Proponent 1:
The views expressed by the
presenter are for the purposes of debate and do not necessarily represent his
own opinions, nor are they intended to represent in any way the opinions or
other views of the AGHE. Prepared and presented by Kenneth Kaloustian.
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I am going to argue in favor of extending longevity from the point of view of
both the average and maximum life span. In
fact, we have already significantly increased the average life span in humans;
what has not changed is the maximum life span.
“I could stay young and chipper and I’d lock with a zipper if only I had a
heart,” a quotation from the Tin
Man in the movie Wizard of Oz (Science, February 8, 2002). The recent advances
in biotechnology may yet offer help to the Tin Man and to countless other
individuals devastated with such diseases as cancers and cardiovascular
disorders. For example, as
indicated in the same issue of Science, bio-artificial liver devices are
currently being made composed of liver cells nurtured in a bioreactor to provide
support to a diseased liver until it can regenerate.
There are many other examples of recent discoveries that not only extend
the maximum life span but also the quality of life which I will describe later.
Obviously, we have to be extremely careful in venturing into new fields without
proper knowledge of the consequences. Jeremy
Rifkin in his book “The Biotech Century” warns the public against the
unchecked pace at which genetic engineering and the computer evolution is
advancing. Although he does not
dispute the promised benefits of biotechnology, he warns that we must closely
consider its negative consequences.
I tell my students that aging is probably the only mechanism that humans have
tried to elucidate throughout the history of mankind and, if research in this
area is continued with utmost responsibility, the benefits far outweigh the
risks. I also provide the students
with some examples of men’s attempts to reverse aging such as, reconstruction
of the nose by tissue grafting in 1597, blood transfusion between two dogs in
1666, repair of human skull with dog skull in 1682, etc.
Although we use biotechnology in an attempt to improve on longevity, this
process actually occurs naturally. In
most populations, small subset, less than 1%, live significantly longer.
For example, in the Mediterranean fly, C. capiata, average
life span is 25 days; average life
span for less than 1% is 55 days.
There are many examples of scientific intervention that extend life span.
The following are examples of recent achievements in this area:
In Drosophila melonogaster, CuZn SOD gene, Mn SOD gene and
catalase glutathione S-transferase gene up-regulation increases longevity,
possibly due to decrease in oxidative damage.
In transgenic work showing overexpression of CuZnSOD, CAT and MnSOD
either alone or in combination increase life span.
Heat shock protein (hsp) overexpression also shows the same results.
These proteins protect cells under stressful conditions.
In mice, overexpression of CuZnSOD does not increase life span, but
underexpression of MnSOD decrease life span and morbidity.
However, caloric restriction
in mice increases overexpression of CuZnSOD and CAT and decreases oxidation
damage in muscle.
Interestingly, the changes mentioned above (Enzymes and caloric restriction) in
all species decrease oxidative stress and metabolic rate but in Drosophila the
decrease is in oxidative damage only with no change in metabolic rate.
Somatic gene surgery, gene therapy, as well as apoptotic gene manipulation have
also shown to have influence on life span.
For example, insertion of apoptotic gene promotors in human cells from
the roundworm C. elegans induces human cells to commit suicide.
Apparently this mechanism is highly conserved during evolution.
Recently, genetic “surgery” in mice lacking immune function was
performed successfully using stem cell therapy.
Recent advances with telomere research has elucidated some aspects of cellular
aging. Telomeres cap the ends of
linear chromosomes. They allow cells to distinguish the chromosome ends for
double strand DNA breaks. They also prevent degradation or fusion of chromosome
ends and function in gene expression (Telomere length ranges between 15-20Kb in
humans but 30 to >
50Kb in mice). In humans when
telomere size is reduced to 4-7Kb, cells stop dividing and die.
The presence of the enzyme telomerase maintains normal telomere length.
However, most somatic cells do not express telomerase except in skin
cells (stem) and human T-cells. Both
sperm and ovum express telomerase. Introduction of the gene for telomerase in
human as well as other animal cells maintains normal telomere length
and prevents cellular death. Currently,
investigators are looking at the possibilities of telomerase therapy to delay or
even stop cellular aging.
Recent discoveries and advances have certainly raised the expectations of many
scientists in respect to extending maximum life span. At last years AGHE meeting I presented a paper on stem cells
and refer the reader to that paper for more complete detailed information on
stem cells and aging. Briefly,
these are few examples of stem cells functions in respect to aging:
Transplantation of embryonic stem cells into injured spinal cord has promoted
functional recovery in the rat.
In monkeys with demyelinated lesion, stem cells are converted into glial cells
to form new myelin.
Mice, injected with virus to mimic amyotropic lateral sclerosis (ALS), injected
with stem cells show significant improvements.
The question then is what to do? What
are our responsibilities?
Although some scientists do their research solely because of its intrinsic
interest, most, however, understand the much broader implications and behave in
a responsible manner. Therefore, I
try to emphasize to my students that the tools that we need to study aging and
possibly delay the process of aging is currently available to us.
How we use these tools in a responsible manner is the critical issue that
we should be concerned about !
Therefore, we may decide not to use the term longevity (since this does not
answer the question on the quality of life) but rather the terms "youngevity" and
"healthivity."
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Prepared and presented by
Kenneth Kaloustian.
Copyright 2002: Kenneth Kaloustian,
Professor of Biology,
Quinnipiac University, Kenneth.Kaloustian@quinnipiac.edu