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Cellular AGING AND CELL DEATH Edited by Nikki J. Holbrook, George R. Martin, and Richard A.Lockshin Cellular Aging and Cell Death provides a thorough understanding ofthe mechanisms responsible for cellular aging, covering the recentresearch on programmed cell death and senescence, and describingtheir role in the control of cell proliferation and the agingprocess. This one-of-a-kind book is the first to combine the twohottest research areas of cell biology into one comprehensivetext. Leading experts contribute to give readers an authoritativeoverview of the distinct fields of cellular aging and programmedcell death, as well as to demonstrate how both fields are criticalto understanding the aging process. They address the large andgrowing interest in apoptosis, especially with regard to themolecular signals that induce and regulate programmed cell death,and the role of apoptosis in a variety of age-associated diseasesand disabilities. Throughout the book, a strong emphasis is placedon the interrelationship of the molecular, cellular, andphysiological aspects of senescence. Individual chapters discuss such topics as the role and regulationof apoptosis in development, the potential impact of cell death onsuch postmitotic tissues as nerve and muscle, and suggest thatprogrammed cell death plays an important role in both pathologicaland nonpathological aspects of aging, including neurodegenerativediseases. One important chapter focuses on the most recent research involvingthe study of telomeres, whose reduction in length with age and celldivision may underlie cellular senescence. The subject of neuronalcell death is also put into the perspective of aging. Cellular Aging and Cell Death bridges the rapidly growing fields ofcellular aging and programmed cell death. This thorough, yetconcise book will be of particular interest to graduate studentsand researchers within the fields of cell and developmentalbiology, neurobiology, immunology, and physiology. Physicians andmedical students involved in the fields of gerontology andpathology will also find this an informative reference.
This book provides updated knowledge on the basic features and mechanisms of cellular aging established since its first manifestation at cellular level 40 years ago. Contributions of genetic and environmental factors, failure of genetic and cellular repair mechanisms, and the epigenetic modifications determine the final lifespan of cells. This book also provides an understanding on how aging mechanisms in mice, a most frequently used model, differ with that of humans who receive better tumor surveillance because of stringent controls on aging mechanisms. It also appraises the use of modern technology for aging studies and its intervention. This book serves as an excellent reading on cellular aging for undergraduate students, researchers and experts of this area.
Time, Cells, and Aging, 2nd Edition presents the mechanics of cell function and the relevant implications of the molecular-genetic view to the aging phenomena. This book explores the biology of the aging process. Comprised of 11 chapters, this edition starts with an overview of the causes and mechanisms underlying the gradual deterioration of structure and function characteristics of aging. This text then examines the two aspects of the behavior of man, including the reasoned conscious behavior and the greater dependence on reaction patterns predicted on the successful responses of the past. Other chapters explore the relationship between aging and mortality rate in animals, which is a result of an organism's deceasing ability to function optimally in carrying out his vital functions. The final chapter deals with the implementation of a research plan relevant to understanding the primary mechanisms of the aging process. This book is a valuable resource for gerontologists, biologists, and molecular biologists.
This book covers the origins and subsequent history of research results in which attempts have been made to clarify issues related to cellular ageing, senescence, and age-related pathologies including cancer. Cellular Ageing and Replicative Senescence revisits more than fifty-five years of research based on the discovery that cultured normal cells are mortal and the interpretation that this phenomenon is associated with the origins of ageing. The mortality of normal cells and the immortality of cancer cells were also reported to have in vivo counterparts. Thus began the field of cytogerontology. Cellular Ageing and Replicative Senescence is organized into five sections: history and origins; serial passaging and progressive ageing; cell cycle arrest and senescence; system modulation; and recapitulation and future expectations. These issues are discussed by leading thinkers and researchers in biogerontology and cytogerontology. This collection of articles provides state-of-the-art information, and will encourage students, teachers, health care professionals and others interested in the biology of ageing to explore the fascinating and challenging question of why and how our cells age, and what can and cannot be done about it.
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.
Americans are living longer, and the elder population is growing larger. To meet the ongoing need for quality information on elder health, the Encyclopedia of Aging and Public Health combines multiple perspectives to offer readers a more accurate and complete picture of the aging process. The book takes a biopsychosocial approach to the complexities of its subject. In-depth introductory chapters include coverage on a historical and demographic overview of aging in America, a guide to biological changes accompanying aging, an analysis of the diversity of the U.S. elder population, legal issues commonly affecting older adults, and the ethics of using cognitively impaired elders in research. From there, over 425 entries cover the gamut of topics, trends, diseases, and phenomena: -Specific populations, including ethnic minorities, custodial grandparents, and centenarians -Core medical conditions associated with aging, from cardiac and pulmonary diseases to Parkinson’s and Alzheimer’s -Mental and emotional disorders -Drugs/vitamins/alternative medicine -Disorders of the eyes, feet, and skin -Insomnia and sleep disorders; malnutrition and eating disorders -Sexual and gender-related concerns -And a broad array of social and political issues, including access to care, abuse/neglect, veterans’ affairs, and assisted suicide Entries on not-quite-elders’ concerns (e.g., midlife crisis, menopause) are featured as well. And all chapters and entries include references and resource lists. The Encyclopedia has been developed for maximum utility to clinicians, social workers, researchers, and public health professionals working with older adults. Its multidisciplinary coverage and scope of topics make this volume an invaluable reference for academic and public libraries.
Forward genetic screens identifying long-lived mutants catalyzed a revolution in aging research. A decade later a second wave of research, spurred by the methodological development of unbiased genome-scale RNAi screens, pushed beyond the identification of individual longevity genes and began to describe genetic and molecular pathways that regulate aging. The discovery of CRISPR-Cas9 technology and its application in genetic screening has just begun to further advance the aging field. An evolving therapeutic strategy for age-related disease involves the selective ablation, using small molecule "senolytics", of senescent cells, which accumulate both with age and in certain pathologies. While a promising therapeutic approach, current senolytic agents are limited to local administration due to their side effects and potency. Genetic CRISPR screens could be applied to senescent cells and help identify improved senolytics, however current screening methodology is not optimized for studying genes which regulate cell death or for non-dividing cell types. Forward genetic screens have not been widely implemented for non-dividing, primary, post-mitotic, or quiescent cell types as many forward genetic screens often require cell sorting or growth-based phenotypes, both of which could be impossible in many cell types. Furthermore, millions of cells are required for sufficient coverage in traditional screens and this scale of experiment is prohibitively expensive and challenging with many specialized cell types. Here, I present new technology to improve the ability of genetic screening to study cell death and bring the power of CRISPR screening to disease-relevant cell types. This technique enables discovery of the molecular mechanisms of cell death subroutines with enhanced signal-to-noise ratios and could help identify drug targets for varied pathological states, such as cancer and neurodegeneration. I have applied this technology in the context of cellular senescence to discover genetic modifiers of senolytics, demonstrate a combination of senolytic drug targets which act synergistically, and provide proof-of-concept that this synergistic senolytic drug combination clears senescent cells in vivo to ameliorate age-related pathology. Chapter 2 introduces this optimized genetic screening methodology, termed "Death-seq", for modifiers of cell death and applies it in a genome-wide screen studying the senolytic agent ABT-263. Chapter 3 demonstrates the ability of Death-seq to find senolytic modifiers with other drugs beyond ABT-263, including drugs which induce negligible cell death on their own, to demonstrate the importance of the drug target SMAC. Chapter 4 details the fact that the BH3 mimetics ABT-263 and ABT-199 act synergistically with SMAC mimetics to selectively ablate senescent cells. Chapter 5 demonstrates that the combination of ABT-199 and the SMAC mimetic birinapant enables the clearance of senescent cells in vivo in mice systemically and ameliorates aspects of certain models of age-related pathology. Overall, these chapters demonstrate the ability of the new genetic screening methodology, Death-seq, to identify modifiers of cell death and show proof-of-concept for this method's ability to discover novel approaches in the context of cellular senescence with therapeutic potential for age-related disease.
As the global population lives to an increasing older age, there is a need to research, develop and deliver appropriate anaesthesia and pain management care to these increasingly frail and vulnerable patients. This book provides a comprehensive and detailed overview of all aspects of anaesthesia for the elderly patient looking at the effect of ageing on the systems of the body and the role that age has on drug mechanisms. Designed for both consultants and traineeswho care for elderly patients, chapters address the clinical management of the older patient in pain, trauma, intensive care as well as anaesthesia for all aspects of surgery. The expert author team use their experience to provide a practical and stimulating book which informs everyday clinical activity and explores the unanswered questions which face anaesthetists in this changing patient population. This book will give all consultants and trainees a thorough grounding in this growing and demanding area of anaesthetic practice.
Aging represents a physiological and per se non-pathological and multifactorial process involving a set of key genes and mechanisms being triggered by different endogenous and exogenous factors. Since aging is a major risk factor in connection with a variety of human disorders, it is increasingly becoming a central topic in biochemical and medical research. The plethora of theories on aging – some of which have been discussed for decades – are neither isolated nor contradictory but instead can be connected in a network of pathways and processes at the cellular and molecular levels. This book summarizes the most prominent and important approaches, focusing on telomeres, DNA damage and oxidative stress as well as on the possible role of nutrition, the interplay between genes and environment (epigenetics) and intracellular protein homeostasis and introduces some genes that have actually extended life spans in animal models. Linking these different determinants of aging with disease, this volume aims to reveal their multiple interdependencies. We see that there is no single “perfect” theory of aging and that instead it is possible to define what the authors call the molecular aging matrix of the cell. A better knowledge of its key mechanisms and the mutual connections between its components will lead to a better understanding of age-associated disorders such as Alzheimer’s disease.