Table Of ContentPramod C. Rath · Ramesh Sharma
S. Prasad Editors
Topics in
Biomedical
Gerontology
Topics in Biomedical Gerontology
Pramod C. Rath Ramesh Sharma
(cid:129)
S. Prasad
Editors
Topics in Biomedical
Gerontology
123
Editors
PramodC. Rath S. Prasad
Molecular Biology Laboratory,School Biochemistry andMolecular Biology
ofLife Sciences Laboratory,Departmentof Zoology
Jawaharlal Nehru University Banaras HinduUniversity
NewDelhi, Delhi Varanasi, Uttar Pradesh
India India
RameshSharma
Department ofBiochemistry
NorthEastern Hill University
Shillong,Meghalaya
India
ISBN978-981-10-2154-1 ISBN978-981-10-2155-8 (eBook)
DOI 10.1007/978-981-10-2155-8
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Dedicated to our teacher Prof. Madhu Sudan
Kanungo (1927–2011)
A world-class Indian Biochemist and
Gerontologist who devoted his entire career
of teaching and research to Biochemistry of
Aging at the Banaras Hindu University
(BHU), Varanasi, India for 49 years. After
completing his Ph.D. under Prof. C.L.
Prosser at the University of Illinois, USA, he
joined the Department of Zoology, BHU in
early 1960s and continued until the end. He
was always actively involved in teaching and
research and developed an excellent teaching
and research program of Animal
Biochemistry and produced several Ph.D.
students as next generation of teachers and
scientists in many universities and institutes
of India and abroad. He published 150
research papers and authored two books on
aging: Biochemistry of Aging (Academic
Press, 1980) and Genes and Aging
(Cambridge University Press, 1994). He
received numerous prestigious scientific
recognitions for research (notably
S.S. Bhatnagar Prize, Fellows of all the
Indian Science Academies, Jawaharlal Nehru
Fellowship, Emeritus Professorship of BHU)
and civilian award (Padmashree). His
dedication to teaching and research has been
exemplary. He founded and was President
and Patron of the Association of Gerontology
ofIndia(AGI).Heisregardedasthefatherof
agingresearchinIndia.Herepresentedmany
national and international bodies concerned
with aging and policies for the elderly.
Foreword I
Aging is an intrinsic biological process from which
there is no escape (Arking 2003, Kanungo 2003,
Kirkwood 2002). Now biological investigations of
aging have grown into cutting-edge science (Morley
2004). Understanding why aging occurs may help
devise means to counter or modulate our aging by
alteringtheagingprocessandsenescence.Howtolive
longer and add life to years so that the elderly live in
good health is the main aim of aging research.
Experimentalresearchonaginginlaboratoryanimals
continues to provide information about multiple delete-
riousbiologicalandmoleculareventsthataccumulatein
different tissues over time and gradually reduce an organism’s physiological effec-
tiveness, state of maintenance, and health. Such studies give information about phys-
iological ages—measurement of physiological processes involved in aging (Wolow
et al. 2010). Furthermore, insight into the mechanisms underlying the cellular and
molecular changes that can contribute to senescence is of great interest.
It can be argued that an adult’s overall health will remain stable if gene
expression remains stable (Rao et al. 1996). Microarray determination of the gene
expression patterns between young and old subjects has shown relationships
between alterations in gene expressions and aging.
There exists, however, no specific gene that may cause aging as no gene has
been evolutionarily selected for aging (Kirkwood 2002). However, experimental
manipulation of specific genes has been reported to extend life span of some
organisms. Organisms are said to be programmed for survival and not for death.
Genesinfluencing aging are those that affect thedurability and maintenance of the
soma. That is why; the subject of genomics/gene action in aging is of paramount
importance. Study of model organisms for aging research, e.g., Drosophila,
Caenorhabditis,and Saccharomyces haveshown that there are genes that alterthe
rateofaging.Thus,organismsaregenetically programmedtosurvivealthoughthe
vii
viii ForewordI
programisnotefficientenoughtomakethemlastindefinitely.Efficientmechanisms
for somatic maintenance and repair (genetic mechanisms of longevity assurance)
can secure long and healthy life span. So aging occurs because organisms fail to
make required energy allocations for somatic maintenance and repair (Arking
2003). Therefore, some interventions should be possible to retard/slow aging. The
fieldofhealthyagingmedicinehasalsoemerged(Ohlanskyetal.2004;Disterhoft
and Oh 2006).
In experimental studies, calorie restriction has been found to reduce the devel-
opmentofmanynormalandpathologicalmarkersofagingandtoslowtheintrinsic
aging rates (Sharma 2004). It brings about changes that help maintaining the
optimalfunctionoftissues.Ithasbeenfoundtolengthenprimatelives.It,however,
remains to be seen how it will benefit humans. Undernutrition mimicking dietary
caloric restriction was shown to be actually beneficial in human subjects in main-
taining good DNA repair capacity (Rao et al. 1996). Oxidative stress is seen as a
major contributor to the aging process. Thus anti-oxidative measures pharmaco-
logically have been found to reduce aging. Increasing the level of genetic defense
mechanisms against oxidative stress is also of significance.
This volume “Topics in Biomedical Gerontology” presents aging research data
atmolecular,cellular,andorganismallevelsonawidespectrumofsubjectsderived
from animal models such as Drosophila, Dictyostelium, mouse, rat, and also
humans.
Data on human aging are reported in three papers. Frailty is an important
expression of aging—like process in humans, and down regulation of sirtuins is
showntobeabiomarkerofthisprocess.Howmorphologyofthehumanpancreasis
altered during development and aging is described in an interesting paper. The
agingnervoussystemencompassesseveralresearchareas.Apaperhasshownhow
aging affects the population of neurons and glia in human cochlear nucleus.
Thelysosomalandautophagypathwaysarebothinvolvedduringnormalaging.
Autophagytendstodeclineduringnormalaging,anditislikelytobeimportantfor
promotinghealthyaging.Describedinanexperimentalpaperaredatafromstudies
onDictyosteliumdiscoideum,whichshowhowautophagypromoteslifeextension.
Neurons are post-mitotic cells, which cannot divide to replace damaged or
deteriorated cells. Thus, accumulated damage from oxidative stress has been con-
sideredakeyfactorcontributingtonormalagingofthenervoussystem(Poonetal.
2004). The paper on oxidative stress in the brain highlights the role of oxidative
stressinbrain’scognitiveaging.Howoxidativestressinfluencesothertissuessuch
as kidney is also described.
Electrical activity is the functional basis of the nervous system. Aging of the
brain involves changes in its electrophysiological activity and age-related disor-
ganization of electrical activity causes derangement of neural and cognitive func-
tions (Disterhoft and Oh 2006). There is thus a potential link between
electrophysiological and behavioral consequences of aging.
Thattheanti-agingneurosteroiddehydroepiandrosteronemayhaveantiepileptic
influence on the nervous system of elderly is shown in an experimental study.
A number of papers included in this volume also present information concerning
ForewordI ix
anti-aging influence of calorie restriction, e.g., down-regulation of insulin-like
growth factor-1 and upregulation of cardiac and skeletal muscle inorganic
pyrophosphatase. Experimental data on the role of noncoding RNA and Pax-6
transcription factor are described during aging. Also, a review on chromatin and
aging is of interest.
AmajorneurodegenerativediseaseassociatedwithagingisAlzheimer’sdisease
inwhichamyloid-bproteinpathologyplaysanimportantrole(Mishraetal.2016).
The paper on amyloid pathology attempts to show how this may cause behavioral
changesinthecontextofhuman-specificbehaviorsuchasempathy,sympathyand
pro-social tendency in rats.
Disorders such as diabetes, depression as well as dietary factors can enhance
decline of the nervous system function. A paper examines how experimentally-
induced diabetes mellitus type 2 induces brain aging and memory impairment and
how these two effects are prevented by Bacopa monnieri. In another paper how
recoveryfromage-relatedmemorylossmaybepossibleisdescribed.Healthyaging
through the principles of Ayurveda has also been described.
Rameshwar Singh
Formerly Professor of Neurobiology
School of Life Sciences, Jawaharlal Nehru University
New Delhi
References
ArkingR(2003)Aging:abiologicalperspective.AmSci91:508–515
DisterhoftJF,OhMM(2006)Pharmacologicalandmolecularenhancementoflearninginaging
andAlzheimer’sdisease.JPhysiolParis99:180–192
KanungoMS(2003)Mechanismofaging.ProcIndianNatSciAcadB69:121–140
KirkwoodTBL(2002)Evolutionofaging.MechAgingDev123:737–745
Mishra N, Singh R, Sharma D (2016) Differential response of amygdala and hippocampus
consequenttoAb40andAb42—inducedtoxicityintheratbrain:acomparativestudy.IntJ
AdvRes4:959–994
MorleyJE(2004)Thetop10hottopicsinaging.JGerontolMedSci59A:24–33
OhlanskySJ,HayflickL,PerlsTT(2004)Anti-agingmedicine:thehypeandthereality—Part1.
JGerontolBiolSci59A:513–514
PoonHF,CalabreseV,ScapagniniG,ButterfieldDA(2004)Freeradicals:keytobrainagingand
hemeoxygenaseasacellularresponsetooxidativestress.JGerontolMedSci59A:478–493
RaoKS,AyyagiriS,RajiNS,MurthyKJR(1996)Under-nutrition andageing:effectsonDNA
repairinhumanperipherallymphocytes.CurrSci71:464–469
SharmaR(2004)Dietaryrestrictionanditsmultifacetedeffects.CurrSci87:1203–1210
Wolow CA, Zou S, Mattson MP (2010) Aging of the nervous system: In: Wolf NS (ed) The
comparativebiologyofaging.SpringerScience+BusinessMediaBV,pp319–352
Foreword II
Thegrayingoftheworldpopulationisoneofthemost
seriousissuesinthetwenty-firstcentury.Thelifespan
of people in developed as well as developing coun-
tries has been increasing during the past several
decades and appears to increase further (Vaupel
2010). This is a good news, but it has also caused
increaseinthenumberoffrailand/ordiseasedelderly
people,puttingaheavysocial,economical.andfamily
burden on younger generations in many countries.
It is often stated by geriatric physicians that the
majorriskfactorinthedevelopmentofage-associated
diseases such as dementia and cardiovascular disor-
ders is aging itself. This implies that biological changes with aging are likely to
underlie the etiology and progress of the diseases in addition to causing the
physiological impairments in many tissues although aging is not a disease.
Biomedical Gerontology is therefore important not only as a basic science to
unravel the mechanisms of biological aging, but also to extend health span of
people,reducingrisksofage-relateddiseases,andimprovingtheactivitiesofdaily
living to retard the decline of quality of life with aging. Aging is very complex
biological phenomena as represented in drawings of the famous Indian legend
“The blind men and the elephant,” symbolizing that a big complex object may be
recognizedasdifferentthingsifexaminedinpartdependingonfromwhichsideitis
viewed. In fact, more than three hundred theories have been proposed for mecha-
nisms of biological aging already many years ago (Medvedev 1990), and the
number is still increasing and the theories are being modified (Goto 2015).
This comprehensive book covers a wide range of major current topics on aging
inbothbasicandappliedfieldsbyexpertIndianscientistsincludingdisciplesoflate
Prof. Madhu Sudan Kanungo, my old friend, the founder of Indian biomedical
gerontology and the leader of aging research in Asian countries. He was already
well known internationally when I started the research on aging forty years ago.
xi
