................................................... 68 2.5.2. AMP-activated kinase ................................................................... 74 2.5.3. Target-of-rapamycin pathway ....................................................... 74 2.5.4. Germline signaling ........................................................................ 75 2.5.5. Autophagy ..................................................................................... 78 2.6. Cellular and epigenetic mechanisms of aging in C. elegans ......... 79 2.6.1. Lipid metabolism and energy ........................................................ 79 2.6.2. MicroRNA and histone modification ............................................ 80 2.7. Genetic and environmental interventions influence longevity...... 82 2.7.1. Dietary restriction.......................................................................... 82 2.7.2. Bioactive phytomolecules ............................................................. 85 2.7.2.1. Resveratrol .................................................................................... 87 2.7.2.2. Polyphenols and Epigallocatechin gallate (EGCG) ..................... 87 2.7.2.3. Beta-caryophellene ....................................................................... 88 2.7.2.4. Alkaloids ........................................................................................ 89 2.7.2.5. Curcumin ....................................................................................... 89 2.7.2.6. Polyunsaturated fatty acids ........................................................... 90 2.8. Conclusions ................................................................................... 93 2.9. References ..................................................................................... 95 3. Review of FTIR microspectroscopy applications to investigate biochemical changes in C. elegans ................................................................. 122 3.1. Abstract ....................................................................................... 122 3.2. Introduction ................................................................................. 123 3.3. FTIR applications for nematode research ................................... 125 3.3.1. FTIR FPA imaging of whole nematode ...................................... 125 3.3.2. Nematode identification .............................................................. 129 3.3.3. Diet and genotype-dependent changes in chemical composition ................................................................................. 130 3.3.4. Biochemical composition ............................................................ 135 3.3.5. Toxicity assessment .................................................................... 138 3.4. Conclusions and perspectives ..................................................... 139 3.5. References ................................................................................... 141 4. Effects of eicosapentaenoic acid on Caenorhabditis elegan’s lifespan and gene expression ........................................................................................ 147 4.1. Abstract ....................................................................................... 147 4.2. Introduction ................................................................................. 148 4.3. Materials and methods ...............................................................
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