E-Book Overview
Aging occurs at the level of individual cells, a complex interplay between intrinsic "programming" and exogenous "wear and tear", with genetically-determined cellular capacity to repair environmentally-induced DNA damage playing a central role in the rate of aging and its specific manifestations. In 12 chapters, "The Role of DNA Damage and Repair in Cell Aging" provides an intellectual framework for aging of mitotic and post-mitotic cells, describes a variety of model systems for further studies, and reviews current concepts of DNA responses and their relationship to the phenomenon of aging.As part of a series entitled "Advances in Cell Aging and Gerontology," this volume also summarizes seminal recent discoveries such as the molecular basis for Werner syndrome (a mutant DNA helicase), the complementary roles of telomere shortening and telomerase activity in cell senescence versus immortalization, the role of apoptosis in the homeostasis of aging tissue, and the existence of an inducible SOS-like response in mammalian cells that minimizes DNA damage from repeatedly encountered injurious environmental agents. Insights into the relationship between cellular aging and age-associated diseases, particularly malignancies, are also provided in several chapters.This book is an excellent single source of information for anyone interested in DNA repair, mechanisms of aging, or certainly their intersection. Students will gain a general appreciation of these fields, but even the most senior investigators will benefit from the detailed coverage of rapidly advancing areas.
E-Book Content
INTRODUCTION
Nearly 40 years ago it was demonstrated that aging occurs at the level of individual cells. In the intervening decades, a complex interplay between intrinsic "programming" and exogenous "wear and tear" has become apparent, with genetically-determined cellular capacity to repair environmentally-induced DNA damage playing a central role in the rate of aging and its specific manifestations. In 12 chapters, "The Role of DNA Damage and Repair in Cell Aging" provides an intellectual framework for aging of mitotic and post-mitotic ceils, describes a variety of model systems for further studies, and reviews current concepts of DNA damage responses and their relationship to the phenomenon of aging. As part of a series entitled "Advances in Cell Aging and Gerontology," this volume also summarizes seminal recent discoveries such as the molecular basis for Werner syndrome (a mutant DNA helicase), the complementary roles of telomere shortening and telomerase activity in cell senescence versus immortalization, the role of apoptosis in the homeostasis of aging tissue, and the existence of an inducible SOS-like response in mammalian cells that minimizes DNA damage from repeatedly encountered injurious environmental agents. Insights into the relationship between cellular aging and ageassociated diseases, particularly malignancies, are also provided in several chapters. Whereas most of the early work on DNA repair pathways involved DNA lesions caused by environmental factors such as UV irradiation, there is now very active research on the DNA repair processes involved in the removal of oxidative DNA lesions that result, for example, from intracellular metabolism and presumably impact on "the rate of living." Many studies have shown that the frequency of oxidative DNA lesions increase with age in mammalian systems, and this could be due to increased formation and/or decreased repair of these lesions. Persistent lesions in the genome could explain many of the characteristics of the molecular pbenotype of aging, such as the changes in transcription and the significantly increased genomic instability, issues touched upon throughout the volume. The molecular biology of aging has surely come of age, lending its powerful techniques to the dissection of pathways re