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