---------- Forwarded message ----------
Date: Fri, 12 Apr 1996 07:42:13 -0400
From: Dennis Fink <DENFIN at aol.com>
To: Multiple recipients of list LONGEVITY <LONGEVITY at VM.EGE.EDU.TR>
Subject: Re: Telomere questions
In a message dated 96-04-11 05:07:29 EDT, Don wrote:
>Can you enlighten in lay terms?
Thanks for forwarding the very interesting material Don.
Until more research is done we just can't be sure how important being able
lengthen the lives of certain cells (by lengthening the telomeres) will be to
the overall aging process. I would think that this will be very useful in
certain situations but whether or not it is the primary cause of aging
remains to be shown, at least from what I have seen.
Kevin asked:
>Admittedly it is far too early to peg telomere shortening (loss? I don't
>know the proper terminology here) as the cause of ageing, but from what
>I read on the net there would seem to be a strong connection. Two
>questions come to my mind. First, is there some material that a
>person like myself (not a biology major) can read and understand on
>the subject? Second, to date, has any method been found that
>prevents or significantly slows down the rate of telomere shortening?
>It seems to me that the latter might place you in a bit higher risk of
>cancer than otherwise though.
>This will be a significant problem for lengthening cell lifespan without
increasing cancer risk. I'll include some material from my e-text which
addresses these issues and gives three references for more info. There are
even entire books on telomeres already but that is likely more than a non -
biologist wants.
>Recently I saw a TV interview in which some Ph.D. or other said that
>many cells in the human body were effectlively immortal. Do these
>cells (if this is true) achieve this via prevention of telomere
>shortening, and if so (and this is the big question here) do these
>kinds of cells show a greater tendency to go cancerous than other
>types of cells? If not, what prevents this?
>I'm not sure we have all these answers yet. The Scientific American work
referenced below described many cells as having sufficient telomere length
and replication rate that the telomeres do not seem to be important to aging
as it occurs today, at least for many cells.
Further, the cells that bear the brunt of aging (i.e., the brain
cells) don't even divide. Some of the other familiar changes of aging are
programmed genetically (eg., the loss of receptors from the erectile tissues,
which are also made up of non-dividing cells).
>All of this assumes that my questions are not so off base as to make
>no sense at all...
>
Your questions are right on target Kevin!
Out of context ASCII extracts (no italics, etc.) from my e-text, health70
(available at cost)
-------------------------
Carol Orlock in The End of Aging (p. 99) notes the similarity in the number
of cell divisions and lifespan in several animals.
She cites the gradually increasing lifespans of the mouse, chicken, human and
Galapagos tortoise, and the gradually increasing number of cell divisions of
14 to 28 (mouse), 15 to 35 (chicken), 50 to 60 (human) and 90 to 125
divisions for the long lived tortoise. Orlock, noting that by age seventy
five, we loose about a third of the cells that we had at peak cell count,
feels that it might be helpful to be able to extend the doubling time of
certain vital cells. In the case of the rare condition known as progeria,
which is essentially a disease of accelerated aging, Orlock states (p. 103)
that cells divide only about twenty times, whereas they might normally double
about 60 times. The decreased number of divisions appears to be due to
shortened telomeres (discussed more below), segments on the ends of
chromosomes which shorten with each cell division. There is more to aging
than just telomere length though since it varies considerably among people of
the same age, and some researchers say cells can usually divide more times
than is required in a human life span (Scientific American, February 1996, p.
95). Genetics likely plays a significant role in telomere length and aging,
but, as discussed below, is probably not the most important factor. Robert
Erdmann, Ph.D., (The Amino Acid Revolution, p. 186) says progeria involves
the inability to produce the two enzymes that help keep free radicals in
check: superoxide dismutase (SOD) and glutathione peroxidase (GTP).
Orlock also discusses (p. 101) the cell suicide schedule (research done in
animals that undergo metamorphosis) and the rpr gene which has been dubbed
the "reaper" gene because it appears to be responsible for cell death, and
the "savior" gene that keeps the "reaper" gene suppressed and also plays a
role in helping the cell produce antioxidants. When the savior gene is
turned off in mice they die in infancy or appear to be subjected to
accelerated aging, like the progeria just mentioned in the previous
paragraph.
---------------------------
---------------------------
Cellular aging
Dr. Hayflick is well known for his often cited work that changed the thinking
of gerontologists in the 1960s when he convinced skeptics that his research
was valid that showed that normal cells in tissue culture were not immortal,
but divided only a certain number of times (50 divisions in the cells he
used). This work and work by others indicates the presence of an internal
cellular clock and some work has recently identified the ends of the
chromosomes, called telomeres, as one possible clock mechanism. Cancer cells
which are immortal have an enzyme called telomerase which prevents the ends
of the chromosomes from gradually shortening with each cell division which
eventually is thought to stop cell replication. Dr. Hayflick however does
not believe that aging or death is due to cells not dividing (p. 133).
Serial transplants where cells are repeatedly transplanted from one animal
to a younger animal have shown that cell lifespan can be extended by keeping
it in a "younger environment" so there is some evidence that factors external
to the cells affect their lifespan as well. Cells from progeria and Werner
syndrome patients "age faster than do similar cells taken from age - matched
controls," according to Dr. Hayflick (p. 108).
---------------------------
--------------------------
Robin Holliday in Understanding Ageing, says "It is probable that whitening
of the hair is due to the age - related loss of pigment - forming cells
(melanocytes)." This may be an example of the limited proliferation ability
of some somatic cells, which may mean that some of the "immortalizing"
telomerase enzyme that is present in virtually every type of cancer cell
might be needed in these cells to lengthen the telomeres (the ends of the
chromosome). The enzyme is believed responsible for the immortalization of
cancer cells by preventing the shortening of the telomeres which in normal
cells eventually leads to lack of cell division. Too much of the enzyme
seems to cause immortalization (and often cancer) but if none is present,
the cells eventually loose the chromosome telomeres and the capability to
divide. Genes close to the end of the chromosome are even lost after the
telomeres are lost so if these are important genes, the capability of the
cell to function normally, gradually declines.
It has been found that normal fibroblasts can be transformed by certain
viruses to abnormal cells, like neoplastic cells (cells that form new
tissue). Yet these cells are not immortalized and they are not tumorigenic.
Holliday points out that this "suggests that a barrier does exist that
prevents the emergence of cancer cells" (p. 81). Human B lymphocytes on the
other hand can be readily immortalized by the Epstein - Barr virus, but these
cells appear to remain normal. Research in this area is of course intensive
since cancer is linked this area of research.
---------------------------------
I hope that helps!
Sincerely,
Dennis Fink
