Re: Telomeres

From: Ross A. Finlayson (
Date: Fri Apr 28 2000 - 20:49:52 MDT

Robert J. Bradbury wrote:

> On Fri, 28 Apr 2000, Joao Pedro de Magalhaes wrote:
> I wrote:
> > >Species that do not have long lifespans, such as mice, and farm
> > >animals (bred for fast growth and other qualities, not longevity)
> > >are likely to have different controls on teleomere length and
> > >the length will have different effects vis-a-vis aging.
> >
> > Why? I've read lots of theories claiming telomeres in mice are differently
> > regulated than in humans (which appears to be likely) but I'm ignorant
> > regarding cows' telomeres. You just base your opinion on the fact that cows
> > live less than us or do you know something I don't?
> To start with mice have longer telomeres than humans. So their
> shortening with cell division presumably does not impact much
> on their rate of aging. The longer telomeres *may* explain why
> they get cancer after only 2-3 years with many fewer cell
> divisions (lower mass).
> The original "proto-cell" had to have telomerase on (at some point)
> to keep the telomeres intact from generation to generation. The original
> proto-mammals it is believed were small (more like mice), so they
> probably had short lifespans (almost all small animals do) and like
> mice had little need for anti-cancer programs. Depending on the size
> and longevity of the mammal that was the common ancestor of cows, sheep
> and humans would determine how much of the telomere regulation program
> we share. My suspicion would be that that ancestor would be toward
> the small size for mammals, so there is likely to be a fair amount of
> divergence between the telomere regulation programs.
> Since most cows and sheep are slaughtered before they get old there
> would be little selection for anti-cancer programs in their genomes.
> Probably some research would need to be done on their ancestors to
> determine what selection effects there might have been in their
> environments, but since they are herbivores, I suspect the carnivores
> would be taking them out at the earliest sign of "aging" and that
> would seem to suggest little opportunity for anti-cancer programs
> to get selected.
> Humans, elephants and whales on the other hand all go to the top
> of their environmental niches allowing nature to push on their
> longevity to maximize reproduction. That implies a very careful
> tuning of the anti-cancer program so cancer doesn't kill you before
> all of the other factors. As Cutler, Perls, etc. have pointed out to
> me, the interesting thing about the oldest-old is their ability
> to age "uniformly". In humans the collection of anti-aging programs
> have been pushed farther than most other species.
> I do not doubt that sheep and to a greater extent cows, may have
> some telomere related anti-cancer/pro-longevity balancing occuring
> but I doubt it is as sophisticated as the program in the other species
> I've mentioned. We will know much more when the genomes are done
> and we can compare the regulatory regions for the genes involved
> in controlling telomere length.
> >
> > >Telomere length is fundamentally an anti-cancer control mechanism.
> >
> > Perhaps but I won't bet my money on it yet (and although that might be true
> > in humans, it's unlikely to be the case in many other species such as
> > lobsters or even sharks).
> Perhaps I should have said "Telomere length in humans".
> As you point out, cross-species comparisons are going to be a swamp.
> Sharks are a classic case (very old, very different evolutionary path)
> where the anti-cancer program is likely to be very different.
> >
> > Cloning experiments are useful for they contradict in many ways the theory
> > of DNA accumulating mutations (this particular experiment doesn't do that
> > because the cells were "aged" in vitro after being taken from a fetus but
> > other experiments do just that, despite the data no being conclusive).
> >
> I disagree. With the cloning success rates so low, you have no idea
> whether the failures are due to scientific methodology or whether
> you have a situation where only 5% of the cells contain an "intact"
> developmental program.
> In adult organisms, there is going to be *no* selection against mutations
> accumulating in the developmental genes that have already done their
> job and have been turned off. You are only going to select for
> the lack of mutations in housekeeping genes. All the cells that
> have accumulated fatal errors in their housekeeping genes have
> presumably died.
> The cloning experiments *may* be saying something very interesting
> about the DNA mutation theory. The only way I can see to shed some
> light on this will be when we have good DNA polymorphism chips
> that can allow you to measure the "noise" (mutation) level in the genome.
> Then you take 2000 cells, split them, measure the effective mutation
> level in each "clone" at the same time you try to make an organism
> out of them. If the mutation rate (genome noise level) is lower
> in those clones that produce successful organisms, then you
> have a smoking gun for the DNA mutation accumulation theory.
> Robert

Well, I think it can be assumed that every living thing on the planet that is not
a clone is a mutant. That is to say, the rules of natural selection change
constantly, thus from generation to generation different genetic expressions
become more survivable.

If we cannot say "there is proven telomere lengthening through this process in
cows, thus it can be applied to humans", then it is not very long before this is
true. Sooner or later this or another process works on pigs or orangutans, and
before long there will be treatments to enable cells to have a much longer
predetermined lifespan.

As people grow older, there arise other issues that we already see today. One
example is cancer: the longer the lifespan the more time is there for cells to
turn that way. Luckily, there are existant drugs that specifically target only
cancerous cells for apoptosis, or cell death, thus, within ten years cancer could
be removed from humanity. I use the conditional "could" because it depends on
these "cures" for cancer being allowed to be used. Another example is that of
degenerative nervous system diseases, which are probably the largest class after
cancer (and preprogrammed cell multiplication related to telomerase and
telomeres) that afflict humans as they grow older than they ever have before.
That is another area seeing high levels of research. There are other long-term
aging phenomena, I am not an aging expert, and more will become apparent as
people grow older. There are bacterial and viral based diseases and these are
more treatable and curable each day.

So imagine that within twenty years that some humans will be living with expected
lifespans of twice what they are now, say 200 years. Barring largescale
catastrophe, by the time that span has almost passed there will be techniques to
extend that figure to twice that again, and this continues indefinitely.

This very much brings to mind Malthusian dilemna, by the same token, these living
people can be assumed to be productive, increasingly, throughout their long

Many things will change when people start living hundreds or thousands of years.

Ross F.

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