아주대학교

목차

I. INTRODUCTION 1
1. Overview of Circadian Clock Systems 1
2. The Central Role of sLNv Pacemaker Neurons and PDF Signaling 4
3. Aging-Associated Decline of Circadian Output Signaling 6
4. Metabolic–Circadian Interactions and the Role of Pyruvate Kinase (PYK) 6
5. TARA as a Metabolic–Epigenetic Mediator of PDF Regulation 6
6. Epigenetic Regulation via PHD and Bromodomain Proteins 7
7. Metabolic Reprogramming in Aging and Its Impact on Circadian Output 7
8. Aims of the Thesis: Defining the Metabolic–Circadian Interface in Aging 7
II. MATERIALS AND METHODS 9
1. Fly Stock 9
2. Locomotor Behavior Analysis 9
3. Immunohistochemistry and Confocal Imaging 9
4. Western Blotting 10
5. Statistics and Reproducibility 10
III. RESULTS 12
1. Age-Related Alterations in Survival, Sleep Architecture, and Circadian Period 12
2. Aging Reduces PDF Expression in the Soma and Dorsal Projections of sLNvs and Dorsal Projections of CS Drosophila 15
3. Aging-Dependent Reduction of PDF Expression Occurs in Both CS and w¹¹¹⁸ Drosophila 19
4. Acute Reduction of Pyk Selectively Decreases PDF Levels in sLNv Pacemaker Neurons 24
5. TARA Mediates the Downstream Effect of Pyk on PDF Expression and Circadian Output 26
6. Identification of Chromatin Regulators Acting Downstream of the PYK– TARA–PDF Axis 30
IV. DISCUSSION 34
1. Aging-Dependent Decline of Circadian Pacemaker Function Through Coordinated Loss of PDF and PER Signaling 34
2. Search for Downstream of the PYK–TARA–PDF Axis 35
3. Experimental Limitations and Future Directions 37
V. CONCLUSION 39
VI. REFERENCES 41
국문요약 44