Cellular Senescence In Disease

Winner of the 2023 PROSE award in Biomedicine and Neuroscience! Research in the field of senescence has boomed recently due to the gradual realization that senescent cells are associated with a significant number of diseases. The genetic or pharmacological elimination of senescent cells can cause widespread benefits and improves outcomes for most of those diseases. Cellular Senescence in Diseases presents an updated review of the role of cellular senescence in multiple pathologies. Focus is given to those diseases where the implication of senescence has been more extensively documented, such as (cancer, lung and liver diseases, diabetes, Neurodegenerative diseases and others). The Editors recruited a group of worldwide experts in each individual pathology to review the role of cellular senescence in each one of them, aiming at identifying potential therapeutic pathways. The first two chapters provide an overview of the cellular senescence principles. Next, the chapters are divided into specific diseases. Cancer, including premalignant lesions (OIS), Advanced disease (TIS), and Metastasis are covered. The following condition covered is Lund diseases, including IPF, COPD, and Pulmonary Hypertension. Next Liver Diseases are covered, including Fibrosis and Cirrhosis, and Fatty liver disease. Next there is coverage for Kidney implications, including fibrosis and transplantation. Vascular diseases are covered next including infarction and hear fibrosis, and atherosclerosis. Both diabetes types 1 and 2 are covered next. Following chapters cover Obesity, Sarcopenia, and Bone and Cartilage disorders, respectively. Neurodegenerative diseases are covered next, focusing on Alzheimer and Parkinson. The next chapter discusses accumulation of senescent cell in tissues during aging. The two final chapters cover current developments and conclusions. Cellular Senescence in Diseases is designed for researchers and clinicians with a focus on the cellular mechanisms of diseases. All chapters cover current experimental therapeutic approaches to eliminate or cancel the pathological effects of senescent cells. Pharmaceutical scientists may also benefit from the contents of the book in the exploration of novel therapeutic opportunities. 2023 PROSE Awards - Winner: Category: Biomedicine and Neuroscience: Association of American Publishers Provides a thorough introduction to Cellular Senescence Covers all major pathologies for which cellular senescence has shown evidence of involvement Focuses on possible therapeutic pathways Edited and authored by worldwide experts

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 demographic shift in the average age of the population worldwide calls for careful attention to the nutritional and health needs of the elderly. Frailty has been associated with increased disability, postsurgical complications and increased mortality; in a frail state, older adults are at greater risk for adverse outcomes, including falls and admissions to hospital and nursing homes. Despite the strong associations between frailty and subsequent poor outcomes, limited attention to this common geriatric condition has been paid in clinical settings. Emerging evidence suggests that both behavioral (nutrition and physical activity) and pharmacologic interventions may be effective in the treatment and prevention of the frailty syndrome. The papers in this book address our current understanding of the biological basis, clinical presentation and therapeutic interventions that target frailty. They highlight the transitional nature of research on the frailty syndrome and identified key unmet needs and areas for future investigation in this expanding field.

Despite decades of attention on building a global HIV research and programming agenda, HIV in older populations has generally been neglected until recently. This new book focuses on HIV and aging in the context of ageism with regard to prevention, treatment guidelines, funding, and the engagement of communities and health and social service organizations. The lack of perceived HIV risk in late adulthood among older people themselves, as well on the part of providers and society in general, has led to a lack of investment in education, testing, and programmatic responses. Ageism perpetuates the invisibility of older adults and, in turn, renders current medical and social service systems unprepared to respond to patients’ needs. While ageism may lead to some advantages – discounts for services, for example – it is the negative aspects that must be addressed when determining the appropriate community-level response to the epidemic.

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.

This book aims to clarify the potential association between frailty and cardiovascular disease in older people. Covering the biological as well as the clinical point of view, it allows researchers and clinicians to discover the significance of this topic. The contributions cover the most important aspects in the potential relationship between frailty and cardiovascular disease. In particular, authoritative authors in this field have clarified the definition and the epidemiology of frailty and cardiovascular disease in older people. A large part of the volume is dedicated to the biological mechanisms of frailty and cardiovascular disease, trying to find those in common between these two conditions. Since this book is dedicated to both researchers and clinicians, we have proposed some chapters to the importance of comprehensive geriatric assessment in the evaluation and treatment of cardiovascular diseases and frailty. In this regard, the importance of geriatric evaluation in cardiac surgery for older people is well covered. Finally, the importance of cardiac rehabilitation and physical exercise is summarized, being, actually, the most important treatments for both frailty and cardiovascular disease. Written by many well-known and widely published experts in their respective fields, this book will appeal to a wide readership such as researchers in the field and clinicians, especially suited in geriatric medicine and cardiology who, every day, face frail older patients.

Dear Colleagues, When Hayflick and Moorhead coined the term “cellular senescence” (CS) almost 60 years ago, this phenomenon was understood as a mechanism, usually induced by activation of the DNA-repair machinery, to prevent uncontrolled proliferation. Meanwhile, additional beneficial roles for CS have been identified, such as embryonic development and wound healing. The senescence associated secretory phenotype (SASP) activated in most senescent cells (SC) signals to the immune system “come here and remove me”. In organisms with young and functional immune systems, occurring SC are usually detected and removed. If SC remain in the tissue expressing the SASP, this will cause not just a damaging local inflammation but can also induce remodeling and regeneration of the surrounding tissue as well as spreading of senescence. Old organisms show reduced regenerative potential and immune function which leads to accumulation of SC. Accordingly, accumulation of SC was observed in tissues of aged individuals, but importantly also in the context of age-related disorders, neurodegenerative, or cardiovascular diseases and others. Because of its detrimental effect of the surrounding tissue, accumulation of SC is not just a consequence, but can rather been understood as a major driver of aging. In line with this, recent studies described that removal of SC showed beneficial effects on healthspan and lifespan. This exciting research led to the discovery of “senolytics”, drugs which can kill SC. Given the heterogeneity of cell types that show senescence-like phenotypes, including heart muscle and post-mitotic neuronal cells, further research is required to unravel the molecular background that renders a cell type vulnerable to senesce. Additionally, it will be important to understand how senescence is cell type-specifically induced and which molecules serve as drug targets to prevent senescence and its spreading, or actively kill SC. This special issue will shed light on the molecular pathways of CS and inflammaging and on possible strategies to interfere with these processes. Dr. Markus Riessland Guest Editor.