Aging of the Genome.

Aging has since long 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. In this book the concept of genomic instability as a possible universal cause of aging is critically reviewed 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 describes how aging is intertwined with evolution by natural selection and why mutations in the genome of somatic cells provide a logical explanation of how we age. The book provides details about how mutations arise in the genome of somatic cells through errors during the repair of the very large amounts of DNA damage, such as breaks or chemical adducts, that are the result of environmental agents or by-products of normal metabolism. Since in contrast to all other macromolecules the DNA of our genome cannot be replaced, mutations are irreversible, gradually weakening the genetic information our cells rely on to provide function. The book shows how mutations can give rise to age-related diseases, such as cancer, and can also cause functional decline. It tries to address the question how mutation accumulation can be slowed down, thereby preventing or retarding the deleterious effects of aging. This is critically important in view of the growing public recognition of the need to understand more about the underlying biology of aging, driven by continuing demographic change. The book has been reviewed by both Nature (Partridge L, Nature 447, pp 262-263, 2007) and Nature Genetics (Bohr VA and Bohr CT, Nature Genetics 39, pp 1291, 2007), the two top scientific journals in the field.