[ExI] reverse aging
avantguardian2020 at yahoo.com
Mon Dec 6 04:49:13 UTC 2010
----- Original Message ----
> From: Ben Zaiboc <bbenzai at yahoo.com>
> To: extropy-chat at lists.extropy.org
> Sent: Wed, December 1, 2010 5:17:38 AM
> Subject: Re: [ExI] reverse aging
> Interestingly, Aubrey de Grey's SENS includes a scheme for totally eliminating
>all cancers, by taking the opposite approach: Get rid of telomerase and all
>other means of lengthening telomeres. Of course, that brings its own problems,
>but it stops cancer dead in its tracks.
When I first read this, I thought it was very naive. So I looked up a detailed
description of his strategy here:
My objections to it follow:
1. First what he was suggesting was similar to purposefully giving people the
equivalent of dyskeratosis congenita, a genetic birth defect where people are
born without normal telomerase function. The problem is that these people are
actually *more* prone to cancer and start getting them around ten years old. You
can find a complete medical description of dyskeratosis here on pubmed for free:
2. The second reason is that once a cell violates its genetic programming and
goes cancerous, all the rules go out the window. If telomerase is available, it
will use it to lengthen its telomeres. If telomerase is not available it will
start using alternative
methods to lengthen its telomeres like using the homologous recombination
normally reserved for DNA repair and meiosis of germline cells.
And if that doesn't work, cancer cells have no qualms against just sticking
chromosomes together end to end with non-homologous end joining. Cancer cells
will duplicate genes or entire chromosomes (polyploidy), lose genes or entire
chromosomes, and mix bits and pieces of different chromosomes together if need
So profound is a cancer cell's ability to mutate at fast speed that it can form
structures known as ring chromosomes that recapitulate the ancestral bacterium's
circular telomere-independent chromosome.
In short, cancer cells have all the tools of evolution at their disposal at
speeds normally associated single-celled organisms.
3. The next problem is that de Grey's strategy underestimates the importance
of the immune system in cancer prevention. This process is called
immunosurveillance and mice and people with defective immune systems are
notoriously prone to cancer. The white blood cells that normally protect people
from cancer *need* telomerase to function properly because the mechanism by
which they operate depends on the mass replication of the white blood cell
lineages that can recognize and kill tumor cells.
Of course this mechanism of amplification of the efficacious clones is used to
combat mundane infections as well. So not only would telomerase-deficiency make
one prone to cancer, it would make one susceptible to death from normally benign
viral, bacterial, and fungal infections.
4. De Grey's solution to this problem is "reseeding" whereby engineered stem
cells are periodically given to people to replace high turnover tissues such as
the blood cells, skin, and gut epithelium. This work-around however brings
up the next problem: The relationship between cancer and stem cells is
poorly understood and these reseeded stem cells could very well *become*
And if the stem cells are treated to lack telomerase, like the rest of the cells
of the body in WILT, they no longer qualify as stem cells since the capacity for
self-renewal is one of the defining characteristics for stem cells. So these
telomerase deficient stem cells would be the medical equivalent of GM food crops
that can't make seeds, requiring one to be beholden to whatever biotech company
happens to be manufacturing your crippled stem cells for you. If we are talking
immune system stem cells, then catching a simple cold could deplete ones entire
resevoir of non-self-renewing hematopietic stem cells.
5. Aside from the theoretical problems with the WILT strategy, the technical
challenges would be horrendous. With the current state of the art, gene
knockouts are a messy and rather hit or miss affair. They involve trying the
targeted gene deletion on a great many embryos, then screening for that one
precious embryo or cell line in which it worked. While this is feasible with
mice, the bioethicists would have a canniption if you tried that with human
embryos. But what use is a gene knockout of an embryo going to be to an already
full grown population of possible cancer victims? While gene knockouts are done
routinely on human cells in a petri dish, I am not aware of any existing
technique that would allow one to delete a gene from all 10^14 cells of an adult
human in vivo:
So my final analysis is that de Grey's strategy is inelegant, convoluted, and
unlikely to work in a time and cost frame that would make it competitive with
other developing cancer treatments. Top-down management seldom works in
bottom-up organized systems. Such seems to be as true in biology as it is in
From: Adrian Tymes <atymes at gmail.com>
>To: ExI chat list <extropy-chat at lists.extropy.org>
>Sent: Wed, December 1, 2010 9:26:33 AM
>Subject: Re: [ExI] reverse aging
>What if you extended the telomeres, such that the only way senescence would
>set in is via damage leading to cancer?
In theory, this could work but there are several very serious technical
Maybe add in a very slow telomere
>extending enzyme, that replaces telomeres fast enough for normal cell division
>replace worn out cells) but can't keep up - or even goes into reverse - if very
>cell division is encountered (such as in cancer). Might that work?
The main technical challenges would be coming up with a molecular design
for your custom enzyme and then getting it into all the cells of the adult
human, without disrupting any important housekeeping genes.
Since using protein folding at home, super computers, and other brute force
methods give limited results on predicting the structure of existing proteins
from their sequence data, it would be even more of a pain to design a
novel enzyme to fold and function the way you would like. Especially because you
would need to figure out how to regulate its function based on the pace of cell
you envision it.
Then, even if you had this fantastic new enzyme, how would you deliver it to all
the 10^14 cells in an adult? Most gene therapy vectors can only target a
single cell type. Now you could transfect your custom enzyme gene into human
embryos and create a race of transgenic humans but that doesn't do your average
babyboomer any good.
Now I am not trying to discourage anyone here, but bioengineering humans to live
longer is not going to a quick fix. Part of the problem is that human cells
evolved to replicate like crazy in the first 20 or so years of life allowing for
a single-celled embryo to become an adult human and then suddenly cut back to
the considerably slower levels of cell replication required for homeostatic
maintenance for the remaining 60 years.
Despite this fact, when high-turnover tissues are considered, approximately 75%
of these cell divisions happen after maturity. So any intervention to completely
halt cell division in order to prevent cancer will likely end up being worse
than the disease.
"There is nothing wrong with America that faith, love of freedom, intelligence,
and energy of her citizens cannot cure."- Dwight D. Eisenhower
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