Front Cover

Telomeres in Health and Disease

Copyright

Contents

Contributors

Preface

Chapter One: Telomere and Telomerase Biology

1. Introduction

2. The General Structure of Telomeric DNA

2.1. Telomere loops and G-quartets: Specialized structures at the ends of eukaryotic chromosomes

3. Replication of Telomeres

3.1. The telomerase RNP complex

3.1.1. The reverse transcriptase component

3.1.2. Telomerase accessory factors

3.1.3. The telomerase RNA component

3.1.4. How telomeres are replicated by telomerase

3.1.5. Regulation of telomerase activity in mammals

3.2. Telomere replication in the absence of telomerase

4. Telomeric Chromatin: Implications for End Protection, Telomere Replication, and Telomere Length Regulation

4.1. CST: The major telomere end-binding complex on eukaryotic telomeres

4.2. Shelterin: A conserved, double-stranded, telomeric protein complex that associates with the telomere end-binding CST ...

5. TERRA: The Telomeric RNA Transcript

6. Consequences of Telomere Deprotection

Acknowledgments

References

Chapter Two: Human Telomeres and Telomere Biology Disorders

1. Introduction

2. Telomere Biology in Humans

2.1. Telomeric structure

2.2. Telomerase and telomere-associated proteins

2.3. Alternative lengthening of telomeres

2.4. Measuring TL

3. What Is a TBD?

4. Clinical Features of the TBDs

4.1. Dyskeratosis congenita

4.2. Hoyeraal-Hreidarsson syndrome

4.3. Revesz syndrome

4.4. Coats plus syndrome/CRMCC

4.5. Aplastic anemia

4.6. Pulmonary fibrosis

4.7. Nonalcoholic/noninfectious liver disease

4.8. Genetic anticipation

5. Germ-Line Genetics of TBDs

6. Diagnosing TBDs

7. Genetic Counseling Considerations

8. Clinical Management

8.1. Bone marrow failure

8.2. Pulmonary fibrosis

9. Summary and Future Directions

Acknowledgments

References

Chapter Three: Telomere Biology in Stem Cells and Reprogramming

1. Introduction

1.1. A variety of stem cells throughout organismal development

1.2. Telomeres cap chromosomal ends

2. Telomere Homeostasis in Stem Cells

2.1. Telomerase activity in pluripotent stem cells

2.2. Telomerase activity in adult multipotent cells

2.2.1. Hematopoietic system

2.2.2. Hair follicle stem cells

2.2.3. Intestinal stem cells

2.2.4. Muscle stem cells

2.2.5. Neural stem cells

2.2.6. Spermatogonial stem cells

2.3. Organismal consequences of telomere attrition in stem cells

2.4. Noncanonical roles of telomerase in stem cell regulation

3. Cellular Reprogramming

3.1. Somatic cell nuclear transfer and cell fusion

3.1.1. Telomere biology in SCNT

3.2. Reprogramming through induced pluripotency

3.2.1. Telomere reprogramming in iPS cells

3.2.2. Derivation of IPS cells harboring disease-associated telomerase mutations

4. Conclusions

References

Chapter Four: Telomere Dynamics and Aging

1. Introduction: Telomere Structure, Determinants of Telomere Dynamics, Measurement Parameters, and Regulation Mechanisms

1.1. About this chapter

1.2. Telomere structure and determinants of telomere dynamics

1.3. Measurement parameters, regulation mechanisms, natural variability, and natural variants

2. Telomere Connection to the Characteristics of Aging: Cell Senescence and Apoptosis, Mitochondrial Function, and Metabolism

2.1. Senescence or apoptosis telomere checkpoint

2.2. Telomeres, mitochondrial function, and metabolism

3. Telomeres Dynamics in Early Embryonic Development, Stem Cells, and Infancy

3.1. Gametes, embryogenesis, and stem cells

3.2. Inherited telomere length and dynamics in infancy

4. Telomere Dynamics and Aging-Related Disorders

4.1. Telomere deficiency syndromes

4.2. Genomic instability and cancer

5. Perspective

Acknowledgments

References

Chapter Five: Telomeres in Molecular Epidemiology Studies

1. Introduction

2. TL in Accessible Tissue as a Surrogate for the Disease Site

3. Considerations in Observational Studies of TL

4. Epidemiological Evaluation of the Role of Telomeres in Human Health

5. The Effect of TL Method of Measurement on Study Results

6. Analytic Considerations in TL Epidemiology Studies

7. Conclusions

Acknowledgment

References

Chapter Six: Telomere Dysfunction and Hematologic Disorders

1. Introduction

2. Bone Marrow Failure

3. Dyskeratosis Congenita

4. Disease Anticipation

4.1. Abnormal rRNA modification and dyskerin function

5. Aplastic Anemia

6. Clinical Management in Bone Marrow Failure Syndromes

7. Telomere Shortening in Other Bone Marrow Failure Syndromes

8. Animal Models

9. Telomeres and Hematologic Cancers

References

Chapter Seven: The Role of Telomeres in Liver Disease

1. Telomeres and Telomerase, an Overview

2. Telomere Shortening and Disease Progression

3. The Role of Telomere Dysfunction in Cirrhosis Formation

4. Association of Telomerase Mutations With Liver Cirrhosis

5. The Role of Telomeres in Metabolic Liver Disease

6. The Role of Telomeres During Carcinogenesis

7. Chromosomal Instability and Hepatocarcinogenesis

8. Telomere Dysfunction Promotes Hepatocarcinogenesis

9. Conclusion

Conflict of Interests

References

Chapter Eight: Telomeres in Lung Diseases

1. Introduction

2. Idiopathic Pulmonary Fibrosis

3. Telomeres and Emphysema

4. Telomeres and Development of Lung Disease

5. Conclusions

References

Index

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