Subcellular Biochemistry 91 J. Robin Harris Viktor I. Korolchuk Editors Biochemistry and Cell Biology of Ageing: Part II Clinical Science Subcellular Biochemistry Volume 91 Series editor J. Robin Harris, Institute of Zoology, University of Mainz, Mainz, Germany More information about this series at http://www.springer.com/series/6515 J. Robin Harris • Viktor I. Korolchuk Editors Biochemistry and Cell Biology of Ageing: Part II Clinical Science Editors J. Robin Harris Viktor I. Korolchuk Institute of Zoology Newcastle University University of Mainz Newcastle upon Tyne, UK Mainz, Germany ISSN 0306-0225 Subcellular Biochemistry ISBN 978-981-13-3680-5 ISBN 978-981-13-3681-2 (eBook) https://doi.org/10.1007/978-981-13-3681-2 Library of Congress Control Number: 2018965214 © Springer Nature Singapore Pte Ltd. 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, express or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Singapore Pte Ltd. The registered company address is: 152 Beach Road, #21-01/04 Gateway East, Singapore 189721, Singapore Foreword Never has it been more important or timely for new volumes on the science of age- ing to be produced. Around the world, continuing gains in life expectancy coupled with declining fertility rates in many countries are producing profound shifts in demographic profiles. A growing fraction of the population is living to advanced old age, bringing with it increased prevalence of a wide range of age-related chronic diseases. Whereas it was once thought that ageing was something that just happened and that was relatively low on the priority list for research, recent decades have seen exciting advances in probing the complex mechanisms through which the ageing process develops. We have come a long way from the days when it was simply assumed there was some internal biological clock that would allow us an allotted span of “three score years and ten” and then kill us. Few had questioned why ageing should impose this fate upon us. It was loosely supposed that it was nature’s way of creating living space for the next generation and securing evolutionary succession. We now know that these old-fashioned concepts have little credence. During our evolution, our genomes evolved impressive systems to try and preserve functional homeostasis in the biochemistry and cell biology of our bodies. The trouble is that there was never the evolutionary pressure to make these systems good enough completely to prevent damage from accumulating. Gradually, and at first unobtrusively, things begin to go wrong, starting from the earliest stages of life. And it is not one thing above all oth- ers – many systems experience deterioration at the same time. Herein lies the intriguing challenge of trying to unpick the contributions of the individual mecha- nisms that are being found to play their part in ageing and then of putting it all together. Understanding the biochemistry of ageing is among the most complex of prob- lems in the life sciences. On the one hand, we need to be intensively reductionist. We need to identify the fine detail of each one of the many biochemical mechanisms that contribute to functional decline. On the other hand, we need to appreciate that knowing everything there is to know about one particular mechanism may tell us rather little about the ageing process itself. To get the bigger picture, we must acknowledge that it makes little sense to argue the case for this mechanism versus v vi Foreword that mechanism and so on. It is not a matter of simple alternatives. Instead of rooting for mechanism A or B or … or Z, we must learn to appreciate that it is A and B and … and Z. Whether we call this integrative biology, or systems biology, or some other term of a similar nature, the bottom line is that we need to join forces and learn as much as we can about the different biochemical mechanisms and their often syn- ergistic interactions. In some ways, the science of ageing is the science of life itself. In the traditional school of biochemistry, we learn about how life has evolved the remarkable processes of DNA replication, transcription, translation, turnover, signal transduction, cell division and all the rest. These systems are so beautifully coordi- nated that we might marvel at first at how well they work. But the underlying molec- ular interactions are noisy and subject to perturbations of all kinds and at all times. It is this reverse side of the orderliness of biochemical processes that we need to appreciate to understand ageing. In clinical terms, ageing is equally complex and challenging. Age is much the largest risk factor for a whole spectrum of different diseases, dwarfing the contribu- tions from genetic, lifestyle and environmental risk factors. Furthermore, the fact that so many conditions share ageing as their dominant risk factor means it is no surprise that very old people commonly exhibit extensive multi-morbidity. But is ageing normal, or is it a disease? The answer is that ageing is a normal biological process, but it has the distinctive property that it makes us more vulnerable to dis- eases of many kinds. So it is a bit of a hybrid – both normal and also the source of pathologies. The old arguments about whether ageing is normal or disease are not particularly helpful. Ageing is driven by the accumulation of damage in our cells and organs, and the same is true of age-related, chronic diseases. Thus, there is a huge overlap. Once we understand the basic mechanisms of ageing itself, we will gain valuable knowledge about the many diseases which may affect us in later life. Thus, the study of the biochemistry and cell biology of ageing should seek to com- bine biomedical and clinical science. It is to be warmly welcomed, therefore, that J. Robin Harris and Viktor Korolchuk have produced these twin volumes, bringing into intimate juxtaposition a collection of state-of-the-art reviews of the biochemis- try of ageing from both perspectives. Emeritus Professor Thomas B. L. Kirkwood Newcastle University Institute for Ageing, Campus for Ageing and Vitality, Newcastle upon Tyne, UK Preface This book, Biochemistry and Cell Biology of Ageing: Part II, Clinical Science (along with Part I, Biomedical Science) was conceived following the reading (by JRH) of Lewis Wolpert’s controversial yet thoroughly enjoyable 2011 book You’re Looking Very Well: The Surprising Nature of Getting Old. As a broad discipline, ageing has been deemed to fit in well with the diverse content of the Springer Subcellular Biochemistry series; the two books covering biomedical science and clinical science were duly commissioned by the Springer Company. We have attempted to compile a list of chapters written by authoritative clinical scientists to cover the field as thoroughly as possible. Along the way to production, a few chapters failed to appear! Nevertheless, the remaining 17 chapters provide a good coverage of the subject. To place the available chapters in a logical sequence has defeated us; we have simply presented them here as they appear in our initial list of agreed chapters, at the time of compilation. Each clinical science chapter stands firmly on its own merit, with correlation to the Biological Science book chapters in some cases. Over recent decades, ageing research has expanded enormously world- wide, responding to the increased importance to and interest from the general popu- lation, where there is an obvious desire to retain “quality of life”, health and self-sufficiency into the later years. The Contents list page, immediately following this Preface, shows the range of topics that are included. Without singling out any individual topic and author(s), it is clear that most of the important aspects of ageing research are included. Together they provide an in-depth survey of numerous aspects within the field of ageing research with clinical emphasis. We hope that the book will be of value to under- graduate biomedical science students, medical students, postgraduate researchers, clinicians and academics involved and interested in aspects of ageing research. Mainz, Germany J. Robin Harris Newcastle upon Tyne, UK Viktor I. Korolchuk August, 2018 vii Contents 1 Poor Early Growth and Age-Associated Disease.................................. 1 Jane L. Tarry-Adkins and Susan E. Ozanne 2 The Immune System and Its Dysregulation with Aging ...................... 21 Ludmila Müller, Svetlana Di Benedetto, and Graham Pawelec 3 Pulmonary Diseases and Ageing ............................................................ 45 Peter J. Barnes 4 Neurodegenerative Diseases and Ageing ............................................... 75 Lauren Walker, Kirsty E. McAleese, Daniel Erskine, and Johannes Attems 5 Ageing and Cognition ............................................................................. 107 Sydney M. A. Juan and Paul A. Adlard 6 Ageing and Osteoarthritis ...................................................................... 123 Pradeep Kumar Sacitharan 7 Down Syndrome, Ageing and Epigenetics ............................................ 161 Noémie Gensous, Claudio Franceschi, Stefano Salvioli, Paolo Garagnani, and Maria Giulia Bacalini 8 The Vestibular System and Ageing ........................................................ 195 Sonja Brosel and Michael Strupp 9 Signal Transduction, Ageing and Disease ............................................. 227 Lei Zhang, Matthew J. Yousefzadeh, Yousin Suh, Laura J. Niedernhofer, and Paul D. Robbins 10 Skin Changes During Ageing ................................................................. 249 Frédéric Bonté, Dorothée Girard, Jean-Christophe Archambault, and Alexis Desmoulière 11 Connective Tissue and Age-Related Diseases ....................................... 281 Carolyn Ann Sarbacher and Jaroslava T. Halper ix x Contents 12 Potential Cellular and Biochemical Mechanisms of Exercise and Physical Activity on the Ageing Process ........................................ 311 Mark Ross, Hannah Lithgow, Lawrence Hayes, and Geraint Florida-James 13 Health Benefits of Anti-aging Drugs...................................................... 339 Veronika Piskovatska, Olha Strilbytska, Alexander Koliada, Alexander Vaiserman, and Oleh Lushchak 14 Visual Defects and Ageing ...................................................................... 393 Sergio Claudio Saccà, Carlo Alberto Cutolo, and Tommaso Rossi 15 Hutchinson-Gilford Progeria Syndrome: Challenges at Bench and Bedside .............................................................................. 435 Ray Kreienkamp and Susana Gonzalo 16 Osteoporosis and the Ageing Skeleton .................................................. 453 Terry J. Aspray and Tom R. Hill 17 Neurovascular Ageing and Age-Related Diseases ................................ 477 Raj N. Kalaria and Yoshiki Hase
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