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This book is devoted to innovative medicine, comprising the proceedings of the Uehara Memorial Foundation Symposium 2014. It remains extremely rare for the findings of basic research to be developed into clinical applications, and it takes a long time for the process to be achieved. The task of advancing the development of basic research into clinical reality lies with translational science, yet the field seems to struggle to find a way to move forward. To create innovative medical technology, many steps need to be taken: development and analysis of optimal animal models of human diseases, elucidation of genomic and epidemiological data, and establishment of “proof of concept”. There is also considerable demand for progress in drug research, new surgical procedures, and new clinical devices and equipment. While the original research target may be rare diseases, it is also important to apply those findings more broadly to common diseases. The book covers a wide range of topics and is organized into three complementary parts. The first part is basic research for innovative medicine, the second is translational research for innovative medicine, and the third is new technology for innovative medicine. This book helps to understand innovative medicine and to make progress in its realization.
This book offers comprehensive information on the new and rapidly evolving science of identifying and targeting senescent cells, and on the exciting prospect of new diagnostic and therapeutic opportunities for stopping, and even reversing, the progression of disease and the deterioration of the human body due to ageing. According to recent United Nations data, by 2050 one in six people worldwide will be older than age 65, with peaks rising to one in four people in Europe and North America. Remarkably, the number of persons aged 80 years or older is expected to triple, from 143 million in 2019 to 426 million in 2050. First documented in the 1960s, the concept of cellular senescence as an underlying cause of ageing has been established in the course of the last decade. Using genetically engineered mouse models, researchers have demonstrated that the selective elimination of senescent cells can block and even reverse a number of age-related dysfunctions and pathologies, promoting both better health and longer life in the elderly. These include cardiovascular diseases; neurological disorders; type 1 and type 2 diabetes; inflammatory diseases; fibrosis; geriatric syndromes; chronic diseases resulting in organ dysfunction; the integrity of the musculoskeletal system; and cancer. Some senolytic agents have already progressed into trials. These include UBX0101 for the treatment of osteoarthritis (now in phase II), a cocktail of dasatinib and quercetin for the management of idiopathic pulmonary fibrosis and chronic kidney disease, and ABT-263 in combination with senescence-inducing chemotherapies for the treatment of advanced solid tumours. In addition, the book discusses pathways to early phase clinical trials and translational approaches in medicine and ageing, highlighting new opportunities as well as current limitations, challenges and alternatives. Given its scope, it will benefit a broad audience of advanced educators, researchers, graduate students and practitioners.
The Biology of Senescence
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 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 inspired a large number of theories trying to rationalize the aging process common to all living beings. In this publication the most important environmental and intrinsic mechanisms involved in the aging process and in its pathological consequences are reviewed. Furthermore theoretical and experimental evidence of the most important theoretical elements based on Darwinian evolution, cellular aging, role of cell membranes, free radicals and oxidative processes, receptor-mediated reactions, the extracellular matrix and immune functions as well as the most important environmental and intrinsic mechanisms involved in the aging process and in its pathological consequences are discussed. These presentations of theories and related experimental facts give a global overview of up to date concepts of the biology of the aging process and are of essential reading not only for specialists in this field but also for practitioners of scientific, medical, social and experimental sciences.
This book investigates the various processes that are affected by the age of an organism. Several new tools for the analysis of biological aging have been introduced recently, and this volume provides methods and protocols for these new techniques in addition to its coverage of established procedures. Researchers seeking new technology and techniques will find this volume of tremendous benefit as they move towards new directions.
This book equips dental care providers with a thorough understanding of the emerging therapies that promise to revolutionize the clinical management of periodontal diseases. Existing therapies targeted to the oral microbiome alone often fail to provide favorable clinical outcomes. Local inflammation and tissue destruction may persist and periodontal tissue regeneration is not predictably achieved. In recognition of these shortcomings, current research efforts are focused on understanding the biological interactions between the host and the resident microbiome and identifying key molecules and molecular pathways that can be used for more targeted, individualized therapies that will restrain oral inflammation and restore periodontal tissue homeostasis. This book introduces novel concepts and molecules that are currently being tested in preclinical and clinical models. Readers will find detailed information from leading experts on specific therapeutic strategies targeting the host immune and inflammatory system, the oral microbiome, and regeneration.
The purpose of this book is to provide information on senescent cells and why they are prevented from multiplying via cell division. It includes main sections on the nature of Go/1 transition, factors promoting the cell cycle traverse and avoiding the Go/1 arrest, and negative factors arresting the cell cycle traverse and promoting the stay in the Go/1 stage. Filled with illustrations and explanations, it collectively presents the mechanisms that control the cellular aging process. This reference is a must for anyone with special interests in the biological community, and specifically the field of gerontology.
Molecular Aspects of Aging: Understanding Lung Aging covers recent research in the mechanisms that contribute to cellular senescence. Covering universal themes in aging, such as the exhaustion of stem cells and subsequent loss of the regenerative refueling of organs as well as immunosenescence, this text illuminates new directions for research not yet explored in the still poorly investigated area of molecular mechanisms of lung aging. The molecular nature of general aging processes is explored with targeted coverage on how to analyze lung aging through experimental approaches.