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Nutrigenomics and Aging: a Transcriptomic Perspective

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Nutrigenomics and Aging: a Transcriptomic Perspective Iowa State University Capstones, Theses and Graduate Theses and Dissertations Dissertations 2020 Nutrigenomics and aging: A transcriptomic perspective Joe Lawrence Webb Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/etd Recommended Citation Webb, Joe Lawrence, "Nutrigenomics and aging: A transcriptomic perspective" (2020). Graduate Theses and Dissertations. 18244. https://lib.dr.iastate.edu/etd/18244 This Dissertation is brought to you for free and open access by the Iowa State University Capstones, Theses and Dissertations at Iowa State University Digital Repository. It has been accepted for inclusion in Graduate Theses and Dissertations by an authorized administrator of Iowa State University Digital Repository. For more information, please contact [email protected]. Nutrigenomics and aging: A transcriptomic perspective by Joseph Lawrence Webb A dissertation submitted to the graduate faculty in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY Major: Nutritional Sciences Program of Study Committee: Matthew Rowling, Co-major Professor Elizabeth McNeill, Co-major Professor Andrew Bolstad Anumantha Kanthasamy Kevin Schalinske Peter Clark The student author, whose presentation of the scholarship herein was approved by the program of study committee, is solely responsible for the content of this dissertation. The Graduate College will ensure this dissertation is globally accessible and will not permit alterations after a degree is conferred. Iowa State University Ames, Iowa 2020 Copyright © Joseph Lawrence Webb, 2020. All rights reserved. ii TABLE OF CONTENTS Page LIST OF FIGURES .........................................................................................................................v LIST OF TABLES ......................................................................................................................... vi NOMENCLATURE ..................................................................................................................... vii ABSTRACT .................................................................................................................................. xii CHAPTER 1. GENERAL INTRODUCTION ................................................................................1 General Introduction .................................................................................................................. 1 Dissertation Organization .......................................................................................................... 3 Authors’ Roles ........................................................................................................................... 4 References ................................................................................................................................. 5 CHAPTER 2. LITERATURE REVIEW .........................................................................................6 Chronic Disease Prevalence ................................................................................................. 6 Nutrigenomics: The Role of Diet Modifying the Transcriptome ......................................... 8 Whole Eggs Impact on Health & Disease .......................................................................... 10 Composition of Whole Eggs & Bioactive Mechanisms of Action .................................... 11 Diabetes, Eggs, & Gene Expression ................................................................................... 15 Relationship Between Whole Eggs & Neurodegeneration ................................................ 16 Impact of Aging on the Transcriptome .............................................................................. 18 Comparative Aging Across Species ................................................................................... 22 Aging Associated Diseases & Dysregulation of the Transcriptome .................................. 24 Predicting Chronological Aging ......................................................................................... 26 Role of MicroRNAs in Health & Disease .......................................................................... 29 References .......................................................................................................................... 32 CHAPTER 3. LARGE AND SMALL RNA SEQUENCING REVEALS OXIDATIVE- REDUCTION PATHWAYS ARE MODIFIED BY SHORT-TERM WHOLE EGG CONSUMPTION ...........................................................................................................................53 Abstract .................................................................................................................................... 54 Introduction ............................................................................................................................. 55 Methods ................................................................................................................................... 56 Animals and Diets .............................................................................................................. 56 Large and small RNA Extraction & Sequencing ............................................................... 57 Quality Control & Adapter Trimming................................................................................ 58 Read Alignment & Quantification ..................................................................................... 58 Data Filtering & Quality Control ....................................................................................... 58 Differential Expression Analysis using DESeq2................................................................ 59 Heatmaps, Principal Component Analysis, & Volcano Plots ............................................ 59 Functional Enrichment Annotations ................................................................................... 59 qRT-PCR Validation Analyses .......................................................................................... 60 iii Results ..................................................................................................................................... 61 RNA Seq Differential Expression ...................................................................................... 61 KEGG & GO Functional Enrichment Analysis ................................................................. 61 MicroRNA Sequencing Differential Expression Analysis ................................................. 62 MicroRNA Gene Target Analysis ...................................................................................... 62 Serum MicroRNA Refeeding Analysis .............................................................................. 62 Principal Component Analysis (PCA) & Hierarchical Clustering ..................................... 63 qRT-PCR validation ........................................................................................................... 63 Protein-protein Interaction Networks ................................................................................. 63 Food Intake & Body Weight Gain ..................................................................................... 63 Discussion ................................................................................................................................ 64 Conclusions ............................................................................................................................. 69 References ............................................................................................................................... 70 Tables & Figures ..................................................................................................................... 75 CHAPTER 4. WHOLE EGG CONSUMPTION INCREASES GENE EXPRESSION WITHIN THE GLUTATHIONE PATHWAY IN THE LIVER OF ZUCKER DIABETIC FATTY RATS ...............................................................................................................................98 Abstract .................................................................................................................................... 99 Background: ............................................................................................................................. 99 Methods: .................................................................................................................................. 99 Results: .................................................................................................................................... 99 Conclusion: ............................................................................................................................ 100 Introduction ........................................................................................................................... 100 Methods ................................................................................................................................. 101 IACUC Approval ............................................................................................................. 101 Animal Housing & Experimental Design ........................................................................ 101 RNA Extraction & Analysis ............................................................................................. 102 SmallRNA & TotalRNA Sequencing .............................................................................
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