Aging of the Genome The Dual Role of DNA in Life and Death

by Vijg, Jan

• ISBN13: 9780198569237
• ISBN10: 0198569238
• Edition: 1st
• Format: Paperback
• Copyright: 2007-03-29
• Publisher: Oxford University Press

Summary

Aging has long since been ascribed to the gradual accumulation of DNA mutations in the genome of somatic cells. However, it is only recently that the necessary sophisticated technology has been developed to begin testing this theory and its consequences. Vijg critically reviews the concept of genomic instability as a possible universal cause of aging in the context of a new, holistic understanding of genome functioning in complex organisms resulting from recent advances in functional genomics and systems biology. It provides an up-to-date synthesis of current research, as well as a look ahead to the design of strategies to retard or reverse the deleterious effects of aging. This is particularly important in a time when we are urgently trying to unravel the genetic component of aging-related diseases. Moreover, there is a growing public recognition of the imperative of understanding more about the underlying biology of aging, driven by continuing demographic change.

Author Biography

Jan Vijg is Professor at the Buck Institute for Age Research in Novato, California, USA

Table of Contents

Preface	p. v
Introduction: the coming of age of the genome	p. 1
The age of biology	p. 2
From genetics to genomics	p. 12
A return to function	p. 17
The causes of aging: a random affair	p. 23
The logic of aging	p. 27
Aging genes	p. 28
Pleiotropy in aging	p. 36
Interrupting the pathways of aging	p. 39
Longevity-assurance genes	p. 47
Somatic damage and the aging genome	p. 52
Genome structure and function	p. 57
DNA primary structure	p. 58
Higher-order DNA structure	p. 71
Nuclear architecture	p. 77
Transcription regulation	p. 81
Conclusions	p. 89
Genome maintenance	p. 91
Why genome maintenance?	p. 93
DNA-damage signaling and cellular responses	p. 98
DNA-repair mechanisms	p. 105
Genome maintenance and aging	p. 140
Genome instability and accerated aging	p. 151
Premature aging	p. 152
Validity of accelerated-aging phenotypes	p. 155
Genome maintenance and accelerated aging in mice	p. 160
Conclusions	p. 177
The aging genome	p. 181
DNA damage	p. 183
DNA-sequence changes	p. 198
Changes in DNA modification and conformation	p. 223
Summary and conclusions: a DNA damage report of aging	p. 229
From genome to phenome	p. 233
The causes of cancer	p. 239
Genome instability and tissue dysfunction	p. 247
Testing the role of genome instability in aging	p. 278
A genomic limit to life?	p. 289
Aiming for immortality	p. 289
SENS, and does it make sense?	p. 293
Epilogue	p. 299
Glossary	p. 301
References	p. 309
Index	p. 353
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