Cellular Senescence In Health Disease And Aging Blessing Or Curse

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.

Social and environmental factors have profound impacts on health and diseases across the lifespan. Each year, hundreds of millions of animals are used in biomedical research. Yet many experimental studies utilize animals housed in standard conditions conferring minimal physical, social, and mental stimulation. Lacking appreciation of macroenvironment impacts on physiology and disease risks of the laboratory animals may not only hinder the use of appropriate animal models for human diseases, but also question the validity of preclinical assessments of therapeutic agents.This book summarizes our work on environmental enrichment, a housing condition for laboratory animals, recapitulating an active lifestyle by providing a complex physical, social, and cognitive stimulations. Environmental enrichment exerts a wide range of benefits on energy balance, cancer, immunity, stress, behavior, and healthy aging. One underlying mechanism is the activation of a specific neuroendocrine brain-adipocyte axis with brain-derived neurotrophic factor as the key brain mediator. This book integrates recent discoveries regarding mechanisms, mediators, and biomarkers of environmental enrichment, and discusses its translational potential.By providing a timely review and discussion of murine models, this book should be of interest to basic, translational, and clinical researchers, as well as psychologists, nutrition scientists, and students that have interest in cancer, obesity, aging, and genetic disorders.

WELCOME TO THE WORLD OF LONGEVITYThe world today is fast progressing and we live in the unprecedented times. There is a boom of advances in every field, from the art to the science and technology. This includes health science, too. The wonderful advances in the field of medical science make it possible to cure acute disorders and, thus, avoiding untimely demise. The chronic diseases like obesity, diabetes, high blood pressure, heart disease, etc. can be efficiently managed leading to virtual freedom from their complications. There is, in general, an appreciable increase in life expectancy and lifespan. The ideology apart, health is the prime instrument that lets us enjoy life. The preservation of health is the best formula for longevity. A healthy food, adequate physical activity and wholesome lifestyle keep the daily attrition-related damage at minimum and retard ageing. An optimal healthcare adds further. An individual's life course may appear unpredictable, but it is not. The genetic and environmental factors, both being of equal importance, and behavioral patterns can successfully predict the life expectancy. The longer life is not separate from ageing slowly. They are mutually related.The life is an eternal truth. We are because we live. We find people ageing; we ourselves age and grow older. The phenomenon of ageing is universal in the kingdom of living. With time, all living beings age. Yet, ageing is an enigma. We do not understand it. We do not exactly know, what makes us age and grow old, finally losing vitality of life? Living a healthy and long life is a common dream. All of us nourish the dream; all of us wish to realize it. But various disorders and infirmities annihilate the dream. Falling prey to them, we lose our health and fitness, and pass through an abridged life. There have been immense developments in scientific research, including medical science. There has evolved a whole novel understanding of the biology of ageing. A vast body of knowledge can explain the changes that take place with ageing at molecular and cellular level. At the same time, the progress in healthcare and technology makes it possible to slow ageing. The science has progressed and there are futuristic visions of achieving significant longevity. There are possibilities of being able to reverse the ageing process. The eternal dream of immortality, is on the verge of becoming a reality. This book aims to provide answers to the questions related to ageing. It aims to explain ageing and charts out a program for slowing ageing. It also gives a peep into the futuristic visions of longevity and suggests scientific ways for a long life. Simultaneously, it is designed to educate you for fitness and to lead a healthy life. As you read through the book, you will find long-held views interspersed with shattering myths, and scientific facts intermingled with results from research and studies, which are still not out of the lab doors. It may seem at times, but the book is not a fiction. Neither, it is a concocted dream. The book is based on current state of scientific knowledge and gerontological research. I intend to share with you the current state of knowledge relating to ageing and gerontology. There are, to share with you, the facts and visions more eloquent than imaginations, and amazing thoughts amounting to the reality-pregnant-early-morning dreams. You will notice few things as you read through the book. Using certain words has been avoided. You will only rarely find the words like aged, old, etc. The words like elderly have been used very sparingly. This has been done purposely and is well in line with the central thought of the book, which is to come out of our age-old prejudices against the old age. So, I request you to read on. After all, theme of the book ageing slowly and living longer, as indicated by the title chosen, is of the prime concern to all of us. Your partner in healthy long life, Dr Vinod Nikhra, M.D.

Homeostasis involves a delicate interplay between generative and degenerative processes to maintain a stable internal environment. In biological systems, equilibrium is established and controlled through a series of negative feedback mechanisms driven by a range of signal transduction processes. Failures in these complex communication pathways result in instability leading to disease. Cancer represents a state of imbalance caused by an excess of cell proliferation. In contrast, neurodegeneration is a consequence of excessive cell loss in the nervous system. Both of these disorders exhort profound tolls on humanity and they have been subject to a great deal of research designed to ameliorate this suffering. For the most part, the topics have been viewed as distinct and rarely do opportunities arise for transdisciplinary discussions among experts in both fields. However, cancer and neurodegeneration represent yin-yang counterpoints in the regulation of cell growth, and it is reasonable to hypothesize that key regulatory events mediated by oncogenes and tumor suppressor genes in cancer may also affect neurodegenerative processes

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.

A palliative care doctor on the front lines of hospital care illuminates one of the most important and controversial ethical issues of our time on his quest to transform care through the end of life. It is harder to die in this country than ever before. Statistics show that the vast majority of Americans would prefer to die at home, yet many of us spend our last days fearful and in pain in a healthcare system ruled by high-tech procedures and a philosophy to "fight disease and illness at all cost." Dr. Ira Byock, one of the foremost palliative-care physicians in the country, argues that end-of-life care is among the biggest national crises facing us today. In addressing the crisis, politics has trumped reason. Dr. Byock explains that to ensure the best possible care for those we love-and eventually ourselves- we must not only remake our healthcare system, we must also move past our cultural aversion to talking about death and acknowledge the fact of mortality once and for all. Dr. Byock describes what palliative care really is, and-with a doctor's compassion and insight-puts a human face on the issues by telling richly moving, heart-wrenching, and uplifting stories of real people during the most difficult moments in their lives. Byock takes us inside his busy, cutting-edge academic medical center to show what the best care at the end of life can look like and how doctors and nurses can profoundly shape the way families experience loss. Like books by Atul Gawande and Jerome Groopman, The Best Care Possible is a compelling meditation on medicine and ethics told through page-turning, life or death medical drama. It is passionate and timely, and it has the power to lead a new kind of national conversation.

From the opening sequence, in which mid-nineteenth-century Indian fishermen hear the possibility of redemption in an old woman's madness, No Aging in India captures the reader with its interplay of story and analysis. Drawing on more than a decade of ethnographic work, Lawrence Cohen links a detailed investigation of mind and body in old age in four neighborhoods of the Indian city of Varanasi (Banaras) with events and processes around India and around the world. This compelling exploration of senility—encompassing not only the aging body but also larger cultural anxieties—combines insights from medical anthropology, psychoanalysis, and postcolonial studies. Bridging literary genres as well as geographic spaces, Cohen responds to what he sees as the impoverishment of both North American and Indian gerontologies—the one mired in ambivalence toward demented old bodies, the other insistent on a dubious morality tale of modern families breaking up and abandoning their elderly. He shifts our attention irresistibly toward how old age comes to matter in the constitution of societies and their narratives of identity and history.