Download or read book Dissecting Cell Death Cellular Senescence and Aging with Genetic Screens written by Alexander James Colville and published by . This book was released on 2021 with total page pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Plant Cell Death Processes written by Larry D. Nooden and published by Elsevier. This book was released on 2003-12-09 with total page 419 pages. Available in PDF, EPUB and Kindle. Book excerpt: Programmed cell death is a common pattern of growth and development in both animals and plants. However, programmed cell death and related processes are not as generally recognized as central to plant growth. This is changing fast and is becoming more of a focus of intensive research. This edited work will bring under one cover recent reviews of programmed cell death, apoptosis and senescence. Summaries of the myriad aspects of cell death in plants Discussion of the broadest implications of these disparite results A unification of fields where there has been no cross talk Enables easy entry into diverse but related lines of research
Download or read book Mechanisms of Cell Death written by Zahra Zakeri and published by . This book was released on 1999 with total page 236 pages. Available in PDF, EPUB and Kindle. Book excerpt: Contains papers from a July 1998 conference held at the Queens College Campus of the City University of New York. Papers are arranged in sections on mechanisms and general considerations, programmed (developmental) cell death, and cell death and pathological and clinical situations. Specific topics
Download or read book Senolytics in Disease Ageing and Longevity written by Daniel Muñoz-Espin and published by Springer Nature. This book was released on 2020-04-27 with total page 226 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Between Zeus and the Salmon written by Caleb E. Finch and published by . This book was released on 1997-10-29 with total page 304 pages. Available in PDF, EPUB and Kindle. Book excerpt: Demographers and public health specialists have been surprised by the rapid increases in life expectancy, especially at the oldest ages, that have occurred since the early 1960s. Some scientists are calling into question the idea of a fixed upper limit for the human life span. There is new evidence about the genetic bases for both humans and other species. There are also new theories and models of the role of mutations accumulating over the life span and the possible evolutionary advantages of survival after the reproductive years. This volume deals with such diverse topics as the role of the elderly in other species and among human societies past and present, the contribution of evolutionary theory to our understanding of human longevity and intergenerational transfers, mathematical models for survival, and the potential for collecting genetic material in household surveys. It will be particularly valuable for promoting communication between the social and life sciences.
Download or read book Chlorophyll a Fluorescence written by G.C. Papageorgiou and published by Springer Science & Business Media. This book was released on 2007-11-12 with total page 853 pages. Available in PDF, EPUB and Kindle. Book excerpt: Chlorophyll a Fluorescence: A Signature of Photosynthesis highlights chlorophyll (Chl) a fluorescence as a convenient, non-invasive, highly sensitive, rapid and quantitative probe of oxygenic photosynthesis. Thirty-one chapters, authored by 58 international experts, provide a solid foundation of the basic theory, as well as of the application of the rich information contained in the Chl a fluorescence signal as it relates to photosynthesis and plant productivity. Although the primary photochemical reactions of photosynthesis are highly efficient, a small fraction of absorbed photons escapes as Chl fluorescence, and this fraction varies with metabolic state, providing a basis for monitoring quantitatively various processes of photosynthesis. The book explains the mechanisms with which plants defend themselves against environmental stresses (excessive light, extreme temperatures, drought, hyper-osmolarity, heavy metals and UV). It also includes discussion on fluorescence imaging of leaves and cells and the remote sensing of Chl fluorescence from terrestrial, airborne, and satellite bases. The book is intended for use by graduate students, beginning researchers and advanced undergraduates in the areas of integrative plant biology, cellular and molecular biology, plant biology, biochemistry, biophysics, plant physiology, global ecology and agriculture.
Download or read book Cell Senescence written by Lorenzo Galluzzi and published by Humana Press. This book was released on 2013-01-08 with total page 0 pages. Available in PDF, EPUB and Kindle. Book excerpt: Cell senescence is the process whereby cells permanently lose the possibility to proliferate without undergoing cell death, and occurs in a plethora of distinct model organisms. In Cell Senescence: Methods and Protocols, expert researchers in the field detail the methods that are now commonly used to study cell senescence, in model organisms encompassing bacteria, fungi, worms, flies, zebrafish, and mammalian cells. These techniques cover the study of all the morphological, biochemical and functional manifestations of senescence at the cellular level and include protocols for population analyses and high-throughput approaches in suitable model organisms. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.
Download or read book The Functional Nucleus written by David P. Bazett-Jones and published by Springer. This book was released on 2016-10-17 with total page 501 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book gives an in-depth overview on nuclear structure and function. It clearly shows that the epigenome and the three-dimensional organization of the nucleus are not independent properties. The intimate relationship between the location and the epigenetic modifications of gene loci is highlighted. Finally, it shows that the complex three-dimensional organization of the nucleus is not just of academic interest: The structure, composition and function of virtually all of the sub-nuclear compartments identified so far can be implicated to a list of human genetic diseases. Hence, a detailed elucidation of how these domains are assembled and function will provide new opportunities for therapeutic intervention in clinical practice.
Download or read book The Oxford Handbook of Evolutionary Medicine written by Martin Brüne and published by Oxford University Press. This book was released on 2019-01-31 with total page 992 pages. Available in PDF, EPUB and Kindle. Book excerpt: Medicine is grounded in the natural sciences, among which biology stands out with regard to the understanding of human physiology and conditions that cause dysfunction. Ironically though, evolutionary biology is a relatively disregarded field. One reason for this omission is that evolution is deemed a slow process. Indeed, macroanatomical features of our species have changed very little in the last 300,000 years. A more detailed look, however, reveals that novel ecological contingencies, partly in relation to cultural evolution, have brought about subtle changes pertaining to metabolism and immunology, including adaptations to dietary innovations, as well as adaptations to the exposure to novel pathogens. Rapid pathogen evolution and evolution of cancer cells cause major problems for the immune system to find adequate responses. In addition, many adaptations to past ecologies have turned into risk factors for somatic disease and psychological disorder in our modern worlds (i.e. mismatch), among which epidemics of autoimmune diseases, cardiovascular diseases, diabetes and obesity, as well as several forms of cancer stand out. In addition, depression, anxiety and other psychiatric conditions add to the list. The Oxford Handbook of Evolutionary Medicine is a compilation of cutting edge insights into the evolutionary history of ourselves as a species, and how and why our evolved design may convey vulnerability to disease. Written in a classic textbook style emphasising physiology and pathophysiology of all major organ systems, the Oxford Handbook of Evolutionary Medicine will be valuable for students as well as scholars in the fields of medicine, biology, anthropology and psychology.
Download or read book Practical Applications of Chlorophyll Fluorescence in Plant Biology written by Jennifer R. DeEll and published by Springer Science & Business Media. This book was released on 2012-12-06 with total page 271 pages. Available in PDF, EPUB and Kindle. Book excerpt: The technique of chlorophyll fluorescence has a relatively short history, beginning with the observations by Kautsky (Kautsky and Hirsch, 1931). Since that time there have been several· reviews devoted to the subject, with most of them highly theoretical (Bohlar-Nordenkampf and Oquist, 1993; Dau, 1994; Schreiber et aI. , 1994). There have also been many books devoted to generalized spectrophotometric and microscopic fluorescence techniques. However, to the best of our knowledge there has not been a book completely devoted to the practical applications and uses of chlorophyll fluorescence in plant biology. As techniques mature, applications multiply and so do their potential advantages. The chlorophyll fluorescence technique is maturing as can be seen in the increasing numbers of publications that are devoted to its use. Therefore, we considered that now was a good time to compile the existing knowledge for the applied use of this technique and provide a single volume to which a novice or experienced user could refer. Highly trained experts in the field of photobiology have primarily used the chlorophyll fluorescence technique in the past. In that work, understanding the mechanisms and controls of the photosynthetic processes was the main focus of activity and discussion. Much of the equipment used was highly specialized and expensive, or in some cases one-of-a-kind lab designed units. However, the development of several reliable commercially available chlorophyll fluorescence monitoring instruments has changed the potential user base for the technique.
Download or read book Cellular Aging and Cell Death written by Nikki J. Holbrook and published by John Wiley & Sons. This book was released on 1995-12-20 with total page 344 pages. Available in PDF, EPUB and Kindle. Book excerpt: 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.
Download or read book Advances in Mitochondrial Medicine written by Roberto Scatena and published by Springer Science & Business Media. This book was released on 2012-03-08 with total page 459 pages. Available in PDF, EPUB and Kindle. Book excerpt: Mitochondria are far more than the “powerhouse” of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of ‘mitochondrial medicine’, which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.
Download or read book Brain Aging written by David R. Riddle and published by CRC Press. This book was released on 2007-04-19 with total page 408 pages. Available in PDF, EPUB and Kindle. Book excerpt: Recognition that aging is not the accumulation of disease, but rather comprises fundamental biological processes that are amenable to experimental study, is the basis for the recent growth of experimental biogerontology. As increasingly sophisticated studies provide greater understanding of what occurs in the aging brain and how these changes occur
Download or read book Cardiac Regeneration written by Masaki Ieda and published by Springer. This book was released on 2017-10-27 with total page 274 pages. Available in PDF, EPUB and Kindle. Book excerpt: This Volume of the series Cardiac and Vascular Biology offers a comprehensive and exciting, state-of-the-art work on the current options and potentials of cardiac regeneration and repair. Several techniques and approaches have been developed for heart failure repair: direct injection of cells, programming of scar tissue into functional myocardium, and tissue-engineered heart muscle support. The book introduces the rationale for these different approaches in cell-based heart regeneration and discusses the most important considerations for clinical translation. Expert authors discuss when, why, and how heart muscle can be salvaged. The book represents a valuable resource for stem cell researchers, cardiologists, bioengineers, and biomedical scientists studying cardiac function and regeneration.
Download or read book Aging Mechanisms written by Nozomu Mori and published by Springer. This book was released on 2015-11-26 with total page 435 pages. Available in PDF, EPUB and Kindle. Book excerpt: This book brings together the most up-to-date information on recent research results of leading laboratories on aging science in East Asia, particularly in Japan, Korea, and Hong Kong. Starting with a comprehensive overview of various hypotheses on biological mechanisms of aging by Dr. Sataro Goto, each chapter covers broad aspects of the most recent findings in aging-related topics: centenarian studies and genome analysis of progeria, metabolic biochemistry and neurobiology, longevity controls in yeast and nematodes, oxidative stress and calorie restriction, and neurodegeneration mechanisms in Alzheimer’s and Huntington’s diseases, with further potential therapeutic approaches to these age-related neurodegenerative diseases. Also included, in part, is a summary and the outcomes of a scientific discussion forum called the Asian Aging Core for Longevity (AACL) that has been held annually alternating between Japan and Korea during the last decade. This book can serve as a useful resource for finding appropriate collaborators in the areas it covers. The target readership is made up of graduate students and researchers at universities, medical and/or life-science schools, and biomedical and pharmaceutical institutes. Why does aging exist? How do we age? How is each organism’s lifespan determined? These are fundamental questions in the field. We may be still far from achieving a complete view of aging mechanisms, but this book, Aging Mechanisms, offers an excellent opportunity to become familiar with the most updated progress in the biomedical research of aging in Japan and Korea, the two leading nations for human longevity.
Download or read book Microtubule Dynamics written by Anne Straube and published by Humana Press. This book was released on 2017-04-30 with total page 319 pages. Available in PDF, EPUB and Kindle. Book excerpt: Microtubules are at the heart of cellular self-organization, and their dynamic nature allows them to explore the intracellular space and mediate the transport of cargoes from the nucleus to the outer edges of the cell and back. In Microtubule Dynamics: Methods and Protocols, experts in the field provide an up-to-date collection of methods and approaches that are used to investigate microtubule dynamics in vitro and in cells. Beginning with the question of how to analyze microtubule dynamics, the volume continues with detailed descriptions of how to isolate tubulin from different sources and with different posttranslational modifications, methods used to study microtubule dynamics and microtubule interactions in vitro, techniques to investigate the ultrastructure of microtubules and associated proteins, assays to study microtubule nucleation, turnover, and force production in cells, as well as approaches to isolate novel microtubule-associated proteins and their interacting proteins. Written in the highly successful Methods in Molecular BiologyTM series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Definitive and practical, Microtubule Dynamics: Methods and Protocols provides the key protocols needed by novices and experts on how to perform a broad range of well-established and newly-emerging techniques in this vital field.
Download or read book Membrane Biogenesis written by Jos A.F. Op den Kamp and published by Springer Science & Business Media. This book was released on 2013-06-29 with total page 474 pages. Available in PDF, EPUB and Kindle. Book excerpt: Many individual aspects of the dynamics and assembly of biological membranes have been studied in great detail. Cell biological approaches, advanced genetics, biophysics and biochemistry have greatly contributed to an increase in our knowledge in this field.lt is obvious however, that the three major membrane constituents - lipids, proteins and carbohydrates- are studied, in most cases separately and that a coherent overview of the various aspects of membrane biogenesis is not readily available. The NATO Advanced Study Institute on "New Perspectives in the Dynamics of Assembly of Biomembranes" intended to provide such an overview: it was set up to teach students and specialists the achievements obtained in the various research areas and to try and integrate the numerous aspects of membrane assembly into a coherent framework. The articles in here reflect this. Statting with detailed contributions on phospholipid structure, dynamics, organization and biogenesis, an up to date overview of the basic, lipidic backbone of biomembranes is given. Extensive progress is made in the research on membrane protein biosynthesis. In particular the post- and co-translational modification processes of proteins, the mechanisms of protein translocation and the sorting mechanisms which are necessary to direct proteins to their final, intra - or extracellular destination have been characterized in detail. Modern genetic approaches were indispensable in this research area: gene cloning, hybrid protein construction, site directed mutagenesis and sequencing techniques elucidated many functional aspects of specific nucleic acid and amino acid sequences.
