I wonder why...
Lars Gollub
in telomeres and telomerase in this newsgroup.
Telomeres have proofed to be the resetable
"clock of life" and are also a very important
subject in fighting cancer. Why are so many
people talking about nonsens like stopping
aging, cancer or aids through diets or
something like that? It is very likely that we
will have a real tool for stopping and even
*reversing* aging within the next ten years.
Why is everyone ignoring this interesting
research? Or do the just don't know?
Best regards,
Lars
Brian Manning Delaney
People were very much talking about it when the research first
came out, but now we're waiting for more research (and a few of
us here are conducting research).
Do you have a way to apply the telomerase research to the
cessation of aging? If so, please tell us about it (and inform
us when you have an IPO!).
Best,
Brian.
--
Brian Manning Delaney
email = first initial + hyphen + last na...@uchicago.edu
I still have to live, for I still have to think.
Sum, ergo cogito: cogito, ergo sum. -Nietzsche.
Help me .. tear down my reason. -Trent Reznor, Nine Inch Nails.
Aubrey de Grey
Lars Gollub wrote:
> As far as I know telomerase is inactive in the normal cells of all
> known mamals.
No, that's wrong. It is highly active in many mouse cell types, and
it's also active at low levels in several human cell types.
> If mice cells have active telomerase they should show no
> signs of aging (at least they should have no Hayflick-limit).
Not if something other than telomere shortening causes replicative
senescence of mouse cells.
> Cells with a continous production of telomerase would develope very
> long telomeres.
No, because there are other proteins that regulate the rate of telomere
lengthening and stop telomerase from lengthening for ever.
> Telomeres have proofed to be the resetable "clock of life"
No, of cell division potential. Most of our cells don't divide much;
some, never. Moreover, the ones that do divide a lot are exactly the
ones that express telomerase (see above). It's the non-dividing,
unrenewable cells (such as nerve cells in the brain) which go most badly
wrong as we age.
> It is very likely that we will have a real tool for stopping and even
> *reversing* aging within the next ten years. Why is everyone ignoring
> this interesting research? Or do the just don't know?
We do know about this research. The consensus of specialists in aging
research is that telomere shortening determines the Hayflick limit in
cultured human cells, and may have something to do with it in cultured
mouse cells, but that cell division is too infrequent in the body to give
telomere shortening any chance of playing a role in aging. Mice have
been made which have no telomerase, and they live just as long as normal.
It is possible that mouse and humans age for different reasons, but most
people think that's unlikely.
If you want to learn more about this, I suggest you look at postings to
this group over the years, using Deja News: http://www.deja.com/ Feel
free to ask if you have other questions.
Aubrey de Grey
Lars Gollub
Thanks for your very detailed answer! This discussion is exactly
what I was looking for in this group. :o)
>> As far as I know telomerase is inactive in the normal cells of all
>> known mamals.
>
>No, that's wrong. It is highly active in many mouse cell types, and
>it's also active at low levels in several human cell types.
Well, my knowledge bases on books and articels which are at
least two years old. Obviously I am not up to date. If telomerase
is active low in several human cells it could explain the very
high Hayflick-limit of some cell groups. (Like blood building cells
which have to divide very often.)
>> If mice cells have active telomerase they should show no
>> signs of aging (at least they should have no Hayflick-limit).
>
>Not if something other than telomere shortening causes replicative
>senescence of mouse cells.
Agreed. I was blinded by the experiments in which adding telomerase
expanded the Hayflick-limit of the cells immensly. I did not take into
account that other aging factors may be *more* limiting than the
length of the telomeres.
>> Cells with a continous production of telomerase would develope very
>> long telomeres.
>
>No, because there are other proteins that regulate the rate of telomere
>lengthening and stop telomerase from lengthening for ever.
Wouldn't it be a waste of energy to continously produce telomerase
and than e. g. inhibit or destroy it with other proteins? Controlling the
rate of production (like inhibiting the RNA coding so no protein bio
synthesis can occur) sounds more efficient to me. But I am just doing
a wild guess right here.
>> Telomeres have proofed to be the resetable "clock of life"
>
>No, of cell division potential.
True. (I was just simplifying...) But if your cells can not devide (to
repair the body) you will die. If you are able extend the division
potential of your cells (through telomerase or other possibilities)
you might be able to extend your maximum lifespan.
>Most of our cells don't divide much;
>some, never. Moreover, the ones that do divide a lot are exactly the
>ones that express telomerase (see above). It's the non-dividing,
>unrenewable cells (such as nerve cells in the brain) which go most badly
>wrong as we age.
Well, I can not agree to this point. Most people do not die because their
nervous system break down. I think the common problem is the failure of
one or more organs like heart, lungs, liver, kidneys and so on. All of these
organs are composed of dividing cells. Do I miss something?
>> It is very likely that we will have a real tool for stopping and even
>> *reversing* aging within the next ten years. Why is everyone ignoring
>> this interesting research? Or do the just don't know?
>
>We do know about this research. The consensus of specialists in aging
>research is that telomere shortening determines the Hayflick limit in
>cultured human cells, and may have something to do with it in cultured
>mouse cells, but that cell division is too infrequent in the body to give
>telomere shortening any chance of playing a role in aging. Mice have
>been made which have no telomerase, and they live just as long as normal.
>It is possible that mouse and humans age for different reasons, but most
>people think that's unlikely.
Yes, it would be unlikely. On the other hand this year a medical treatment
was able to help children with progeria. This medical treatment bases
on the lengthening of the telomeres of the children and it is working.
This proofs that progeria is caused by the absence of telomeres (or
telomerase). This sounds to me like aging *is* different for mice and
humans. Mice may live with telomerase, humans don't.
>If you want to learn more about this, I suggest you look at postings to
>this group over the years, using Deja News: http://www.deja.com/
I already tried Deja News (of course) and found only very few articels.
Searching the net for this topic seems to be very fruitless.
Let me add that I have some problems with the technical terms of
this topic. (Normal and even some technical dictionaries are nearly
useless). I hope I was able to express my thoughts.
>Feel
>free to ask if you have other questions.
Thanks! I am looking forward to the reply to this posting. :o)
>Aubrey de Grey
Lars Gollub
>People were very much talking about it when the research first
>came out, but now we're waiting for more research (and a few of
>us here are conducting research).
Lucky them who are able to do research in this very interessting
direction. I am just a graduated engineer who's interests are
running wild. :o)
>Do you have a way to apply the telomerase research to the
>cessation of aging?
Yes, I think so. (See my reply to Aubrey's posting). But my
knowledge seems to be out of date. If there is something
special you would like to ask about the things I read please
feel free to ask.
>If so, please tell us about it (and inform
>us when you have an IPO!).
Sorry, I do not know what IPO means. Could you please explain?
>Best,
>Brian.
>
>I still have to live, for I still have to think.
I like that! :o) Talking to people who do not want to stop their
aging I am asking this question: "Aren't you curious (what's
to come)?"
Best regards,
Lars
G EddieA95
>organs are composed of dividing cells.
Human beings who develop "bad hearts" do not do so because the heart muscle
wears out; usually it is because of ischemic damage due to blocked coronary
arteries, that starve the heart of oxygen.
IIRC, cardiac (heart) muscle is nonregenerable, and so such ischemic damage
cannot be healed.
GEA
AARL Lab Team
AntiAging Medicine and Longevity Sciences. Visit us each week for updates.
Lars,
IPO stands for "initial public offering" and it relates to when a company
offers shares of their stock to the public. Many biotechnology companies
offer shares of stock in an "initial public offering" to raise money for
research or other needs.
The first company to solve the telomere problem will have shares of stock
that will be worth quite a bit of money and will only increase in value as
their research continues. That is what Brian was talking about when he
mentioned IPO.
Hope this helps.
Harley James
V.P. Information & Research
www.AntiAgingResearch.com - The Weekly Internet Magazine on AntiAging
Medicine and Longevity Sciences. Visit us each week for updates.
Lars Gollub <lars....@home.ins.de> wrote in message
news:7o23jt$r6c$1...@ra.ins.de...
> Hello Aubrey!
>
> Thanks for your very detailed answer! This discussion is exactly
> what I was looking for in this group. :o)
>
> >> As far as I know telomerase is inactive in the normal cells of all
> >> known mamals.
> >
> >No, that's wrong. It is highly active in many mouse cell types, and
> >it's also active at low levels in several human cell types.
>
>
> Well, my knowledge bases on books and articels which are at
> least two years old. Obviously I am not up to date. If telomerase
> is active low in several human cells it could explain the very
> high Hayflick-limit of some cell groups. (Like blood building cells
> which have to divide very often.)
> [snip]
Lars Gollub
>AntiAging Medicine and Longevity Sciences. Visit us each week for updates.
>
>Lars,
Hi!
>IPO stands for "initial public offering" and it relates to when a company
>offers shares of their stock to the public. Many biotechnology companies
>offer shares of stock in an "initial public offering" to raise money for
>research or other needs.
I see. Thanks!
>The first company to solve the telomere problem will have shares of stock
>that will be worth quite a bit of money and will only increase in value as
>their research continues.
Well, at least there will be a wide market for the final treatment. And
people
will sell everything (including grandmas) to get it! :o)
>That is what Brian was talking about when he
>mentioned IPO.
>
>Hope this helps.
>
>Harley James
>V.P. Information & Research
>www.AntiAgingResearch.com - The Weekly Internet Magazine on AntiAging
>Medicine and Longevity Sciences. Visit us each week for updates.
------ssssssnip-----------------
Tom Matthews
> Most people do not die because their
> nervous system break down. I think the common problem is the failure of
> one or more organs like heart, lungs, liver, kidneys and so on. All of these
> organs are composed of dividing cells. Do I miss something?
Not hearts, which are mostly composed of non-dividing muscle cells.
However, the other organs do not 'die' because they run out of
replicative potential either.
In any case, much death in old age is due to cancer and compromised
immunity which is a whole different question and is probably not (except
for aids) related to telomere shortening.
--Tom
Tom Matthews
The LIFE EXTENSION FOUNDATION - http://www.lef.org - 800-544-4440
A non-profit membership organization dedicated to the extension
of the healthy human lifespan through ground breaking research,
innovative ideas and practical methods.
LIFE EXTENSION MAGAZINE - The ultimate source for new
health and medical findings from around the world.
Lars Gollub
>Lars Gollub wrote:
>
>> Most people do not die because their
>> nervous system break down. I think the common problem is the failure of
>> one or more organs like heart, lungs, liver, kidneys and so on. All of
these
>> organs are composed of dividing cells. Do I miss something?
>
>Not hearts, which are mostly composed of non-dividing muscle cells.
>However, the other organs do not 'die' because they run out of
>replicative potential either.
>
>In any case, much death in old age is due to cancer and compromised
>immunity which is a whole different question and is probably not (except
>for aids) related to telomere shortening.
I wonder... what Michael Fossel (author of "Reversing Human Aging")
would have to say to your statement (which I do not doubt)?
Aubrey de Grey
Lars Gollub wrote:
> If telomerase is active low in several human cells it could explain
> the very high Hayflick-limit of some cell groups. (Like blood building
> cells which have to divide very often.)
Yes. The regulation appears to be very precise, because these cells
do show telomere shortening during human aging, but not enough to get
into replicative difficulties.
The immune system is the one which currently looks most as though it
might decline partly because of replicative senescence. But even
there the evidence is uncertain -- for example, the relevant cells
do express telomerase.
> Wouldn't it be a waste of energy to continously produce telomerase
> and than e. g. inhibit or destroy it with other proteins?
Quite right -- though even in mouse cells (and, of course, sperm and
egg cells of all species) the amount of telomerase is a tiny fraction
of total protein synthesis. But it is very normal for cells to have
lots of checks and balances to ensure that important systems work
correctly, even if some components (such as regulating telomerase
production) go wrong.
> But if your cells can not devide (to repair the body) you will die.
Sure -- eventually. There is absolutely no dispute that if we were
to fix everything else that goes wrong, but our telomeres were still
getting shorter in those cells which need to divide, we would die of
that, at some point. But that's of no importance until we DO fix
those other things.
> Most people do not die because their nervous system break down.
That's not really right. Neurodegeneration is a very common cause of
death, and muscle weakness in old age (which leads to falls, which
lead to death from complications) is caused mainly by decline of motor
> I think the common problem is the failure of one or more organs like
> heart, lungs, liver, kidneys and so on. All of these organs are
> composed of dividing cells.
No, the heart and lungs and kidney are all mainly composed of cells
that do not divide (some of them can't, some of them can but hardly
ever actually do.) The average liver cell divides about once a year,
but the liver is a fine example of what I meant -- it's an organ that
suffers virtually no functional decline during aging. People who die
of liver failure do so because they drank an incredible amount or got
a disease. The single most common cause of death in most developed
countries is cardiovascular disease (heart attacks and stroke, mainly)
which result from unrecycled cells in the artery wall that are doing
an important job (soaking up oxidised fat in the blood) but eventually
can't do it well enough.
> this year a medical treatment
> was able to help children with progeria. This medical treatment bases
> on the lengthening of the telomeres of the children and it is working.
> This proofs that progeria is caused by the absence of telomeres (or
> telomerase).
Please tell us what study you're referring to. If you don't have a
primary reference that's OK, just tell us anything you know (where the
research was done, who did it, what sort of progeria, etc.)
> I already tried Deja News (of course) and found only very few articels.
Then you didn't search it very well :-) Seriously, I've been reading
this group for a couple of years and I can assure you that these topics
have been discussed very thoroughly.
> Let me add that I have some problems with the technical terms of this
> topic. (Normal and even some technical dictionaries are nearly useless).
> I hope I was able to express my thoughts.
You're doing fine. "Blood building cells" is just as intelligible as
"hematopoietic stem cells".
Aubrey de Grey
Lars Gollub
First let me thank you for your patience! Looking for a discussion
I got me a full scale course in biology and aging. :o))) Some
things I read (from highly decorated scientists) and many things
I learned in school seem to be just flat wrong. (Or to put it
a less dramatic way: out of date)
>> If telomerase is active low in several human cells it could explain
>> the very high Hayflick-limit of some cell groups. (Like blood building
>> cells which have to divide very often.)
>
>Yes. The regulation appears to be very precise, because these cells
>do show telomere shortening during human aging, but not enough to get
>into replicative difficulties.
This is perfect: It protects the body of developing cancer and does not
shorten the life span of the body which is determined by other factors.
>The immune system is the one which currently looks most as though it
>might decline partly because of replicative senescence. But even
>there the evidence is uncertain -- for example, the relevant cells
>do express telomerase.
Is there proof that cells which do express telomerase do it all the
time or is there a possibility that these relevant cells cease to
produce (enough) telomerase after a while so they get into replicative
difficulties?
And what about various types of human cells taken from the body and
put in a environment with telomerase or telomerase inducing chemicals.
Do they show a Hayflick limit?
----sssnip-------
>> But if your cells can not devide (to repair the body) you will die.
>
>Sure -- eventually. There is absolutely no dispute that if we were
>to fix everything else that goes wrong, but our telomeres were still
>getting shorter in those cells which need to divide, we would die of
>that, at some point. But that's of no importance until we DO fix
>those other things.
I was a little bit disapointed (well, not exactly "a little") when I
realized that telomerase is not the fountain of youth (in contrast to
nearly everything I read so far). But now I see it as an important
part of the whole puzzle and it is good that "we" know about it.
>> Most people do not die because their nervous system break down.
>
>That's not really right. Neurodegeneration is a very common cause of
>death, and muscle weakness in old age (which leads to falls, which
>lead to death from complications) is caused mainly by decline of motor
If muscle weakness is caused by the lack of signal strength (or even
incorrect signals) from the nervous system (yes, I know that signal
strength is expressed through the rate of impulses), this problem could be
solved through the technology of attaching neurons to silicon structures
and a bunch of implanted signal processors. From the view of an engineer
I like this idea but of course this is only a modern version of a
crutch. (Metaphorically speaking. I am refering to the control of the
organs, the glands and so on too.) Just a tool to bypass the time which
is needed to develope a medical treatment for the cause of the problem.
------ssssssssnip--------
>> this year a medical treatment
>> was able to help children with progeria. This medical treatment bases
>> on the lengthening of the telomeres of the children and it is working.
>> This proofs that progeria is caused by the absence of telomeres (or
>> telomerase).
>
>Please tell us what study you're referring to. If you don't have a
>primary reference that's OK, just tell us anything you know (where the
>research was done, who did it, what sort of progeria, etc.)
You got me there. I have to admit that I saw it in a science magazin
on television. There was a german scientist of a (german?) pharma con
speaking about their developement. I can't remember what pharma con
it was and searching the net for a treatment for progeria didn't help
either. At least I remember the sort of the progeria: It was the
Hutchinson-Gilford Progeria Syndrome. The scientist said that they have
conducted the first human tests with very positive results and want to
finish the research in the early next year. Then it was said that
it will take about 5 more years to get it on the market.
Another interessting thing I saw on television was about the cloned
sheep Dolly. It was said that it is "aging rapidly" and that it is
"biological older than it should be". There was no reason given. This
sounds to me to be an problem of short telomeres because only the DNA
of the original sheep was transported in a fresh egg cell of a donator
sheep. As far as I know there were no extra chromosical factors (right
term? I can't imagine.) transported. Isn't it amazing how things seem
to be linked together?
>> I already tried Deja News (of course) and found only very few articels.
>
>Then you didn't search it very well :-) Seriously, I've been reading
>this group for a couple of years and I can assure you that these topics
>have been discussed very thoroughly.
My mistake was to look for "telomeres" which gave me only about 40 hits
(of more or less uninteressting articles). Entering "telomerase" finally
showed me the articles of this newsgroup you were refering to. :o))
---------sssssssnip---------
Best regards,
Lars
Aubrey de Grey
Lars Gollub wrote:
> First let me thank you for your patience!
No problem. Most of us who do research into human aging are very aware
of the importance that the general public attach to our work, and also
of the rather pitiful job that the media do in communicating it. Many
biogerontologists therefore spend time trying to get the science across
themselves, such as by writing popular science books. My type of work
lends itself easily to contributing to Usenet, so that's what I do.
> Is there proof that cells which do express telomerase do it all the
> time or is there a possibility that these relevant cells cease to
> produce (enough) telomerase after a while so they get into replicative
> difficulties?
I know of no evidence that rapidly-proliferating cells produce less
telomerase in later life. It might even be that they produce a bit
more, so as to stave off replicative senescence. But the levels they
express are at the limit of detectability (with current technology),
so it's a hard thing to measure.
> And what about various types of human cells taken from the body and
> put in a environment with telomerase or telomerase inducing chemicals.
> Do they show a Hayflick limit?
Mostly, no. Geron have introduced telomerase into about ten different
cell types last I heard, none of which have yet exhibited any Hayflick
limit. There is one cell type, keratinocytes, which other labs have
given telomerase and they still show replicative senescence, but last
I heard Geron have not yet tried with keratinocytes but they are going
to, to see whether the difference is in the cells or in the details of
the experimental technique.
> I was a little bit disapointed (well, not exactly "a little") when I
> realized that telomerase is not the fountain of youth (in contrast to
> nearly everything I read so far).
Hm. That's what I meant about the media. It's a simple and seductive
idea, so it's easy to make a TV programme or a magazine article about
it that will get lots of attention and make money.
> But now I see it as an important
> part of the whole puzzle and it is good that "we" know about it.
Sure. Also, technology to keep cells capable of a lot of division has
masses of other biotechnological and medical applications. It's hugely
valuable work, don't get me wrong.
> There was a german scientist of a (german?) pharma con
> speaking about their developement. I can't remember what pharma con
> it was and searching the net for a treatment for progeria didn't help
> either. At least I remember the sort of the progeria: It was the
> Hutchinson-Gilford Progeria Syndrome. The scientist said that they have
> conducted the first human tests with very positive results and want to
> finish the research in the early next year. Then it was said that
> it will take about 5 more years to get it on the market.
OK. It has indeed been known for some time that H-G sufferers have
short telomeres (Allsopp, Proc Natl Acad Sci USA 89:10114). However,
this study looked at skin fibroblasts, which hardly ever divide in
the body during adulthood (thugh they do divide before that, while
the skin is growing) and which are now agreed to show no telomere
shortening whatsoever during adulthood (Cristofalo, Proc Natl Acad
Sci USA 95:10614), though again they do shorten in childhood. I don't
know of any study of telomere length in H-G in cells which do divide
a lot (and whose telomeres get shorter during life, even in normal
people). Thus there are two possibilities: either H-G sufferers lose
telomere length faster than us in those rapidly dividing cell types,
or they start off with very short telomeres and suffer problems late
in development as a result. [The second possibility is what seems to
happen with mice who are bred so as to have no telomerase but also to
begin (as the fertilised egg) with extremely short telomeres: they
have numerous problems (including a shortened lifespan), but they're
not normal mice. See Rudolph, Cell 96:701.] But either way, the
presence of short telomeres is suggestive that telomerase induction
would be a therapy. The problem is that H-G only resembles some of
the aspects of aging -- perhaps the ones that would be left if we had
fixed everything else except telomere shortening. And to make matters
worse, even the fact that H-G and aging have things in common at the
macroscopic level is no reason to believe that those things are caused
by the same molecular process in H-G as in normal aging.
> Another interessting thing I saw on television was about the cloned
> sheep Dolly. It was said that it is "aging rapidly" and that it is
> "biological older than it should be". There was no reason given. This
> sounds to me to be an problem of short telomeres because only the DNA
> of the original sheep was transported in a fresh egg cell of a donator
> sheep.
Yes, this made a lot of news recently. The telomere analysis of Dolly
was published about two months ago in Nature 399:316. But nothing has
yet been reported to suggest that there are ANY consequences of this
for Dolly's lifespan, susceptibility to age-related diseases, etc, and
the article took pains to end with "it remains to be seen whether a
critical length will be reached during the animal's lifetime". That
didn't stop the media though -- do an AltaVista search for "telomeres
AND dolly" and you'll see what I mean.
Aubrey de Grey
Rodney Reid
Lars Gollub <lars....@home.ins.de> wrote in message
news:7o23jt$r6c$1...@ra.ins.de...
>
> >Most of our cells don't divide much;
> >some, never. Moreover, the ones that do divide a lot are exactly the
> >ones that express telomerase (see above). It's the non-dividing,
> >unrenewable cells (such as nerve cells in the brain) which go most badly
> >wrong as we age.
>
>
> Well, I can not agree to this point. Most people do not die because their
> nervous system break down. I think the common problem is the failure of
> one or more organs like heart, lungs, liver, kidneys and so on. All of
these
> organs are composed of dividing cells. Do I miss something?
>
There are nerves which control the beating of the heart, the breathing of
lungs, etc. etc. that do go 'bad'; if the vagus nerve doesn't function
properly, you are likely to have a heart attack
There's other problems with waste accumulation that's not removed by the
body - plaque in arteries is a common one.
Another area which could pose a problem when/if we ever can stop telomere
shortening is the immune system and auto-immune disorders (prostate,
rheumatoid arthritis, etc.)
Doesn't mean these problems won't be eventually solved, it just means
telomeres on their own won't solve the problem.
...Rodney
Tom Matthews
>
> Lars Gollub wrote:
> > Another interessting thing I saw on television was about the cloned
> > sheep Dolly. It was said that it is "aging rapidly" and that it is
> > "biological older than it should be". There was no reason given. This
> > sounds to me to be an problem of short telomeres because only the DNA
> > of the original sheep was transported in a fresh egg cell of a donator
> > sheep.
>
> Yes, this made a lot of news recently. The telomere analysis of Dolly
> was published about two months ago in Nature 399:316. But nothing has
> yet been reported to suggest that there are ANY consequences of this
> for Dolly's lifespan, susceptibility to age-related diseases, etc, and
> the article took pains to end with "it remains to be seen whether a
> critical length will be reached during the animal's lifetime". That
> didn't stop the media though -- do an AltaVista search for "telomeres
> AND dolly" and you'll see what I mean.
The importance of this fact just hit me!
If we could create a cohort of Dollys (animals with initially shortened
telomeres but otherwise the same as normal) and found that their maximum
lifespan was identical to controls (those without initially shortened
telomeres) this would be very solid support for the contention that
telomere shortening does not normally have any effect on maximum
lifespan and, thus, that telomerase research should not be the initial
or highest priority of anti-aging research.
IMO, this needs to be done immediately with several species types to
settle this question about the effect of telomere shortening on species
maximum lifespan (and by extrapolation from the right species, strongly
on human lifespan). Then, we would have the necessary ammunition to
divert some of the funding being spent on telomerase research for
anti-aging purposes, to where it will do the most good. Ie towards the
things which *are* currently limiting maximum lifespan.
Aubrey de Grey
Tom Matthews wrote:
> If we could create a cohort of Dollys (animals with initially shortened
> telomeres but otherwise the same as normal) and found that their maximum
> lifespan was identical to controls (those without initially shortened
> telomeres) this would be very solid support for the contention that
> telomere shortening does not normally have any effect on maximum
> lifespan and, thus, that telomerase research should not be the initial
> or highest priority of anti-aging research.
This is exactly the experiment I keep banging on about with the knockout
mice. They weren't cloned, but they had their initial telomere length
shortened by breeding successive generations in the absence of telomerase.
And, indeed, for five generations there was exactly zero effect on the
mean or maximum lifespan. Only in generation six, when the telomeres at
fertilisation were so short that the mice were never fertile and had lots
of other problems with highly proliferative tissues, was there any impact
on lifespan. Here are the major references again:
Blasco MA et al, Cell 1997 Oct 3;91(1):25-34
Lee HW et al, Nature 1998 Apr 9;392(6676):569-574
Rudolph KL et al, Cell 1999 Mar 5;96(5):701-712
> IMO, this needs to be done immediately with several species types to
> settle this question about the effect of telomere shortening on species
> maximum lifespan (and by extrapolation from the right species, strongly
> on human lifespan).
Right. The problem here is that no short-lived species can be considered
as a "right species". I'm not sure Tom Mahoney has come round to this
view yet, but bulk of the telomeres-in-aging community now accept that
mice don't age by telomere shortening, but that primates still may. The
evidence for this is exactly 0, but so is the direct evidence against it.
Aubrey de Grey
Lars Gollub
Hi Rodney!
>There are nerves which control the beating of the heart, the breathing of
>lungs, etc. etc. that do go 'bad'; if the vagus nerve doesn't function
>properly, you are likely to have a heart attack
No doubt here, but I didn't realize that this is a common problem.
>There's other problems with waste accumulation that's not removed by the
>body - plaque in arteries is a common one.
Isn't it true, that the waste is eliminated when people are young? So the
waste accumulation ins't the problem, the stopped elimination of the waste
is it. That leads to "How to reactivate it?". Is that right? Or does waste
accumulation starts at the stage of a fetus?
>Another area which could pose a problem when/if we ever can stop telomere
>shortening is the immune system and auto-immune disorders (prostate,
>rheumatoid arthritis, etc.)
Yes, the causes for that have to be found too. The nanotech would be a
great technology for replacing the natural immune system with an artifical
one. If the knowledge of your artifical immune system could be exchanged
with the immune system of everybody else on the world (e.g. through your
PC and the Internet) you would get *one globel immune system*. :o)
But that stuff is at least 20 years ahead... I hope that at that point the
our natural immune system is completly under control of us. Maybe a
artificial one is not neccessary or you can communicate with your natural
immune system or or or.... :o)
>Doesn't mean these problems won't be eventually solved, it just means
>telomeres on their own won't solve the problem.
But if we can controll all other factors, the control would be useless
without
the control over the telomeres. And vice versa. It's just a piece of the
puzzle,
a part of the whole key.
Knowing how to manipulate the telomeres could be very important
for other medical technologies. (e. g. cloning) These technologies might
be able to help some of us to get old enough to participate in newer
techniques. Of course other fields would benefit of advanced cloning too.
(Just some thoughts)
>...Rodney
Best regards!
Lars
Lars Gollub
-----------sssssssssnip--------------
>The importance of this fact just hit me!
>
>If we could create a cohort of Dollys (animals with initially shortened
>telomeres but otherwise the same as normal) and found that their maximum
>lifespan was identical to controls (those without initially shortened
>telomeres) this would be very solid support for the contention that
>telomere shortening does not normally have any effect on maximum
>lifespan and, thus, that telomerase research should not be the initial
>or highest priority of anti-aging research.
Do you think that money is *wasted* on telomerase research? I could
not fully agree to such statement because (if I understand everything
correctly) the telomeres are not the limiting factor but *will become*
the limiting factor if we increase lifespan a little bit (or more). I fully
agree with you that it should not be on top priority! If it is unclear
what limits lifespan resources should be split up equally under the
research of the most likely causes.
>IMO, this needs to be done immediately with several species types to
>settle this question about the effect of telomere shortening on species
>maximum lifespan (and by extrapolation from the right species, strongly
>on human lifespan). Then, we would have the necessary ammunition to
>divert some of the funding being spent on telomerase research for
>anti-aging purposes, to where it will do the most good. Ie towards the
>things which *are* currently limiting maximum lifespan.
Do you have any ideas what this could be? Is there a favorite cause
discussed in science?
>--Tom
>Tom Matthews
Best regards,
Lars
Tom Matthews
>
> Hello Tom!
>
> -----------sssssssssnip--------------
> >The importance of this fact just hit me!
>
> >
> >If we could create a cohort of Dollys (animals with initially shortened
> >telomeres but otherwise the same as normal) and found that their maximum
> >lifespan was identical to controls (those without initially shortened
> >telomeres) this would be very solid support for the contention that
> >telomere shortening does not normally have any effect on maximum
> >lifespan and, thus, that telomerase research should not be the initial
> >or highest priority of anti-aging research.
>
> Do you think that money is *wasted* on telomerase research?
Not at all!
No money spent on biological research which produces publishable results
is *wasted*.
But we are all slowly dying!
The priority should be to spend the money in the best way possible to
increase the average age of death.
> I could
> not fully agree to such statement because (if I understand everything
> correctly) the telomeres are not the limiting factor but *will become*
> the limiting factor if we increase lifespan a little bit (or more).
That is correct.
For possibly a very few current causes of death (eg aids) they may be
the critical factor.
As maximum lifespan is increased, they will become an important factor
in more deaths.
At some point of maximum lifespan, say, 180 years, they may be the
dominant cause of death.
Our top priority should be to find and eliminate what is currently the
most important age-related cause of death.
> I fully
> agree with you that it should not be on top priority! If it is unclear
> what limits lifespan resources should be split up equally under the
> research of the most likely causes.
I agree.
> >IMO, this needs to be done immediately with several species types to
> >settle this question about the effect of telomere shortening on species
> >maximum lifespan (and by extrapolation from the right species, strongly
> >on human lifespan). Then, we would have the necessary ammunition to
> >divert some of the funding being spent on telomerase research for
> >anti-aging purposes, to where it will do the most good. Ie towards the
> >things which *are* currently limiting maximum lifespan.
>
> Do you have any ideas what this could be? Is there a favorite cause
> discussed in science?
My two current favorites are:
1. mitochondrial theory of aging (Aubrey's specialty) which is related
somewhat to the antioxidant theory but only to antioxidants which will
penetrate mitochondria and make processes there more efficient (very
hard to do, but PBN may work by doing that).
2. the gylcation, AGEs accumulation theory (which is highly related to
the accelerated aging pathologies of diabetics but occurs more slowly,
inexorably and irreversably in all of us. This one is also related to
antioxidants of which a derth can hasten glycation.
Andrew Mason
>> IMO, this needs to be done immediately with several species types to
>> settle this question about the effect of telomere shortening on
species
>> maximum lifespan (and by extrapolation from the right species,
strongly
>> on human lifespan). Then, we would have the necessary ammunition to
>> divert some of the funding being spent on telomerase research for
anti-
>> aging purposes, to where it will do the most good. Ie towards the
things
>> which *are* currently limiting maximum lifespan.
Tom
It sounds like you have already made up your mind before the research
is done. Don’t you think it would be worth remaining a little more
objective and impartial until more results are in?
Telomerase research shows a lot of promise in the treatment (and in
some cases detection) of many diseases. It would be difficult or
impossible to isolate the research that was specifically aimed at anti-
aging, so diverting funding as you suggest would be hard without
setting back overall research.
Aubrey de Grey wrote:
>The problem here is that no short-lived species can be considered as
a "right
>species". I'm not sure Tom Mahoney has come round to this view yet,
but
>bulk of the telomeres-in-aging community now accept that mice don't
age by
>telomere shortening, but that primates still may. The evidence for
this is
>exactly 0, but so is the direct evidence against it.
Aubrey
I have heard that successive cloning of mice also results in problems
at the fifth generation (I don’t have a reference for this so cannot
vouch for its accuracy). This may be similar to the telomerase knockout
mice not displaying viable reproduction by the 5th generation.
The results of Dr. Jean-Paul Renard’s experiments (The Lancet
1999;353:1489-1491 - see abstract below) with creating cloned calves
from cloned adult cattle suggests the possibility that telomeres may be
critically short in cloned cattle by the second generation.
I have still not seen any information of the telomere lengths of
Renard’s calves, but if they were short for their age it may be broadly
analogous to what would happen if telomerase knockout cattle were bred.
I have heard that Dolly the sheep’s telomeres are 20% shorter than they
should be, and would be interested to know whether the cattle telomeres
were similarly short.
If this speculation were shown to be correct it would imply that there
may be a significant difference between the effects on maximum lifespan
of telomere lengths in mice and cattle. Whether or not telomere length
limits maximum lifespan in cattle may be indicated by observing the
life histories of those cloned cattle already alive. If it can be shown
that they do not age prematurely then the case against telomere length
being the lifespan limiting factor in the longer lived mammals would be
strengthened.
One question – what do mice typically die of when they live in a lab
environment? What percentage die of tumors and what percentage die of
aging related ailments?
Andrew Mason
Lymphoid hypoplasia and somatic cloning.
Renard JP, Chastant S, Chesne P, Richard C, Marchal J, Cordonnier N,
Chavatte P, Vignon X
Unite de Biologie du Developpement, INRA, Jouy en Josas, France.
ren...@biotec.jouy.inra.fr
BACKGROUND: Adult somatic cloning by nuclear transfer is associated
with high rate of perinatal mortality but there is still no evidence
that nuclear transfer itself is responsible for these failures. We
report on a longlasting defect linked to somatic cloning. METHODS: Skin
cells grown from an ear biopsy specimen from a 15-day-old calf were
used as a source of nuclei. The donor animal was a clone of three
females obtained from embryonic cells. Clinical examination,
haematological, and biochemical profiles, and echocardiography of the
somatic clone were done from birth to death. FINDINGS: After 6 weeks of
normal development, the somatic cloned calf had a sudden and rapid fall
in lymphocyte count and a decrease in haemoglobin. The calf died on day
51 from severe anaemia. Necropsy revealed no abnormality except thymic
atrophy and lymphoid hypoplasia. INTERPRETATION: Somatic cloning may be
the cause of long-lasting deleterious effects. Our observation should
be taken into account in debates on reproductive cloning in human
beings.
Sent via Deja.com http://www.deja.com/
Share what you know. Learn what you don't.
Aubrey de Grey
Andrew Mason wrote:
> I have heard that successive cloning of mice also results in problems
> at the fifth generation (I dont have a reference for this so cannot
> vouch for its accuracy). This may be similar to the telomerase knockout
> mice not displaying viable reproduction by the 5th generation.
I don't know of this work but I agree, that interpretation is plausible.
(By "generation" I presume you mean successive cloning from clones.)
> The results of Dr. Jean-Paul Renards experiments (The Lancet
> 1999;353:1489-1491 - see abstract below) with creating cloned calves
> from cloned adult cattle suggests the possibility that telomeres may be
> critically short in cloned cattle by the second generation.
Well, only very tenuously. This is a report of a *single* animal that
died of an apparent abrupt failure of haematopoiesis at age 7 weeks.
It is certainly conceivable that death happened because the blood stem
cells somehow received extremely short telomeres and thereby underwent
replicative senescence, but clearly there are many other possibilities.
> I have still not seen any information of the telomere lengths of
> Renards calves, but if they were short for their age it may be broadly
> analogous to what would happen if telomerase knockout cattle were bred.
I don't think the telomere length was measured. I stress, however, that
the problem occurred in a single animal and the report notes that other
clones from the same donor are fit and well.
> Whether or not telomere length
> limits maximum lifespan in cattle may be indicated by observing the
> life histories of those cloned cattle already alive. If it can be shown
> that they do not age prematurely then the case against telomere length
> being the lifespan limiting factor in the longer lived mammals would be
> strengthened.
Yes. Of course the problem is that cattle have a maximum lifespan of
30 years, and we'd like information sooner. See below, though.
> One question what do mice typically die of when they live in a lab
> environment? What percentage die of tumors and what percentage die of
> aging related ailments?
I don't quite understand your question, since tumours are definitely
aging-related. I don't know exact numbers, but tumours are a common
cause of mouse death in the lab.
----------------
The hypothesis that telomere shortening may play a bigger role in long-
lived mammals than in short-lived ones is unattractive in parsimony
terms, but not so much so as to be rejected out of hand in the absence
of data. Therefore it would certainly be valuable to devise a measure
of this in long-lived mammals that can be done more quickly than by
observing life histories of animals that are not yet born.
One approach to this seems to me to be very simple indeed: to determine
telomere length of fibroblasts at death of people who died of aging-
related causes. Clearly the telomere length of fibroblasts is unlikely
to have an actual causative influence on age-related pathologies, but it
is likely to be well correlated to telomere length elsewhere in the body,
because the telomere length in a given cell at a given age is determined
by its length in the zygote and the cell's somatic "life history". So,
people who die of aging-related causes at a relatively early age should
(if telomeres matter in such causes) tend to have rather short fibroblast
telomeres for their age. However, as far as I know this has never been
asked. In fact, rather to my surprise I could not even find a study of
my presumption above that telomere lengths correlate across tissues (i.e.
that people with short fibroblast telomeres have short telomeres in
other tissues too). Perhaps Tom Mahoney knows of one.
Aubrey de Grey
fre...@webtv.net
>No money spent on biological research
>which produces publishable results is
>*wasted*.
>But we are all slowly dying!
>The priority should be to spend the
>money in the best way possible to
>increase the average age of death.
I can think of no field, that is yielding anything close, to that being
obtain in telomerase research. Do the results on research on
mitochondria, or AGE accumulation have such earth shaking advancements,
in the last few years?
We are dying day by day, and Tom I am not but a few years behind you.
Any slow down, in telomerase research, makes death more probable IMHO.
>My two current favorites are:
>1. mitochondrial theory of aging
>(Aubrey's specialty) which is related
>somewhat to the antioxidant theory but
>only to antioxidants which will penetrate
>mitochondria and make processes there
>more efficient (very hard to do, but PBN
>may work by doing that).
>2. the gylcation, AGEs accumulation
>theory (which is highly related to the
>accelerated aging pathologies of
>diabetics but occurs more slowly,
>inexorably and irreversibly in all of us.
>This one is also related to antioxidants of
>which a derth can hasten glycation.
>--Tom
>Tom Matthews
These two areas are all well and good, but, to my way of thinking, they
do not address the underlying cause of aging. It is though we turned
back the clock, to the 70s and 80s, and were discussing free radicals
again. While I have worked very hard to slow free radical damage, it is
not the answer.
I have included this link to a recent interview, with two of the
telomerase researchers. If anything it gives a glimpse of the future
possibilities, with this brand new technology.
Every system of our bodies is breaking down day after day, and this IS
the problem. Telomerase may not be the total answer, but it looks like
it has the most potential answers.
If the telomerase gene, in each cell of our bodies, was activated, then
it would make a big difference, and yes I realize that cancers may also
spring up, if the cells were already going in that direction.
If you look at the money spent on heart disease, cancer and arthritis
research, then that money spent on telomerase research, then you see the
very real problem.
Yes I know I am crazy<G>, but I just felt I had to say something on this
issue. It is a matter of life or aging, to me as well.---Dwight
http://www.discover.com/june_99/immortal.html
Aubrey de Grey
Dwight wrote:
> I can think of no field, that is yielding anything close, to that
> being obtain in telomerase research. Do the results on research on
> mitochondria, or AGE accumulation have such earth shaking advancements,
> in the last few years?
Actually, advances in the last few years have brought AGE accumulation
closer than telomere shortening to being reversed in vivo. See Vasan
et al, Nature 382:275-278 and postings here discussing Alteon. The
scandalous thing is that Alteon are having real trouble getting ALT-711
through clinical trials, not because of any doubts about its efficacy
but because it (or its suspected active site) is so simple a chemical
that big pharmaceutical companies reckon its patent is not worth much
(i.e. someone could probably rather easily create a similar chemical
that worked the same way but evaded the patent), so they won't put in
the required capital. I have the above from a senior scientist at one
of the several big pharmaceutical firms which have looked at ALT-711,
who was personally involved in his firm's decision not to fund it; he
sees no effective way out for them.
The relevant manipulations of mitochondria are harder than they were
for telomerase. When they're achieved, we'll see what their effects
on aging are. Till then, we're not in a position to judge.
The question, of course, is not whether such-and-such a field has made
earth-shaking advances but how important those advances are to life
extension.
> These two areas are all well and good, but, to my way of thinking, they
> do not address the underlying cause of aging. It is though we turned
> back the clock, to the 70s and 80s, and were discussing free radicals
> again. While I have worked very hard to slow free radical damage, it is
> not the answer.
This is a very common argument and I think it is worth spending a few
sentences to explain why it is wrong. When an attempt to retard the
rate of aging fails, we learn almost exactly nothing: all we know is
that we haven't found the right intervention. The fact that we have
not succeeded in slowing aging with antioxidants could just as well be
because the antioxidants aren't getting to the right places as because
oxidative damage doesn't matter. Only if the intervention succeeds
are we any the wiser. But that's not the end of the story, because
a completely symmetrical logic exists for interventions designed to
ACCELERATE aging, such as by depleting antioxidants or telomerase or
whatever. In this case, we learn almost nothing if we succeed (i.e. if
the animal dies young), because it is very easy to shorten lifespan.
But we learn hugely valuable information if the intervention fails --
if lifespan is unaffected -- because it means that the thing we have
interfered with is irrelevant to aging during a normal lifespan of the
organism that we tested. This is why the telomerase knockout mice
are so valuable. I remind everyone that there are also knockout mice
for the three isoforms of superoxide dismutase (mitochondria, cytosolic
and extracellular), and that the mitochondrial knockouts die a few days
after birth (uninformative) but the cytosolic and extracellular ones are
fit and healthy and have no significant reduction of lifespan (vastly
informative). This shows that the exact location that an antioxidant
gets to matters a great deal, and adds to the plausibility of the view
that oxidative damage is the main cause of aging but the antioxidants
we've tried so far aren't getting to the right places.
> I have included this link to a recent interview, with two of the
> telomerase researchers
> http://www.discover.com/june_99/immortal.html
Thank you for posting this link. As usual, these two very prominent and
responsible researchers (Harley and Shay) have said almost nothing that
is in doubt but have been quoted under a headline that says something
completely different -- in this case, that telomerase induction may be
the end of clogged arteries. (I don't say they're ENTIRELY blameless,
but they have the funding of their research to think of so I can excuse
them for allowing overinterpretations to go uncorrected.) What Harley
is actually quoted as saying is that endothelial cells become less able
(with age) to proliferate to re-line an artery after angioplasty. He
doesn't even say that this is due to telomere shortening in those cells
(which is good, because there is no evidence that that is the cause: it
may be an effect of other aspects of their aging, or even of aging of
other cells which may increase oxidative stress in the circulation).
The discussion of skin is similar: the text says that overproduction of
collagenase by replicative senescent dermal fibroblasts is the cause of
wrinkled skin, when neither Harley nor Shay said anything of the kind.
(Which is good, because wrinkled skin is actually caused mainly by the
NON-breakdown of collagen that has become excessively cross-linked, and
the tiny proportion of collagenase-overproducing cells in the skin has
a similarly tiny effect on the skin's overall collagenase levels.)
Sorry to rant...
Aubrey de Grey
fre...@webtv.net
--snip--
>So, people who die of aging-related
>causes at a relatively early age should (if
>telomeres matter in such causes) tend to
>have rather short fibroblast telomeres for
>their age. However, as far as I know this
>has never been asked. In fact, rather to
>my surprise I could not even find a study
>of my presumption above that telomere
>lengths correlate across tissues (i.e. that
>people with short fibroblast telomeres
>have short telomeres in other tissues
>too). Perhaps Tom Mahoney knows of
>one.
>Aubrey de Grey
A person dying at an earlier age may not have an unusual amount, of
short telomeres. They may have sustained increased DNA damage, with
damage to only specific cell telomeres. Let's say a person suffers
telomeric damage, of the skin cells, from excessive UV light. The
telomeric damage could result in cancer and death, but all other cells
would not have shortened telomeres. If telomerase were present in these
skin cells, than the damage would have been repaired ( I think<G>),
before the genetic change towards cancer could take place. Any pointing
out, errors in my thinking, is gladly appreciated.--Dwight
Aubrey de Grey
Dwight wrote:
> >So, people who die of aging-related
> >causes at a relatively early age should (if
> >telomeres matter in such causes) tend to
> >have rather short fibroblast telomeres for
> >their age.
> A person dying at an earlier age may not have an unusual amount, of
> short telomeres. [Example scenario] Any pointing out, errors in my
> thinking, is gladly appreciated.--Dwight
Absolutely right -- the critical point is "tend to". Certainly it
would not be possible to distinguish on this basis between individual
people whose cause of death was accelerated by short telomeres and
ones where it was irrelevant, but if short telomeres have any effect
-- however indirect or subtle -- on the body's capacity to fend off
aging-related pathologies then SOME of the people who die early will
do so because of short telomeres, so the average telomere length of
those early diers will be less than the average of non-diers of the
same age.
Aubrey de Grey
Tom Matthews
But a very excellent and necessary 'rant'.
All that I want to add to this is:
Even if it were true that telomerase advances are leaping ahead while
research into other causes of aging is getting nowhere (quite reasonable
considering the different levels of promotion, media attention and
funding),
since telomere shortening appears to be the proximate cause of *few
current deaths*, all that research will not help any of us to live any
longer!
We need to find and to research those fundamental factors which
determine the *current* maximum human lifespan.
We also very much need to find ways to demonstrate that these some
factors 'underlie' the major terminal diseases (or not - it is an open
question which I think is true).
If it can be done this demonstration would divert all the billions spent
on those disease into removing the basic causes of aging (certainly
including telomere shortening). Athersclerosis, dimentias, most cancers,
and other diseases contracted mainly by the elderly would then all be
prevented by stopping aging.
Andrew Mason
> Well, only very tenuously. This is a report of a *single* animal that
> died of an apparent abrupt failure of haematopoiesis at age 7 weeks.
> It is certainly conceivable that death happened because the blood stem
> cells somehow received extremely short telomeres and thereby underwent
> replicative senescence, but clearly there are many other
possibilities.
Aubrey
The original article I saw stated -
"Renard and colleagues point out that one other cloned calf born in
their unit died at about the same age after displaying an unusual
inability to fight infection. That calf's death had been complicated by
an injury, however, so the exact reasons for its demise remain unclear."
I appreciate that 2 similar deaths do not prove anything, however it
does make the suggestion of critically short telomeres less unlikely.
Unfortunately this is all speculative until some tests are done on the
telomere lengths in those calves.
> > One question what do mice typically die of when they live in a lab
> > environment? What percentage die of tumors and what percentage die
of
> > aging related ailments?
>
> I don't quite understand your question, since tumours are definitely
> aging-related. I don't know exact numbers, but tumours are a common
> cause of mouse death in the lab.
I was just wondering what percentage of age related deaths in mice were
caused by cancer and what percentage were caused by other ailments.
> The hypothesis that telomere shortening may play a bigger role in
long-
> lived mammals than in short-lived ones is unattractive in parsimony
> terms, but not so much so as to be rejected out of hand in the absence
> of data.
Parsimony is often not favoured in biological systems where genetic
drift and natural selection can result in a wide variety of solutions
to a single problem.
regards
Andrew
fre...@webtv.net
>But a very excellent and necessary 'rant'.
I agree<G>
>All that I want to add to this is:
>Even if it were true that telomerase
>advances are leaping ahead while
>research into other causes of aging is
>getting nowhere (quite reasonable
>considering the different levels of
>promotion, media attention and funding),
>since telomere shortening appears to be
>the proximate cause of *few current
>deaths*, all that research will not help
>any of us to live any longer!
>We need to find and to research those
>fundamental factors which determine the
>*current* maximum human lifespan. We
>also very much need to find ways to
>demonstrate that these some factors
>'underlie' the major terminal diseases (or
>not - it is an open question which I think
>is true).
Tom what do you think our chances really are of getting up to a 110? If
we not find out the source of our aging, then I am afraid that we will
not reach the maximum lifespan.
Telomerase is receiving more money and press, because it is impossible
IMHO. It was impossible to immortalize human cells just a few years ago,
according to most of the scientific community. They said if telomerase
were to be added, then it would have no effect on the lifespan of the
cells. They also said that, if by chance it could be done
(immortalization), then the cells would become cancerous. The only big
point, which is not in favor of it, are the knock out mice. Most of the
evidence, that we are finding, does point in that direction.
Money is still being spent on other research, and it may buy us some
more time, but the telomerase research should fall one way or another
very quickly. In the mean time, we take our nutrients.
>If it can be done this demonstration
>would divert all the billions spent on
>those disease into removing the basic
>causes of aging (certainly including
>telomere shortening). Athersclerosis,
>dementias, most cancers, and other
>diseases contracted mainly by the elderly
>would then all be prevented by stopping
>aging.
>--Tom
>Tom Matthews
I believe many of these diseases will fall, to new effective treatments,
in the next few years. This will shift money and manpower over, to the
question of aging. We have the baby boomers, which I am one<G>, who are
headed for social security, and the government will throw even more
money, into the solving the medical problem of aging. I don't mind
death, but aging is the pits<G>--Dwight
Aubrey de Grey
Dwight wrote:
> It was impossible to immortalize human cells just a few years ago,
> according to most of the scientific community. They said if
> telomerase were to be added, then it would have no effect on the
> lifespan of the cells. They also said that, if by chance it could
> be done (immortalization), then the cells would become cancerous.
This is absolutely wrong. I can assure you that the only surprise
was the ease with which Geron did what they did, simply because most
experiments take a good deal of fine-tuning before they work. The
central role of telomere shortening as the mediator of replicative
senescence has been accepted for many years. As to cancer, likewise,
no one ever said that cancer would be caused by telomerase, only (as
Shay explains in the Discover article you mentioned) that it would
make human (but not mouse) cells less well defended against cancer.
This is still the general view, and there is no new evidence against
it -- the only relevant study involved growing telomerase-positive
human cells in a mouse and noting that they didn't become cancerous
in the duration of the study, which was only two months. (See Nature
Genetics 21:111-114.) The absence of cancer for two months in a
population of only a few million cells does not prove that the cells
are no more prone to cancer than telomerase-negative cells, and no
one in the telomere research community claims that it does prove that.
> The only big point, which is not in favor of it, are the knock out
> mice. Most of the evidence, that we are finding, does point in that
> direction.
No, this is not how science is done. If a hypothesis is true it is
always true, so evidence against a hypothesis has to be shown to be
methodologically flawed before it can be ignored. Evidence supporting
a hypothesis is only valuable to the extent that it challenges other
hypotheses. The ability of telomerase to abolish replicative senescence
is not in conflict with any hypothesis of aging (which is a large part
of why it didn't surprise anyone -- see above), so it has no weight.
> >Athersclerosis,
> >dementias, most cancers, and other
> >diseases contracted mainly by the elderly
> >would then all be prevented by stopping
> >aging.
>
> I believe many of these diseases will fall, to new effective treatments,
> in the next few years. This will shift money and manpower over, to the
> question of aging.
This is not a view shared by the biogerontology research community, nor
by many in the broader medical community. Aging makes us progressively
more prone to suffer from those diseases, and so makes it progressively
more difficult for treatments to be effective. The abolition of such
diseases is simply impossible without abolishing aging: new treatments
can only delay the age of their onset.
I do want to support something you wrote previously, though, which is
a view shared by (I hope) everyone here:
> If you look at the money spent on heart disease, cancer and arthritis
> research, then that money spent on telomerase research, then you see
> the very real problem.
If we extend your statement to all anti-aging research, rather than
just telomerase research, then you are absolutely right. The idea that
anti-aging research is (at least in the long term) the most effective
form of anti-disease research is something that we have so far failed
to impress on the medical community (let alone the sources of funding).
If we could get that across, the pace of progress would be very different.
Aubrey de Grey
Aubrey de Grey
> The original article I saw stated -
> "Renard and colleagues point out that one other cloned calf born in
> their unit died at about the same age after displaying an unusual
> inability to fight infection. That calf's death had been complicated
> by an injury, however, so the exact reasons for its demise remain
> unclear."
Yes, C R Acad Sci III 1998;321(9):735-745 cited in the Lancet article.
> I appreciate that 2 similar deaths do not prove anything, however it
> does make the suggestion of critically short telomeres less unlikely.
Heh - one could equally argue the opposite, because this was a separate
experiment (different donor tissue, different donor age) that also gave
rise to other clones that did not show problems. But I agree, telomere
measurements would be nice.
> I was just wondering what percentage of age related deaths in mice were
> caused by cancer and what percentage were caused by other ailments.
I would guess that Steve Harris could give reasonably accurate numbers.
> Parsimony is often not favoured in biological systems where genetic
> drift and natural selection can result in a wide variety of solutions
> to a single problem.
That's not a usual use of the term "genetic drift", but other than that
I fully agree. What we can say, however, is that rather closely related
species are more likely to do things the same way than disparate species.
The question thus comes down to a gut feeling of "Are all mammals close
enough to each other that differences in their mechanism of aging are
unlikely?" Most of us would say yes, but we wouldn't put money on it.
(I am currently working on getting Barja some bats...)
Aubrey de Grey
fre...@webtv.net
to re do it later tonight when I have more time. Now here is my very
short response, to your latest post.
Aubrey writes:
>This is absolutely wrong. I can assure
>you that the only surprise was the ease
>with which Geron did what they did,
>simply because most experiments take a
>good deal of fine-tuning before they
>work. The central role of telomere
>shortening as the mediator of replicative
>senescence has been accepted for many
>years.
Below is a page, and the first line from a quote by Titia de Lange on
the controversy with telomeres and cell senescence.
Titia de Lange
"All's well that ends well, and so it goes for the decade-old debate on
the role of telomere shortening in the senescence of cells."
http://www.sciencemag.org/feature/data/telomerase/delange.shl
>As to cancer, likewise, no one ever said
>that cancer would be caused by
>telomerase, only (as Shay explains in the
>Discover article you mentioned) that it
>would make human (but not mouse) cells
>less well defended against cancer. This
>is still the general view, and there is no
>new evidence against it -- the only
>relevant study involved growing
>telomerase-positive human cells in a
>mouse and noting that they didn't
>become cancerous in the duration of the
>study, which was only two months. (See
>Nature Genetics 21:111-114.) The
>absence of cancer for two months in a
>population of only a few million cells
>does not prove that the cells are no more
>prone to cancer than
>telomerase-negative cells, and no one in
>the telomere research community claims
>that it does prove that.
Shay has made many comments on the point, of telomerase not leading to
cancer. Here is another instance of him defending the case that
telomerase would not cause cancer.
"Telomerase, though, is running full bore in cancer cells, suggesting
that reintroducing it could corrupt normal cells, spur runaway growth,
and lead to tumors."
Yet that's not the case, says Harley. Cancer cells have other properties
that make them malignant. "The mere act of having telomerase doesn't
cause cancer, it just allows the cells to divide," he says."
http://www.sanfran.com/SF9811Geron.html
I will get back with much more latter. My apology once again for the
lost post. It was a good one--Dwight
Tom Matthews
>
> Tom writes:
>
> >But a very excellent and necessary 'rant'.
>
> >All that I want to add to this is:
> >Even if it were true that telomerase
> >advances are leaping ahead while
> >research into other causes of aging is
> >getting nowhere (quite reasonable
> >considering the different levels of
> >promotion, media attention and funding),
> >since telomere shortening appears to be
> >the proximate cause of *few current
> >deaths*, all that research will not help
> >any of us to live any longer!
> >We need to find and to research those
> >fundamental factors which determine the
> >*current* maximum human lifespan. We
> >also very much need to find ways to
> >demonstrate that these some factors
> >'underlie' the major terminal diseases (or
> >not - it is an open question which I think
> >is true).
>
If any individual carefully studies and changes hir lifestyle to
constantly incorporate all the latest achievable health and antiaging
information (CR, high nutrient food, elimination of harmful useless
food, optimal amount and type of exercise, supplements, hormonal
replacement, certain drugs, etc), then I think that s/he has an
excellent chance of becoming part of a very squared human survival curve
and making it to 110 or more.
For me that is still almost 50 years away and I expect during that time
major breakthroughs will have increased the human lifespan barrier.
Hopefully, some of these will also apply to eldery persons like I will
by then be.
fre...@webtv.net
| Client Version: | &vers; |
| Your Connection Rate: | &rate; |
fre...@webtv.net
turned off. The remove sig button, and the send button are right next to
one another, and I hit send by accident--Dwight
Randall Parker
Your comments here bear repeating.
If anyone reading here wants to live longer your best bet for doing so is
to write letters to the political leaders who make the research funding
decisions to ask them to shift the relative weighting of those funds to
heavily toward basic research into the molecular mechanisms of aging.
In article <7oemkb$q1g$1...@pegasus.csx.cam.ac.uk>, ag...@mole.bio.cam.ac.uk
says...
Thomas Mahoney
says...
(snip)
I apologize for stepping in so late in this thread. I haven't been keeping
up with the NG for a while and missed some of the discussion.
>The hypothesis that telomere shortening may play a bigger role in long-
>lived mammals than in short-lived ones is unattractive in parsimony
>terms, but not so much so as to be rejected out of hand in the absence
>of data. Therefore it would certainly be valuable to devise a measure
>of this in long-lived mammals that can be done more quickly than by
>observing life histories of animals that are not yet born.
The work with Dolly and the cloned cows mentioned are providing some
significant data that is harmonious with the telomeric theory of aging.
Telomeric length of cellular systems is proving to be the most predictive
bio-marker of aging of both the cells and the organism in question. While
there is still no substantive evidence showing that telomeric loss actually
leads to death and the upper limit of life span, it has been well accepted
that telomeres in reproducing cells, absent telomerase, are significantly
shorter in an aged organism than in a younger one.
This shortening is not uniform between tissues nor even in cell lines within
the same tissue. Numerous variables such as contact inhibition, experienced
trauma and disease process etc... will have an influence on the replicative
history of any particular cell line within a system.
>One approach to this seems to me to be very simple indeed: to determine
>telomere length of fibroblasts at death of people who died of aging-
>related causes. Clearly the telomere length of fibroblasts is unlikely
>to have an actual causative influence on age-related pathologies, but it
>is likely to be well correlated to telomere length elsewhere in the body,
>because the telomere length in a given cell at a given age is determined
>by its length in the zygote and the cell's somatic "life history". So,
>people who die of aging-related causes at a relatively early age should
>(if telomeres matter in such causes) tend to have rather short fibroblast
>telomeres for their age. However, as far as I know this has never been
>asked. In fact, rather to my surprise I could not even find a study of
>my presumption above that telomere lengths correlate across tissues (i.e.
>that people with short fibroblast telomeres have short telomeres in
>other tissues too). Perhaps Tom Mahoney knows of one.
>
>Aubrey de Grey
I am a bit surprised at this analysis. It appears to be contrary to the
arguments previously presented showing that fibroblast aren't directly
correlated with aging in vivo, in particular, the Cristofalo studies, (J Cell
Physiol 1999 Apr;179(1):11-7).
The heterogeneity of telomere length in various tissues in the elderly was
demonstrated by Butler MG, et al, in, (Cancer Genet Cytogenet 1998
Sep;105(2):138-144).
Even determining the telomeric length of the tissues that caused the death of
the subject may not provide a clear picture of the effects of telomeric
shortening. The vast majority of cells, that have critically shortened
telomeres, initiate apoptosis and the remaining cell lines may not reflect
the shortening that has previously occurred in unrelated cell lines.
A loss of cellular mass, ie; a thinning of vascular walls, etc... may be the
only indication that some cell lines have reached the end of their
replicative potential due to telomeric loss.
To complicate things a little further, it appears that mechanisms other that
aging can cause abrupt telomere shortening leading to sudden senescence
syndrome, (Rubelj I, Vondracek Z, J Theor Biol 1999 Apr 21;197(4):425-38).
My evaluation of this data is that telomeric shortening can be specific in
particular tissues or even cell lines within a tissue. This can lead to a
degradation of that system and may cause the death of the organism. These
differential replicative histories of cell lines may result in the "aging"
diseases such as arteriosclerosis and stroke etc...
Testing other tissues in the body would not reflect this phenomena and would
likely correlate with the age of the organism and/or still retain significant
telomeric length as in the case of fibroblasts.
Thomas Mahoney, Pres.
Lifeline Laboratories, Inc.
http://home.earthlink.net/~excelife/index.html
Aubrey de Grey
Dwight wrote:
> http://www.sciencemag.org/feature/data/telomerase/delange.shl
Sure -- this was the Perspectives accompanying the original Science
article reporting the abolition of replicative senescence. Indeed,
the headline and first sentence make catchy reading. But if you
read the whole article you will see what I mean: the only negative
evidence anyone ever put forward regarding the role of telomere
length in replicative senescence was from mice. And indeed, it is
still widely believed that telomerase-positive mouse cells will NOT
be immortal (though I believe this has not yet been tested, probably
because nobody really cares). de Lange's ref. 6, from 1992, was the
absolute clincher in most people's view, but even before that there
was pretty general agreement that telomere length was the main thing
-- in HUMAN cells.
> Shay has made many comments on the point, of telomerase not leading
> to cancer. Here is another instance of him defending the case that
> telomerase would not cause cancer.
Yes, but he's not addressing the research community. Shay, Harley and
others are not defending that case against other specialists who think
(or thought) that telomerase would cause cancer, because there aren't
any such specialists and there never have been. He's defending it
against laymen who have heard one fact (that cancers have telomerase)
and don't have the background to judge it. (That's no criticism of
laymen, of course.)
> Furumoto et al, "Age-Dependent Telomere Shortening is Slowed Down by
> Enrichment of Intracellular Vitamin C Via Suppression of Oxidative
> Stress," Life Sciences 63(11):935-948 (1998)
Looks interesting, and certainly consistent with work by von Zglinicki
(e.g. Exp Cell Res 1995 Sep; 220(1):186-193). But the problem with
extrapolating these results to what goes on in the body is that it
only applies to cells which are (a) grown in air, as opposed to the
much lower oxygen concentrations in the body, and (b) grown at all,
i.e. dividing. Cells that are kept in a non-dividing state don't
show any telomere shortening (see Free Radic Biol Med 24(6):885-893).
von Zglinicki's model is that there is oxidative damage to telomeric
DNA (just as to all DNA) but that it is single-strand damage, which is
repaired perfectly well (though maybe not quite as fast as non-telomeric
DNA) so long as the chromosome is not replicated in the meantime. So
what this adds up to is that cells whose telomeres don't shorten from
cell division (because they aren't dividing) also don't have them
shorten from oxidative damage. Cells whose telomeres DO shorten from
cell division (because they divide a lot) may also have them shorten a
bit faster from oxidative damage, but there is no reason (as far as I
know) to suppose that the damage has nearly as much of an effect as
the division.
> Shay and Wright have stated, in the past, some very bold predictions,
> of what they thought the effect would be, of turning telomerase on,
> in the different cells of the body. They lose credibility, in the
> scientific community, for stating what they see, but have not yet
> proved.
They would have lost credibility if they had stated more than they
could justify, but they didn't and don't (in the scientific community).
As I said earlier they are somewhat guilty of allowing others to get
away with overinterpreting what they say, but that's not the same thing
at all. (Though it has lost them a bit of credibility with some of us.)
> I think, that they are men who think, that they are on the
> right track, to solving the mystery of aging. What a passion this must
> give them, and how hard it must be, to try and stay within the bounds,
> of what they can prove.--Dwight
You're right there. The same goes, of course, for those of us following
other anti-aging research avenues. But we (like they) do stay within
those bounds, because otherwise we wouldn't be helping each other to
push the science forward.
Aubrey de Grey
Aubrey de Grey
Tom Mahoney wrote:
> >Clearly the telomere length of fibroblasts is unlikely
> >to have an actual causative influence on age-related pathologies, but it
> >is likely to be well correlated to telomere length elsewhere in the body,
> >because the telomere length in a given cell at a given age is determined
> >by its length in the zygote and the cell's somatic "life history".
...
> I am a bit surprised at this analysis. It appears to be contrary to
> the arguments previously presented showing that fibroblast aren't
> directly correlated with aging in vivo, in particular, the Cristofalo
> studies, (J Cell Physiol 1999 Apr;179(1):11-7).
I may have been unclear. Certainly, fibroblast telomere length doesn't
change with age -- simply because fibroblasts hardly ever divide in vivo.
But the telomere length they have (throughout adult life) may nonetheless
correlate with telomere length of the individual as a zygote. One could
test this by taking multiple samples from multiple individuals and asking
whether the variability between samples from the same individual is less
than the variability between samples from different individuals.
> Even determining the telomeric length of the tissues that caused the death
> of the subject may not provide a clear picture of the effects of telomeric
> shortening. The vast majority of cells, that have critically shortened
> telomeres, initiate apoptosis and the remaining cell lines may not reflect
> the shortening that has previously occurred in unrelated cell lines.
>
> Testing other tissues in the body would not reflect this phenomena and
> would likely correlate with the age of the organism and/or still retain
> significant telomeric length as in the case of fibroblasts.
This is all absolutely true, but it doesn't alter my point. If someone
starts off as a zygote with rather short telomeres, and if that short
telomere length translates into rather short telomeres of all tissues
in the adult, and if shortness of telomeres is causative of age-related
pathologies, then this short-telomered person will be living closer to
the edge than a long-telomered person. The specific cause of death (e.g.
the tissue that failed) may not be explicitly indicative; all I'm saying
is that the _probability_ of the short-telomered person suffering from
critically short telomeres in some tissue is higher than for a long-
telomered person because the amount of shortening that would have to
occur is less.
Aubrey de Grey
fre...@webtv.net
>Yes, but he's not addressing the
>research community. Shay, Harley and
>others are not defending that case
>against other specialists who think (or
>thought) that telomerase would cause
>cancer, because there aren't any such
>specialists and there never have been.
>He's defending it against laymen who
>have heard one fact (that cancers have
>telomerase) and don't have the
>background to judge it. (That's no
>criticism of laymen, of course.)
If you look below, it looks as though there are researchers trying to
promote the idea, that telomerase will cause cancer, or at least give
that impression to the general public. I think some of this may be a
hold over, from the days when Hayflick was ridiculed by the experts of
his day, for proposing that human cells were not immortal. Of course
some of this talk, about telomerase and cancer, is caused by a lack of
understanding on the correlation between the two subjects.
http://more.abcnews.go.com/sections/living/DailyNews/telomerase981228.html
"Telomerase does not cause cancer progression," said Woodring Wright of
the UT Southwestern Medical Center in Dallas, a co-author of the study,
published Tuesday in the January issue of the journal Nature Genetics.
"The abnormalities seen in cancer are due to other mutations."
Other researchers said the experiment is too limited to exonerate
telomerase. They said that while telomerase may not cause
cancer by itself, it appears to play a fundamental role in the growth of
cancerous cells, even if the cancer itself is triggered by, say,
radiation or a virus.
>They would have lost credibility if they
>had stated more than they could justify,
>but they didn't and don't (in the scientific
>community). As I said earlier they are
>somewhat guilty of allowing others to get
>away with overinterpreting what they
>say, but that's not the same thing at all.
>(Though it has lost them a bit of
>credibility with some of us.)
Yes I remember the small backlash when they stated, that they had
discovered or found the "fountain of youth." I think they really believe
what they originally said, but knew it had to be scientificlly proven,
to be accepted universally.
>You're right there. The same goes, of
>course, for those of us following other
>anti-aging research avenues. But we
>(like they) do stay within those bounds,
>because otherwise we wouldn't be
>helping each other to push the science
>forward.
>Aubrey de Grey
I think we have to a little more tolerant, of free speech in the
scientific community, especially on the positive side. The scientific
community has not always been right, and the scientific method has not
always been accurate, or truth revealing.
Do you have any thoughts on Tankerase?(I think that is the right
spelling<G> )--Dwight
Aubrey de Grey
Dwight wrote:
> If you look below, it looks as though there are researchers trying to
> promote the idea, that telomerase will cause cancer, or at least give
> that impression to the general public.
...
> http://more.abcnews.go.com/sections/living/DailyNews/telomerase981228.html
Right, you have put your finger on it. Any scientist who does anything
newsworthy is required to summarise it in a totally inadequate number
of words for general consumption, and so are their colleagues. So,
here you have a classic case of the people who did the work doing as
they must in the interests of their funding, i.e. allowing a bit of
overinterpretability to creep into what they say, and on the other hand
you have their colleagues restoring some balance by sounding (but not
actually saying anything specific) a bit more negative than reality. I
assure you again: Wright and de Pinho do not have and never have had an
iota of disagreement over this subject. Not one statement by any of
the specialists quoted in the various pages you have cited would be
remotely disputed by any of the other specialists quoted. The only
difference is in the spin.
It's a grim business, talking science to the media. Very few of us are
any good at it. If science didn't cost money, you would never hear a
hoot out of any of us, except in fora like Usenet where we can say as
much as we like and respond to any misinterpretations that may result.
> Yes I remember the small backlash when they stated, that they had
> discovered or found the "fountain of youth."
I defy you to show me where they ever said that.
> Do you have any thoughts on Tankerase?(I think that is the right
> spelling<G>)
I've never heard of it.
Aubrey de Grey
Lars Gollub
>>You're right there. The same goes, of
>>course, for those of us following other
>>anti-aging research avenues. But we
>>(like they) do stay within those bounds,
>>because otherwise we wouldn't be
>>helping each other to push the science
>>forward.
>>Aubrey de Grey
>
>I think we have to a little more tolerant, of free speech in the
>scientific community, especially on the positive side. The scientific
>community has not always been right, and the scientific method has not
>always been accurate, or truth revealing.
My impression of a competition (negative sense) between the
different "avenues" can't be all wrong. Why don't just team up?
Of course the stakes are high for the companies but some
exchange should speed things up. I can't belive (any more)
that there is *the* key to find (maybe there is a *last* key).
The puzzle seems to consist of a lot of parts and only if it is
completed, the companies can make money out of their part.
Just some thoughts...
>Do you have any thoughts on Tankerase?(I think that is the right
>spelling<G> )--Dwight
Tankerase? Do you know a source about it? (It isn't a joke, isnt it?
An enzym erasing tanks?) :o)
Best regards,
Lars
fre...@webtv.net
>>Tankerase?(I think that is the right
>>spelling<G> )--Dwight
>Tankerase? Do you know a source about
>it? (It isn't a joke, isnt it? An enzym
>erasing tanks?) :o)
>Best regards,
>Lars
My jokes are usually a little better, than my spelling.<G> If you wish
to have an enzyme for erasing tanks, than I will run some experiments,
with my Atari Combat cartridge.<G>--Dwight
Tankyrase, a poly(ADP-ribose) polymerase at human telomeres.
http://www.ncbi.nlm.nih.gov/htbin-post/Entrez/query?db=m&form=6&uid=9822378&dopt=r
fre...@webtv.net
>>Yes I remember the small backlash when
>>they stated, that they had discovered or
>>found the "fountain of youth."
Aubrey writes:
>I defy you to show me where they ever
>said that.
I will see if I can find the exact press release, but it did get said.
It was quoted many times afterwards.
http://more.abcnews.go.com/sections/tech/DailyNews/dye39.html
The Fountain of Misnomer
In a formal press release, the university said the researchers had
discovered a "cellular fountain of youth." Technically, that may be true
in that it appears the scientists were able to keep the cells alive and
productive, but that expression is loaded with meaning that goes far
beyond the research.
The announcement caused a media firestorm, and in various interviews the
scientists offered more cautious statements, but the damage had already
been done. My guess is that most people now think we are a significant
step closer to immortality.
Dwight writes:
>>Do you have any thoughts on
>>Tankerase?(I think that is the right
>>spelling<G>)
Aubrey writes:
>I've never heard of it.
>Aubrey de Grey
Sorry about the spelling error--Dwight
Aubrey de Grey
Dwight wrote:
> Tankyrase, a poly(ADP-ribose) polymerase at human telomeres.
Ah yes, sorry -- I thought it rang a bell but I didn't have time to
explore. Yes, this is one of the telomere-associated factors that
de Lange has identified over the past few years. The basic reason
why telomere maintenance is complicated (involving lots of proteins)
is that it is vital to stop the DNA repair systems of the cell from
identifying a telomere as a broken chromosome and stitching it onto
the end of another chromosome. I have no other thoughts.
> I will see if I can find the exact press release, but it did get said.
...
> In a formal press release, the university said the researchers had
> discovered a "cellular fountain of youth."
Sure, the university said, in a press release. The researchers didn't.
> The announcement caused a media firestorm, and in various interviews the
> scientists offered more cautious statements, but the damage had already
> been done. My guess is that most people now think we are a significant
> step closer to immortality.
Indeed, as demonstrated very often on this group and elsewhere. The
only question is whether it's right to call it "damage". Many people
would put this sort of media manipulation in the same category as the
sort of pseudoscience-based supplement-pushing we're so familiar with,
but I don't think that's fair. Even though I don't work on telomeres
and don't think that telomere maintenance will single-handedly extend
human lifespan, I consider it a good thing that most people now think
we are a significant step closer to "engineered negligible senescence"
(a safer phrase, I think!), because they're right, we are -- just not
for the reason they think. Biogerontology is moving forward on all
fronts, and the scientists whose funding benefits from this sort of
media manipulation are not restricted to those in the narrow field that
is in the news. There is still nowhere near enough money in anti-aging
research, but there's a lot more than there used to be, and I venture
that there is more than there would be if the telomere crowd had made
sure their work was only represented accurately. When someone (either
a government agency or an individual) gets interested enough in funding
anti-aging research to talk to the people who are doing it, it doesn't
usually take very long at all to educate them; the hard part is getting
them that interested in the first place, and I don't honestly care how
that is done.
Aubrey de Grey
Andrew Mason
> > Parsimony is often not favoured in biological systems where genetic
> > drift and natural selection can result in a wide variety of
solutions
> > to a single problem.
> That's not a usual use of the term "genetic drift", but other than
that
> I fully agree.
Aubrey
You are quite correct, my use of the term "genetic drift" was
imprecise. I did not intend it in the sense of neutral drift at the
molecular level. My intended meaning was more along the lines of
increased genetic divergence due to random mutation during periods of
weak selection.
fre...@webtv.net
>Sure, the university said, in a press
>release. The researchers didn't.
It was a quote attributed to them, in the press release. Here is the
quote and the link---which UT Southwestern scientists call a "cellular
fountain of youth" -- causes human cells grown in the laboratory to
retain their "youth" http://www.swmed.edu/news/lifespan.htm >Indeed,
as demonstrated very often on >this group and elsewhere. The only
>question is whether it's right to call it >"damage". Many people would
put this
>sort of media manipulation in the same
>category as the sort of
>pseudoscience-based
>supplement-pushing we're so familiar
>with, but I don't think that's fair.
I didn't think it was fair, but I don't think many of the attacks on the
supplement companies have not been fair either. Pearson and Shaw come to
mind, even though they were promoting the concept, of supplements for
aging, with no supplements they sold, at the time.
>Even
>though I don't work on telomeres and
>don't think that telomere maintenance
>will single-handedly extend human
>lifespan, I consider it a good thing that
>most people now think we are a
>significant step closer to "engineered
>negligible senescence" (a safer phrase, I
>think!), because they're right, we are --
>just not for the reason they think.
It may not extend lifespan, but it looks like it may effect all other
areas associated with aging. Would free radicals be a problem, or AGE
damage in cells, in cells that were young and immortal?
>Biogerontology is moving forward on all
>fronts, and the scientists whose funding
>benefits from this sort of media
>manipulation are not restricted to those
>in the narrow field that is in the news.
>There is still nowhere near enough
>money in anti-aging research, but there's
>a lot more than there used to be, and I
>venture that there is more than there
>would be if the telomere crowd had
>made sure their work was only
>represented accurately. When someone
>(either a government agency or an
>individual) gets interested enough in
>funding anti-aging research to talk to the
>people who are doing it, it doesn't
>usually take very long at all to educate
>them; the hard part is getting them that
>interested in the first place, and I don't
>honestly care how that is done. Aubrey
>de Grey
I agree, that the enhancement of money, and maybe more importantly the
increase in public awarness, is very important. If anti-aging is to have
a team, then that team needs to support more, and criticize less, at
least in the public domain It was not that long ago, that anti-aging was
considered quackery, as was immortality. It is kind of nice, to see the
people who have questioned my sanity, for the last twenty years, now
have to question their's.<G>
I think a major step, in speeding the science up, is the more direct use
of human volunteers, for this research. Why do we not have human cells
extracted, and immortalized, and not reimplanted into their hosts? We
can always fill in the blanks later. Can you imagine the headlines<G>,
and no I don't think it would harm the volunteers. Or another way of
thinking of it, we lose more people every day from aging, then we could
ever lose, from the research to prevent it. Maybe I am crazy, but maybe
I am not<G>--Dwight
Aubrey de Grey
Dwight wrote:
> It was a quote attributed to them, in the press release.
Yes, but I still maintain that it was misquoted (or, at very least,
quoted out of context).
> I didn't think it was fair, but I don't think many of the attacks on
> the supplement companies have not been fair either. Pearson and Shaw
> come to mind
Yes - very hard-working and well-informed people.
> It may not extend lifespan, but it looks like it may effect all other
> areas associated with aging.
I think I must misunderstand you. How can something affect all other
areas associated with aging but not extend lifespan?
> Would free radicals be a problem, or AGE
> damage in cells, in cells that were young and immortal?
Sure! They are mainly a problem at the moment in cells that do not
divide at all, because division is great -- it dilutes away damage,
because before a cell divides it has to grow, and that involves the
synthesis of lots of new protein and lipid which starts off pristine.
> If anti-aging is to have
> a team, then that team needs to support more, and criticize less, at
> least in the public domain
Yes as between different avenues of research, and that is why I cut
people who work on telomeres such a huge amount of slack with regard
to this overinterpretability we've been discussing. Ostensibly it is
a good deal more reprehensible than I describe it, but I think it's
justifiable for the reasons I outlined yesterday. However, it is
still crucial to focus people (and money) on the research avenues
that are being pursued by rigorous scientific methods, and away from
those that are throwing the money down the drain.
> I think a major step, in speeding the science up, is the more direct
> use of human volunteers, for this research. Why do we not have human
> cells extracted, and immortalized, and not reimplanted into their hosts?
Why not, indeed? But remember that this was only done in mice less than
a year ago (Nature Genetics 21:111-114). This is most of why Geron have
teamed up with the embryonic stem cell people and the cloning people.
Aubrey de Grey
fre...@webtv.net
>>like it may effect all other areas
>>associated with aging.
Aubrey writes:
>I think I must misunderstand you. How
>can something affect all other areas
>associated with aging but not extend
>lifespan?
Your going to hate me for this one<G>, but there maybe an X factor, that
we are yet unaware of, and if there is, then it might be in the brain. A
possible theory was put for years ago, for a death hormone. It is just a
wild hunch. I have felt for sometime, that aging and maximum lifespan
may be different subjects. Again, it is not scientific, but just a
hunch, and I hope the hunch is wrong.
The skewing, of where the money goes, seems to have more to do with
popular concepts, and whether the answers can be patented. Twenty years
ago I cared allot about this point, but now it looks as though we may
get to our goals anyways.
>>I think a major step, in speeding the
>>science up, is the more direct use of
>>human volunteers, for this research.
>>Why do we not have human cells
>>extracted, and immortalized, and not
>>reimplanted into their hosts?
>Why not, indeed? But remember that this
>was only done in mice less than a year
>ago (Nature Genetics 21:111-114). This
>is most of why Geron have teamed up
>with the embryonic stem cell people and
>the cloning people.
>Aubrey de Grey
I know it will come in the future, but I think more answers would come
faster without the use of the mice. Take some of the immune cells, from
people dying of aids or cancer, and, if we can, immortalize them. Put
them back in, and see what the effects will be. I doubt that more people
could die from speeding up the process, then it would save in the long
term.
Stem cells have an excellent near future, in my opinion, and not
necessarily just embryonic stem cells. The cloning knowledge maybe
helpful, in the more distant future. We live in interesting
times--Dwight
Have a good day Aubrey
Jane Axtell
<andre...@my-deja.com> wrote:
> (snip) my use of the term "genetic drift" was
> imprecise. I did not intend it in the sense of neutral drift at the
> molecular level. My intended meaning was more along the lines of
> increased genetic divergence due to random mutation during periods of
> weak selection.
>
> Andrew
>
Life extension and other attempts at designed outcomes across large
societal groups can have some amazing selective results.
This came home to me when my daughter was "blooming" into the typical
partner selection age. Where were the vividly vital young men who had
brightened the landscape of my own youth? The world seemed occupied by
gray timid substitutes.
Then one day i saw the missing type... a busload of them. My daughter was
with me and she caught their collective attention.
Unfortunately this was the jail bus. The future opportunities of the
riders were becoming somewhat more limited than this type once enjoyed.
Opportunities now come to quieter men, men who tolerate long hours sitting
without collapsing in constipated paroxysms of grief for room to move
about. Men who can spend large sections of their lives doing what is
personally meaningless and without visible product. Men who do as they are
told and think what they are paid to think. (No amount of tongue piercing
or hair bluing can conceal the inneer vacuum.)
We are considering an online magazine covering the future as a
full-participation design projet. Would you care to consider keeping us
aware of the "weak selection" and bizarre selection effects of what is
proposed?
Your future friend,
Jane Axtell
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Designs for Life in a Galactic AEON