Biochemistry and Cell Biology of Ageing: Part I Biomedical Science

531 Pages·2018·9.9 MB·English

by  J. Robin Harris

Subcellular Biochemistry 90
J. Robin Harris
Viktor I. Korolchuk Editors
Biochemistry
and Cell Biology
of Ageing:
Part I Biomedical
Science
Subcellular Biochemistry
Volume 90
Series editor
J. Robin Harris
Institute of Molecular Physiology, Johannes Gutenberg University,
Mainz, Germany
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Mainz, Germany
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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 I
Biomedical Science
Editors
J. Robin Harris Viktor I. Korolchuk
Institute of Molecular Physiology Newcastle University
Johannes Gutenberg University Newcastle upon Tyne, UK
Mainz, Germany
ISSN 0306-0225
Subcellular Biochemistry
ISBN 978-981-13-2834-3 ISBN 978-981-13-2835-0 (eBook)
https://doi.org/10.1007/978-981-13-2835-0
Library of Congress Control Number: 2018965214
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Foreword: Biochemistry and Cell Biology
of Ageing – Parts I and II
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 “threescore
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: Biochemistry and Cell Biology of Ageing – Parts I and II
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, Newcastle University Thomas B. L. Kirkwood
Institute for Ageing, Newcastle upon Tyne, UK
Preface
This book, Biochemistry and Cell Biology of Ageing: Part I, Biomedical Science
(along with Part II, Clinical 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, and the two books covering Biomedical Science
and Clinical Science were duly commissioned.
We have attempted to compile a list of chapters written by authoritative authors
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 Biological Science chapter stands
firmly on its own merit, with correlation to the Clinical Science book chapters in
some cases. Over recent decades, ageing research has expanded enormously world-
wide, responding to the increased importance to the general population, 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 fundamental biomedical science within the field
of ageing research. We hope that the book will be of value to undergraduate bio-
medical science students, medical students, postgraduate researchers, and academ-
ics involved and interested in aspects of ageing research.
Johannes Gutenberg University J. Robin Harris
Mainz, Germany
Newcastle University Viktor Korolchuk
Newcastle upon Tyne, UK
July, 2018
vii
Contents
1 Antioxidant Vitamins and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Irina Milisav, Samo Ribarič, and Borut Poljsak
2 Autophagy: ‘Self-Eating’ Your Way to Longevity . . . . . . . . . . . . . . . . 25
Charlotte J. Pattison and Viktor I. Korolchuk
3 Nutrient Sensing, Signaling and Ageing: The Role of IGF-1
and mTOR in Ageing and Age-Related Disease . . . . . . . . . . . . . . . . . . 49
Simon C. Johnson
4 The Interplay Between Cholesterol Metabolism
and Intrinsic Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 99
Mark Tomás Mc Auley
5 Key Age-Imposed Signaling Changes That Are Responsible
for the Decline of Stem Cell Function . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Melod Mehdipour, Yutong Liu, Chao Liu, Binod Kumar,
Daehwan Kim, Ranveer Gathwala, and Irina M. Conboy
6 Creatine, Creatine Kinase, and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Nathalie Sumien, Ritu A. Shetty, and Eric B. Gonzales
7 Extracellular Matrix and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 169
Helen L. Birch
8 Vitamin D and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 191
Tom R. Hill, Antoneta Granic, and Terence J. Aspray
9 Telomeres, Telomerase and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 221
Gabriele Saretzki
10 Nuclear DNA Damage and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . 309
Kyriacos Agathangelou, Zisis Apostolou, and George A. Garinis
11 Signal Transduction Pathways in Ageing . . . . . . . . . . . . . . . . . . . . . . . 323
Cathy Slack and Jennifer Tullet
ix
x Contents
12 The Gut Microbiota and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 351
Claire Maynard and David Weinkove
13 Nutrition and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 373
Fiona C. Malcomson and John C. Mathers
14 Role/s of ‘Antioxidant’ Enzymes in Ageing . . . . . . . . . . . . . . . . . . . . . 425
Elizabeth Veal, Thomas Jackson, and Heather Latimer
15 B Vitamins and Ageing . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 451
Kathleen Mikkelsen and Vasso Apostolopoulos
16 Gene Expression, Epigenetics and Ageing . . . . . . . . . . . . . . . . . . . . . . 471
Babukrishna Maniyadath, Namrata Shukla,
and Ullas Kolthur-Seetharam
17 Glycobiology of Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 505
Fabio Dall’Olio