Current Aging Science
Volume 1, 3 Issues, 2008
ISSN: 1874-6098 (Print)
ISSN: 1874-6128 (Online)
Current Aging Science
Volume 1, Number 2, July 2008
Contents
Extending Life Using Tissue and Organ Replacement
Pp. 73-83
Anthony Atala
[Abstract]
Dietary Habits of Mongolian People, and Their Influence
on Lifestyle- Related Diseases and Early Aging Pp.
84-100
Fumio Komatsu, Yasuo Kagawa, Terue Kawabata,
Yoshinori Kaneko, Baatar Purvee, Jugder Otgon and Ulziiburen
Chimedregzen
[Abstract]
Effects of Aging on Thyroidal Function and Proliferation
Pp. 101-104
Vania M. Corrêa da Costa and
Doris Rosenthal
[Abstract]
Intraventricular Implant of Encapsulated CNTF-Secreting
Fibroblasts Ameliorates Motor Deficits in Aged Rats Pp.
105-111
Dwaine F. Emerich, Christopher G. Thanos
and Paul R. Sanberg
[Abstract]
Inflammation and Age-Related Iron Accumulation in
F344 Rats Pp. 112-121
Randy L. Hunter, Mei Liu, Dong Young Choi,
Wayne A. Cass and Guoying Bing
[Abstract]
The Interface Between Alzheimer’s Disease,
Normal Aging, and Related Disorders Pp. 122-132
Richard A. Armstrong
[Abstract]
Mood, Memory and Movement: An Age-Related Neurodegenerative
Complex? Pp. 133-139
Ann-Charlotte Granholm, Heather Boger and
Marina E. Emborg
[Abstract]
An Observational Study of the Needs and Quality of
Life Amongst Patients in the Treatment of Alzheimer’s
Dementia with Cholinesterase Inhibitors Pp.
140-143
Wendy E. Ward and Kunle A. Ashaye
[Abstract]
Book Review
Mild Stress and Healthy Aging: Applying Hormesis in
Aging Research and Interventions Pp. 144
Mahendra K. Thakur
[Abstract]
Abstracts
[Back to top]
Extending Life Using Tissue and Organ Replacement
Anthony Atala
There is a critical shortage of organs available for
donation to patients suffering from degenerative diseases
of various organ systems. This shortage becomes more severe
yearly, as the aging population grows and such diseases become
more common. The fields of regenerative medicine and tissue
engineering now offer hope for these aging patients with new
advances in material science, cell transplantation, and bioengineering.
Novel methods and materials to construct biological substitutes
for diseased and injured tissues are being developed, and
the goal is to restore and maintain normal function to the
patient. The field of stem cell research is rapidly advancing,
offering unforeseen options for treatment. For example, therapeutic
cloning, where an enucleated oocyte receives a donor cell
nucleus, yielding pluripotent stem cells, offers a potentially
limitless source of cells for tissue engineering applications.
However, recent discoveries in this field indicate that the
use of non-controversial cells and tissues also has enormous
potential for tissue engineering purposes. This article gives
an overview of recent advances in regenerative medicine and
describes their applications in tissue and organ replacement
technology, as well as how these technologies offer new therapies
to a person facing end-stage organ failure. There is a growing
optimism that the successes in this field will achieve the
goal of significantly extending the life of the patient.
[Back to top]
Dietary Habits of Mongolian People, and Their Influence
on Lifestyle- Related Diseases and Early Aging
Fumio Komatsu, Yasuo Kagawa, Terue Kawabata,
Yoshinori Kaneko, Baatar Purvee, Jugder Otgon and Ulziiburen
Chimedregzen
Mongolians are known to have relatively short life expectancy.
In order to examine the role of dietary habits in the early
aging of Mongolians, the food intake inquiry, anthropometric
measurements and blood clinical tests were performed for 365
healthy inhabitants in Murun, a northern Mongolia city, and
compared to those of Japanese. Murun inhibitants were found
to have a characteristic dietary habit of taking large amounts
of meat, milk, dairy products and wheat flour products, in
contrast little vegetables, fruits and fishes. The daily calorie
intake of the adults was estimated to be 2,525 kcal, and the
fat/total calorie ratio was calculated 33.7%, about 1.3-fold
higher than that of Japanese. The intake ratio of fatty acid
from the Mongolian foods, saturated : mono-unsaturated : poly-unsaturated
fatty acids (PUFA) ratio, was 10.3 : 7.8 : 3.0. Results of
blood clinical tests showed significantly higher levels of
serum triglycerides, low-density lipoprotein cholesterol (LDL)
and homocysteine, and lower levels of high-density lipoprotein
cholesterol (HDL), n-3 PUFA, folic acid and adiponectin, in
comparison with those of Japanese. In addition, the Mongolians
were also found to have significantly high levels of oxidative
stress markers, such as serum malondialdehyde-modified LDL
(MDA-LDL), urinary 8-hydroxy-2’-deoxyguanosine (8-OHdG)
and serum reactive oxygen metabolites (ROM). The serum ROM
level in the Mongolians seemed to associate with their body
fat ratio (p<0.05), and was significantly inverse-correlated
to handgrip strength (p<0.001). Obesity was observed at
a high incidence in the subjects over 30-year old, and over
40-year old their handgrip ability was markedly decreased.
These findings suggest that in the Mongolians the dietary
habits associate with their lifestyle-related diseases and
early aging, and the improvement of dietary habits is an effective
strategy for health promotion of the inhabitants.
[Back to top]
Effects of Aging on Thyroidal Function and Proliferation
Vania M. Corrêa da Costa and
Doris Rosenthal
The endocrine system is as affected by aging as are other
systems. The effect of aging on the hypothalamus-pituitary-thyroid
function is still controversial. Human aging was reported
as associated with a decrease in thyrotropin (TSH) secretion,
but increased TSH levels in relatively healthy elders are
also reported. The main point discussed is whether this increase
in the immunoreactive TSH of aged subjects, and related changes
in thyroid function, are “physiologic” consequences
of aging on the hypothalamus-pituitary-thyroid axis or are
induced by non-thyroid illnesses and/or drug use, frequent
in the elderly. There are strong evidences of decreased hypothalamus-pituitary-thyroid
axis activity as well as decreased thyroxine metabolism (5’-deiodination)
in humans, and other mammals. For now, we must consider that
the hypothalamus-pituitary-thyroid axis is affected at all
three levels by normal aging, and the mild state of “total”
hypothyroidism during aging is completed by a reduced response
of target cells/tissues to thyroid hormones. Despite the decreased
response of the old rat thyroid to TSH there is no decrease
in the glands mass. Ras proteins are involved in the transduction
of growth factor signals by surface receptors, in thyroid
as well as in other tissues, and are key components of downstream
signaling through several pathways. Ras activation of Raf,
and of extracellular-signal-regulated kinases (ERK) is an
important signaling pathway for many Ras effects. Very little
is known about the modulation of Ras expression in the aging
thyroid. We detected an increase in Ras expression in thyroids
of old rats, but the signal transduction by pERK was decreased,
suggesting that another RAS-signaling pathway could be activated
and responsible for the maintenance of the thyroid volume.
[Back to top]
Intraventricular Implant of Encapsulated CNTF-Secreting
Fibroblasts Ameliorates Motor Deficits in Aged Rats
Dwaine F. Emerich, Christopher G. Thanos
and Paul R. Sanberg
The impact of intraventricular ciliary neurotrophic factor
(CNTF) on motor function in aged rats was evaluated. Spontaneous
locomotion and motor coordination were quantified in young
(5-6 months) and aged (24-25 months) rats. Relative to young
animals, aged rats were significantly less active, fell more
rapidly from a rotating rod, and were unable to maintain their
balance on a wooden beam. Aged animals received bilateral
intraventricular implants of polymerencapsulated fibroblasts
that were genetically modified to secrete CNTF. Controls received
either no implant or capsules loaded with mock transfected
cells. One month after implantation the aged animals that
received CNTF implants were significantly more active and
were improved on the rotorod and beam balance tests. The improvement
in performance on the rotorod and beam balance tests was dependant
on the task difficulty and dissipated at higher rotations
(rotorod) and smaller beam widths (beam balance). No recovery
was seen in aged animals receiving control implants. Postmortem
removal of the encapsulated cells confirmed that they continued
to secrete CNTF. These data are the first to suggest that
intracerebral delivery of CNTF might be useful for slowing
or reversing age-related changes in motor function.
[Back to top]
Inflammation and Age-Related Iron Accumulation in
F344 Rats
Randy L. Hunter, Mei Liu, Dong Young Choi,
Wayne A. Cass and Guoying Bing
Evidence suggests chronic inflammation and iron accumulation
may play a role in the pathogenesis of Parkinson’s disease
(PD) as inflammation and iron levels increase with age and
appear in the disease pathology. It is hypothesized that an
aggravated inflammatory response and iron accumulation, as
a function of age, increase oxidative stress and participate
in the pathogenesis of PD. Intracranial injection of the bacterial
endotoxin, lipopolysaccharide (LPS), has been shown to induce
microglia activation, oxidative stress, mitochondrial impairment,
iron accumulation, and dopaminergic neurodegeneration within
the substantia nigra. We tested the hypothesis that injection
of LPS into the striatum would increase iron accumulation
in the substantia nigra of aged rats compared to young ones.
Our results showed that four weeks post injection, LPS significantly
increased microglia activation, lipid peroxidation, ferritin
expression, and total nigral iron content in aged rats. In
addition, LPS significantly altered the turnover ratio of
homovanillic acid to dopamine. Thus, an age-related increase
in iron as well as susceptibility to inflammation may play
an important role in PD-related neurodegeneration, as free
radicals produced from the inflammatory response can become
more toxic through increased ferrous iron catalyzed Fenton
Chemistry. This may enhance oxidative stress, exacerbate microglia
activation, and drive the progression of PD.
[Back to top]
The Interface Between Alzheimer’s Disease,
Normal Aging, and Related Disorders
Richard A. Armstrong
Since the earliest descriptions of Alzheimer’s
disease (AD), the presence of senile plaques (SP) and neurofibrillary
tangles (NFT) have been regarded as the typical pathological
hallmarks of the disease. Studies over the last twenty years,
however, have reported a considerable degree of heterogeneity
within the AD phenotype and as a consequence, an overlap between
the pathological features of AD not only with normal aging,
but also with disorders related to AD. This review discusses:
1) the degree of heterogeneity within AD, 2) the concept of
an ‘interface’ between disorders, 3) the nature
and degree of the interface between AD and normal aging, vascular
dementia (VD), the tauopathies, synucleinopathies, and prion
disease, and 4) whether the original status of AD should be
retained or whether AD, normal aging, and the related disorders
should be regarded as representing a ‘continuum’
of neuropathological change.
[Back to top]
Mood, Memory and Movement: An Age-Related Neurodegenerative
Complex?
Ann-Charlotte Granholm, Heather Boger and
Marina E. Emborg
The following review was constructed as a concept paper
based on a recent workshop on neurodegenerative disease sponsored
by the National Institute on Aging (NIA), the American Geriatric
Society (AGS), and the John A. Hartford Foundation. The meeting
was entitled "Thinking, moving and feeling: Common underlying
mechanisms? 4th Annual Bedside-to-Bench Conference”
and had the purpose to connect current basic and clinical
findings on common brainrelated alterations occurring with
aging such as depression, movement disorders, and cognitive
decline. Many prominent researchers expressed their opinion
on aging and it was revealed that age-related brain dysfunction
of any kind seems to share several risk factors and/or pathways.
But can something be done to actively achieve "successful
aging"? In this review, based largely on the workshop
and current literature, we have summarized some of the current
theories for depression, movement and cognitive impairment
with aging, as well as potential preventive measures. We have
also summarized the emerging need for relevant animal models
and how these could be developed and utilized.
[Back to top]
An Observational Study of the Needs and Quality of
Life Amongst Patients in the Treatment of Alzheimer’s
Dementia with Cholinesterase Inhibitors
Wendy E. Ward and Kunle A. Ashaye
Alzheimer’s dementia is one of the most commost mental
health disorders associated with aging. In its earlier stages
sufferers live independently but gradually rely increasingly
on loved ones or formal carers for support as the illness
progresses. Its treatment involves both medical and social
care. This study assesses the impact of outpatients’
care and cholinesterase inhibitors in patients being treated
for Alzheimer’s dementia.
The needs and quality of life of patients attending an outpatients
dementia care service were assessed using the Camberwell Assessment
of Need for the Elderly (CANE) and Quality of Life in Alzheimer’s
Disease: Patient and Caregiver report. Other tools used were
the Problems Checklist and Carer Strain, the Minimental State
Examination (MMSE) and a proforma to obtain sociodemographic
details. All patients who had informal care were assessed
using the questionnaires.
104 patients were seen of whom 34 were new and 70 were follow-up
patients. 43 patients lived alone while the rest lived with
their spouses or other relatives such as children. There was
reduction in the number of CANE unmet needs and increased
combined Quality of Life in Alzheimer’s Dementia scores
in the first three months amongst the newly referred patients.
The findings suggest that outpatients’ dementia care
and prescribing of cholinesterase inhibitors helped to meet
the needs of patients and improve patients’ quality
of life in first three months.
[Back to top]
Mild Stress and Healthy Aging: Applying Hormesis in
Aging Research and Interventions
Mahendra K. Thakur
As there is a rapid rise in the elderly population and
incidence of related old age diseases, an emerging social
challenge is to maintain health throughout ones lifespan.
In this context, the present book is timely written by experts
in the subject and pre-sents state-of-art status of research
on hormesis and aging. Although the book is multi-authored,
chapters are highly coordinated. It aims to explore whether
hormesis can be used for healthy aging of human beings and
presents excellent and interesting information on hormesis
with respect to aging. The editors, Eric Le Bourg and Suresh
I.S. Rattan, are leading researchers and popularly known for
their longstanding contributions in the area of aging and
hormesis.
The book comprises 10 well-written chapters covering a wide
range of topics on hormesis and aging. Each chapter is thoroughly
discussed and provides new information. The first two chapters
deal with detailed introduction of hormesis and aging, the
next five chapters discuss hormetic effects of various types
of stresses, and the last three chapters are concerned with
clinical applications of hormesis. At the end, it is concluded
how hormesis can be useful for healthy aging, though the underlying
mechanism of action is not clearly understood.
The book begins with an excellent introduction and brief historical
analysis of hormesis and aging by the editors. The second
chapter by Edward Calabrese further explains the phenomenon
of hormesis and focuses on its use in gerontological research.
The third chapter written by Alexander Vaiserman describes
the beneficial effects of low dose irradiation on the longevity
of fruitflies, nematodes, rodents and human beings. The next
chapter by Eric Le Bourg presents results of hormetic effects
of hypergravity on aging and longevity of D. melanogaster.
The following chapter by Jesper Sorensen and colleagues focuses
on the use of extreme temperatures, either hot or cold in
D. melanogaster. The next chapter by the editor Suresh
Rattan himself describes the effects of mild stresses on human
cells, mainly fibroblasts. Focusing on rodents and human beings,
Li Li Ji shows that an increased physical activity can act
as a mild stress with hormetic effects. The last three chapters
are concerned with clinical applications of hormesis. Brian
Morris discusses the use of hormetic compounds for health
benefits. Pasquale Abete and Franco Rengo present evidences
to show how mild stress can be used to protect the aging heart
from pathological insults. Akmal Safwat argues that low dose
whole body irradiation enhances the efficiency of immune system.
Finally, in conclusion, all authors emphasize the perspectives
for human beings mentioning that hormesis can be used as an
effective anti-aging, health-promoting and lifespan-extending
strategy. The book is thought provoking and opens an exciting
new area for detailed study. It would be highly useful for
young researchers in biogerontology as well as for the established
biogerontologist to analyse their results in the light of
hormetic effects. Thus the book is worth reading by not only
biogerontologists but by all those who are interested in understanding
the hormetic approach for healthy aging.
Mahendra K. Thakur
Department of Zoology
Banaras Hindu University
Varanasi 221005, India
E-mail: mkt_bhu@yahoo.com
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