Models, Molecules and Mechanisms in Biogerontology: Cellular Processes, Metabolism and Diseases

497 Pages·2020·10.47 MB·English

by  Pramod C. Rath (editor)

Pramod C. Rath Editor
Models,
Molecules and
Mechanisms in
Biogerontology
Cellular Processes, Metabolism and
Diseases
Models, Molecules and Mechanisms
in Biogerontology
Pramod C. Rath
Editor
Models, Molecules
and Mechanisms
in Biogerontology
Cellular Processes, Metabolism
and Diseases
Editor
Pramod C. Rath
School of Life Sciences
Jawaharlal Nehru University
New Delhi, India
ISBN 978-981-32-9004-4 ISBN 978-981-32-9005-1 (eBook)
https://doi.org/10.1007/978-981-32-9005-1
© Springer Nature Singapore Pte Ltd. 2020
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Purna Chandra Rath
(8 October 1889–1 May 1982)
This book is dedicated to Kaviraj Purna
Chandra Rath (1889–1982), an exponent of
Ayurveda, the ancient Indian traditional
science of life, health, and medicine, who
lived up to the age of 93 without any major
health issue in the holy city of Puri situated
in the state of Odisha on the east coast of the
Bay of Bengal in India. He was educated in
Sanskrit, Ayurveda, and prepared large
number of ayurvedic medicines from natural
medicinal herbs and other materials
according to the ancient ayurvedic scripts at
his home dispensary. He had successfully
practiced Ayurveda for 60 years for the
treatment of thousands of patients suffering
from various diseases across the state of
Odisha. He had played key role in the
establishment of ayurvedic schools and
trained next generations of experts, many of
them learnt the age-old science by staying
with him at his home as a “gurukul” free of
cost. For these exemplary contributions in
Ayurveda and public life, he was awarded
the prestigious title of “Vaidyaratna” by the
then viceroy of British-India in 1938. Purna
Chandra had written many books on
Ayurveda and poetry in Odia, the language
of Odisha which later became the sixth
classical language of India, for the benefit of
people. His biography was written by a
professor of Odia literature, describing the
journey of his life beginning as a village boy
to a highly acclaimed authority in Ayurveda,
who demonstrated the unmatched value and
utility of this ancient Indian traditional
medicine system for the society at a nominal
cost. This is an ideal example of healthy
aging of a socially relevant person who lived
in India several decades ago.
Original Address: Late Vaidyaratna Kaviraj
Purna Chandra Rath, South Gate, Puri-
752001, Odisha
Preface
Since life emerged in cellular form, two things must have become imminent, the cell
must propagate itself and there should be a limited lifespan of a cell. If cells do not
die, new cells will gradually become less and less in number and the population of
cells would soon stop making any more new cell. Such a population of cells will
ideally contain “senescent” cells or old cells. Thus, we have precursor cells (“stem
cells”), which are ready to divide; dividing cells; cells that do not divide any more –
hence becoming old cells; and cells undergoing the process of cell death. Therefore,
if old cells accumulate in a tissue or organ, it manifests expression of aging. If we
can remove old cells from tissues or organs, it would result in “rejuvenation” – a
process of reverse aging. Biological differences among stem cells, dividing cells,
senescent cells, dying or dead cells and rejuvenated cells constitute the entire spec-
trum of aging. Cellular aging is planned at the birth of a cell, so also for the tissues,
organs and organisms. Aging may finally eliminate a cell or an individual but keeps
the rest of the system or population young and active. Possibly, that is why aging
has been selected through evolution. However, we would like that the aging cell or
individual should remain free of major faults until the end. Hence, health-span is the
new name for longevity or lifespan. Health is wealth at all ages.
Biology of aging is both inherent and intrinsic to individual cells, the genetic
material (DNA) of cells, the cellular genomic information (DNA and RNA), non-
genomic component (proteins and membrane systems) and the network of events
(cell signalling pathways). The cellular compartmentalization (nucleus, mitochon-
dria, endoplasmic reticulum, lysosome and peroxisome) presents an organizational
and architectural design, where the processes of both life and death are executed.
Since biological processes have to be carried out by macromolecular assembly of
units of structure and function, be it chromatin-DNA, RNA-protein, protein-protein
complexes or structural designs of bio-membranes or polymers of sugar, lipid and
peptide, restrictions on temperature, pH, ionic concentration and osmolarity have to
be imposed to ensure native conformation, lower activation energy, efficient cataly-
sis, sustainable positive-negative regulations and recycling of resources.
Optimization of structure gives way to efficiency of catalysis and regulation.
Metabolic pathways establish foundation of cellular physiology. Utilization of
nutrients generates energy and releases free radicals such as reactive oxygen species
(ROS) and reactive nitrogen species (RNS). These cause oxidative stress in cells
due to oxidation of proteins, lipids and DNA/RNA. In order to keep it under control,
vii
viii Preface
cellular scavenger molecules have evolved either as enzymes (Glutathione-S-
transferase, catalase, super oxide dismutase, etc.) or as metabolites (glutathione,
ascorbic acid, etc.). A small amount of ROS activates cellular signalling and gene
expression but higher amounts of ROS cause disease.
During aging of cells and tissues in almost all organisms studied so far, oxidative
stress increases, telomeres at the chromosomal ends get shortened, the stem cell
reserves of the tissues get exhausted, the gene expression and regulation mecha-
nisms become less efficient, the metabolic pathways lose their balance, the protein
synthesis and regulation machinery gets affected, DNA damage increases and DNA
repair systems fall, mutations accumulate in the genomic DNA, low grade chronic
inflammation becomes persistent and immune responses against infections become
weaker, and senescent cells accumulate in tissues and organs. The old organism suf-
fers from decline of almost all physiological functions and becomes more prone to
age-related diseases ultimately leading to death. Thus although aging is not a dis-
ease, it invites many diseases. Diseases and human suffering are a curse but drugs
and medical treatments are a big market. Social values and cultural virtues in human
civilizations have always stood for humanity and nature. Scientific advancements
brought new knowledge into existence and gave birth to technology for further
development. Appropriate policies ensure development to be inclusive and plural in
human society. The need of the hour is to give a patient listening to the problems of
the elderly and extend a helping hand to those who have spent their life in hand-
holding in a socially relevant lifetime.
Models, Molecules and Mechanisms in Biogerontology: Cellular Processes,
Metabolism and Diseases contains two parts: (I) Alterations in Cellular Mechanisms
During Aging and (II) Alterations in Metabolism During Aging and Diseases. There
are 21 chapters written by authors from nine Indian university/institute(s) and three
university/institute(s) in the USA, Germany and Italy. Section I deals with 15 chap-
ters: protein structure and function, DNA replication, transcription and gene expres-
sion, ribosome and translation, transcription factors (p53 & Pax), telomere and
telomerase, epigenome and epigenetic rejuvenation, mitochondria and free radicals
(ROS), stem cells and model systems (Dictyostelium, Drosophila & Killifish) in
relation to aging and age-related diseases. Section II deals with six chapters: mus-
cle, metabolic diseases, nutrient sensing, protein aggregation, biological rhythms
and cancer in relation to aging. The concepts, molecules and mechanisms involved
in cellular processes linked to aging, longevity and age-related diseases are high-
lighted. There has been an attempt to link the basic biology with gerontology and
geriatrics in order to provide contemporary and cutting-edge information for basic
research and clinical situations. The text is designed for graduate students and
researchers. It could also help policy makers as well as public and private bodies in
the field of biomedical gerontology and geriatrics.
The editor of this book thanks all the authors who have contributed the chapters
unconditionally. Apologies are due for not being able to make a mention of all the
work done in this field. Some of us writing chapters for this book have been either
Preface ix
Master’s or Ph. D. students of Prof. M. S. Kanungo, our teacher, who started research
on biology of aging after founding the Biochemistry Section in the Department of
Zoology at Banaras Hindu University, Varanasi, India, as early as 1960s. We express
our sincere regards to his departed soul. The School of Life Sciences at Jawaharlal
Nehru University, New Delhi, India is acknowledged for all help.
New Delhi, India Pramod C. Rath
Contents
Part I A lterations in Cellular Mechanisms During Aging
1 Protein Structure and Function in Aging
and Age-Related Diseases . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3
Anshumali Mittal and Pramod C. Rath
2 DNA, DNA Replication, and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
Bhumika Sharma, Meetu Agarwal, Vijay Verma,
and Suman Kumar Dhar
3 Transcription and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
Malika Saint and Pramod C. Rath
4 Ribosome, Protein Synthesis, and Aging . . . . . . . . . . . . . . . . . . . . . . . . 67
Reetika Manhas and Pramod C. Rath
5 p53 and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 89
Nilambra Dogra and Tapas Mukhopadhyay
6 Paired Box (Pax) Transcription Factors and Aging . . . . . . . . . . . . . . . 109
Rajnikant Mishra
7 Telomeres, Telomerase, and Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119
Deepak K. Mishra, Ramraj Prasad, and Pramod Yadava
8 The Epigenome of Aging . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135
Rohini Muthuswami
9 Attaining Epigenetic Rejuvenation: Challenges Ahead . . . . . . . . . . . . 159
Jogeswar S. Purohit, Neetika Singh, Shah S. Hussain,
and Madan M. Chaturvedi
10 Mitochondria as a Key Player in Aging . . . . . . . . . . . . . . . . . . . . . . . . 181
Rupa Banerjee and Pramod C. Rath
11 Aging, Free Radicals, and Reactive Oxygen Species:
An Evolving Concept . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 199
Shyamal K. Goswami
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