

Telomerase Therapies in Our Future - mrfusion
http://joshmitteldorf.scienceblog.com/telomerase-as-a-fountain-of-youth/

======
oskarpearson
After a quick search, much of the TA-65 commentary seems to be well-placed
SEO-optimised junk. Some of it seems like it could be 'affiliate program'
stuff too. If you can add to the debate sensibly, consider contributing here
or upvoting: [http://skeptics.stackexchange.com/questions/8967/does-a-
mole...](http://skeptics.stackexchange.com/questions/8967/does-a-molecule-
called-ta-65-reverse-aging-in-humans)

While trying (perhaps unsuccessfully) to avoid an ad-hominum attack, here's
some other info on the author:

Positive, perhaps:
[https://lifeboat.com/ex/bios.joshua.mitteldorf](https://lifeboat.com/ex/bios.joshua.mitteldorf)

Negative, perhaps:
[http://www.scientistsfor911truth.org/mempages/Mitteldorf.htm...](http://www.scientistsfor911truth.org/mempages/Mitteldorf.html)

~~~
reasonattlm
TA-65 is indeed a bunch of herbal junk, sold by the usual suspects.

Mitteldorf on the other hand is a legitimate theorist with a programmed aging
viewpoint, e.g. that the best approach to aging is to find differences in
levels of gene products and push those levels back to being closer to what
they were in youth - to revert the program. You can probably see why he's
interested in anything that might provide a step towards studies that could
add supporting evidence, even if not effective to a practical level.

[http://www.ncbi.nlm.nih.gov/pubmed/?term=Mitteldorf%20J%5BAu...](http://www.ncbi.nlm.nih.gov/pubmed/?term=Mitteldorf%20J%5BAuthor%5D)

Not a view I agree with, as I see the balance of evidence supporting the more
mainstream view of aging as a consequence of accumulated damage, with these
changes in gene product levels being a response to that damage. Aging research
is certainly a field with a lot of varied opinions on what exactly is going on
under the hood. Still, programmed aging is a minority camp at this time,
albeit a very vocal one.

~~~
oskarpearson
Thanks for taking the time to reply. I'll look into him more.

Also: the first time you hit the above link above, the site gives a 'no
history' error and doesn't return any results - which is unintentionally
funny, I guess. :) Searching does return some results though!

------
paulsutter
> In fact, evolution has not worked to maximize life span, but only to make it
> sufficient to assure time for reproduction.

Longer life spans would /slow down/ evolution. Evolutionary lines with very
long lifetimes would evolve more slowly than evolutionary lines with shorter
lifetimes, and would be quickly overtaken by them.

Of course, all of us alive today would be happy to make that trade off going
forward ;)

~~~
M8
Does evolution matter for a species where every sick offspring is saved at
birth?

~~~
btilly
Yes. Because we still have a situation where not every person becomes a
parent, and those that do have wildly different numbers of offspring.

------
reasonattlm
To date progress in the development of stem cell treatments has been
accompanied by a markedly lower risk of cancer than was expected at the
outset. The characteristic decline in stem cell activity with age is believed
to be an evolutionary adaptation that reduces cancer risk: there is a balance
between on the one hand the risk of cancer due to over-active damaged cells,
and on the other hand the failure of tissues and organs due to loss of
maintenance activities on the part of stem cells. It is the responsibility of
stem cells to deliver supplies of fresh, fit cells as needed to replace those
that have become damaged, worn, or have reached the inherent limits imposed on
replication of somatic cells. That supply tapers off in old age, however, as
stem cells gather damage and spend ever more time quiescent rather than
active.

Despite the comparative lack of cancer resulting from stem cell therapies,
there is still every reason to expect that caution should attend the
development of any therapy that spurs greater regeneration in old tissues. The
cells in those tissues have a higher load of nuclear DNA damage, and thus a
greater cancer risk attends their activity. Yet in practice it isn't working
out to be as great a risk as expected, or at least not so far based on the
data gathered to date. Why this is the case is an interesting question with no
solid answer at this time.

The replication limits of somatic cells depend in part on telomere shortening.
Telomeres are repeated lengths of DNA at the ends of chromosomes. A little of
that length is lost with each cell division, and very short telomeres trigger
cellular senescence or programmed cell death. In comparison stem cells retain
long telomeres, and thus the ability to continually create new daughter
somatic cells with long telomeres to deliver into the tissues they support.
This maintenance of telomere length in stem cells is achieved through the
activity of telomerase, an enzyme that adds repeated DNA sequences to the ends
of chromosomes.

Based on all of the above, it is not unreasonable to expect that more
telomerase activity in more cells would mean a greater risk of cancer. It
would mean cells being more active, and older, more damaged cells being more
active. In mice, however, this is not what happens. The risk of cancer
actually falls, even as life span is lengthened: researchers believe there is
increased stem cell activity and tissue maintenance, but not enough time in
even the extended mouse life span for the other shoe to drop and cancer risk
to catch up. A firm and comprehensive analysis of what exactly is going on
inside these mice is probably still a few years away, however. Nonetheless,
the picture painted above suggests that we should be cautious about
extrapolating a beneficial balance of time and cellular activity in mice to
indicate that telomerase treatments would be similarly great for humans. The
span of time is different, our telomere biology is different, and the balance
of aging and cell activity is different.

On the other hand, the medical community seems to be doing pretty well with
stem cell treatments that are just another way of spurring increased cell
activity and tissue maintenance in old, damaged tissues. Enhanced telomerase
activity seems worthy of further investigation for all the same reasons that
stem cell therapies were worthy of clinical development. I don't see
telomerase therapies as a treatment for aging per se, however. The approach of
increased telomerase activity doesn't address the underlying issues that cause
stem cell decline, but instead forces damaged cells to get back to work by
overriding the normal reactions of an aged biochemistry. In the view of aging
as accumulated cellular damage, stem cell failure with age is an evolved
reaction to an increasingly damaged tissue environment. The best way forward
is to repair that environment, not override the signals. As first generation
stem cell treatments have shown, however, it is possible to achieve beneficial
results by taking this path, even while failing to address the root causes of
aging. Benefits are good, but we shouldn't let them distract us from the end
goal.

~~~
narrator
>The characteristic decline in stem cell activity with age is believed to be
an evolutionary adaptation that reduces cancer risk

This isn't science. This is not a falsifiable statement and is not backed up
by any hard evidence. The Reason, with an intentional capital "R" for it could
be just about anything. Biology and evolution are really complicated.

There is a huge negative bias in the scientific community with regards to any
science that can make significant improvements in human lifespan due to
overriding concerns about overpopulation. Thus, the bias when speculating on
any life extension technology is that it will have some sort of negative
consequence.

~~~
reasonattlm
Overpopulation is really not the origin of much negative bias, and where
researchers publish on that topic it is to note that it isn't an issue. E.g.:

[http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192186/](http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3192186/)

However: researchers don't want to be seen as being just another part of the
"anti-aging" marketplace of pills and potions and lies, as it has a negative
affect on their credibility and ability to raise funds for research. That is
the dominant issue, and it has taken a lot of work over the past few decades
to get even more adventurous and strong-willed researchers to the point of
being willing to talk in public about extending healthy human life spans.

------
lvs
It would be charitable to call this article junk science. In particular, the
idea that hTERT expression is a significant cancer risk is quite well-
accepted, but heavily downplayed here. In culture, it's possible to
immortalize a primary cell line (such that it grows indefinitely) by
overexpressing telomerase. In fact, this is how many recent cell lines have
made in multiple fields. The stuff about herbal drugs isn't worth even
discussing.

------
hughes
I find it hard to take seriously an article praising "telomerase-activating
herbs and supplements". Sounds like a marketing piece for alternative
medicine.

