[...]... culminated in Darwin’s theory of evolution by natural selection and Watson and Crick’s discovery of the molecular structure of DNA The grand understanding of the logic of life would prove equally important for understanding its demise: the logic of aging Before the seventeenth century our state of knowledge was static and, in Western Europe, mainly based on a synthesis of the Greek–Roman heritage and the. .. CONTENTS 6 The aging genome 181 6.1 6.2 6.3 6.4 183 198 223 229 DNA damage DNA- sequence changes Changes in DNA modification and conformation Summary and conclusions: a DNA damage report of aging 7 From genome to phenome 233 7.1 The causes of cancer 7.2 Genome instability and tissue dysfunction 7.3 Testing the role of genome instability in aging 239 247 278 8 A genomic limit to life? 289 8.1 Aiming for... provided the starting points of how we hope to gain a more complete understanding of how life forms are ordered at the molecular level and how this order turns into disorder during aging 1.1 The age of biology With physics and chemistry at their zenith in the nineteenth and twentieth centuries, biology, the study of life, is often considered the premier science of the century we have just entered, with the. .. the same source: the invention of the microscope in the new INTRODUCTION 3 permissive era of the Renaissance, which allowed for the first time a detailed observation of the various manifestations of life A dual quest began to discover life in all its splendid variability and to find out the details of its workings Along these parallel paths of studying why life is and how it works, the science of aging. .. rapidly achieving, say, a doubling of human lifespan? As I will try to argue in this book, the answers to these questions may be hidden in the genome The rapid rise of modern biology is very much the story of the coming of age of the genome, the complete set of genetic information of an organism Genome research has not only provided us with our current basic understanding of the logic of life, but has... genetic mutation Charles Darwin and Alfred Wallace propose natural-selection theories of evolution The International Human Genome Sequencing Consortium publishes the complete draft of the human genome sequence 1 Introduction: the coming of age of the genome Science and technology extend life and improve the quality of life Whereas in a sense this may have been true since the origin of Homo sapiens, it has... be a function of the distance between genes on the chromosome The smaller that distance, the greater their chance of being inherited together, whereas the farther away they are from each other, the more chance of their 6 INTRODUCTION being separated by the process of crossing over The Morgan is now the unit of measurement of distances along all chromosomes in fly, mouse, and human In the meantime, cytologists... understanding of life, and the emergence of functional genomics and systems biology 1.2 From genetics to genomics In the heydays of molecular biology it seemed natural to begin our effort of understanding the structure and function of various life forms with understanding individual genes and their activities in different organisms Indeed, after Watson and Crick, the central dogma may have clarified the. .. history of biology the discovery of the logic of life was followed by an understanding of the logic of aging Following Weismann’s original non-adaptive concepts of explaining aging, most researchers now accept that aging is ultimately due to the greater relative weight placed by natural selection on early survival or reproduction than on maintaining vigor at later ages This decline in the force of natural... provided the insight that proteins were the workhorses of biological systems, and DNA the carrier of genetic information, organized in the form of a genome Genes were shown to be specific sequences of base pairs that contain the instructions, in the form of a triplet code, for making proteins Interestingly, not long after the discovery of the fundamental mechanism of protein biosynthesis, Leslie E Orgel (San . alterations in the DNA of the genome in the cells of our body. This theory has proved to be remarkably robust and is compatible with the other major theory of aging that does not die: the free-radical theory. return to function 17 1.4 The causes of aging: a random affair 23 2 The logic of aging 27 2.1 Aging genes 28 2.2 Pleiotropy in aging 36 2.3 Interrupting the pathways of aging 39 2.4 Longevity-assurance. disposable soma theory Aging of the Genome: timeline 1 Introduction: the coming of age of the genome Science and technology extend life and improve the quality of life. Whereas in a sense this may