On Fri, 28 Apr 2000, Joao Pedro de Magalhaes 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"
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
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.
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