Telomerase Activation

[CoryG]

Does anyone know if there is a relatively simple way to activate
telomerase expression in an animal cell? (not counting animals
naturally expressing it like Lobsters of course)

[Cathal Garvey]

Interrupt base pairing at the promoter with a peptide nucleic acid,
allowing RNA Pol II access.

You can eat them; there's very little that'll degrade them due to the
bizarre fusion of nucleotide and amine backbone. And because they have
little charge, they should penetrate the cell/nuclear membrane pretty
easily.

[CoryG]

I was actually just checking back to add a post asking if they could
make it past the membrane, thanks for the quick response :)

[CoryG]

On another note, since you mentioned eating them being safe, do you
know if there is any specific regulations regarding that/would a
product of it be treated as GM food? The experiment I'm thinking of
is trying to activate it in Tuna muscle tissue and growing them in
bulk without running into the Hayflick limit.

On Oct 19, 5:24 am, Cathal Garvey <cathalgar...@gmail.com> wrote:

[Cathal Garvey]

Bear in mind there are few studies on longevity of PNA in living
tissues; they could be really stable and last a lot longer than you
want. For "lolol immortality" apps, perhaps that's what you want, but be
sure you're testing it super-thoroughly on animal models first.

Come to think of it, if you want to jump a few experimental levels for a
crude crude study, a vial of PNA and some nematodes would be a really
cheap experiment to try in the longevity arena.

[Cathal Garvey]

Caveat: screwing with your DNA with untested orally available DIY
therapies is prone to causing cancer or immediate death. Use with
caution and/or stupidly careless abandon, and don't blame me.

On 19/10/11 10:11, CoryG wrote:

[CoryG]

Yeah, I'd like to complete my phased array before experimenting on
myself in any way that is more or less gauranteed to cause cancer
cells to spring up. I'm pretty certain with a properly tuned phased
array you could target and kill cancer readily, without the metallic
nano particle injections used in dumb-rf solutions to the issue - but
that's still a work in progress.

[CoryG]

Also, if it wouldn't actually be safe to a eat a lot of telomerase-
containing tissue, is there a simple way to remove it without damaging
or contaminating cells, making them inedible?

[Cathal Garvey]

I didn't say it was safe, I said they'd probably survive digestion! :)

I doubt they'd count as a GM food under even a loose interpretation, but
they'd definitely count as unregulated/licensed drugs if you took them
outside the lab?

Also, eating telomerase should be totally safe; as a protein/RNA hybrid,
it just gets digested, right? Any evidence that it survives gut transit?
If not, eating *anything* would probably be toxic, because species
differ in their telomere consensus, and if something capped your
telomeres with the wrong sequence, your native telomerase won't be able
to extend them any further.

While I'm at it, here's an idea I had a few years ago, never gonna use
personally, go nuts.

==Begin Prior Art==
Peptide nucleic acids fused to a FokI domain would make a great and
probably easier to use alternative to Zinc-finger Nucleases for gene
targeting/excision/repair. They won't be orally available without
PEGylation or something though; the FokI domain will get peptidase'd in
the stomach.

Two separate PNAs targeting 8-15bp each with FokI domains could target
almost any area of the genome for homologous recombination based repair.
You could use it to cut out HIV genomes in infected cells, to remove one
copy of a defective gene in dominant (Long QT 2) or incompletely
dominant (Sickle-Cell Anaemia) conditions by other-copy-mediated repair,
or to insert DNA of your choice.

As far as I know, there's no patent minefield yet in the PNA-protein
fusion area, so it could be what Zinc-Fingers were supposed to be, and
might be in ~15 years. Until then, there's always TALENs as a
locally-transcribed alternative for all the above, if you don't want
something edible.
==End Prior Art==

[Cathal Garvey]

If, *IF* you could guarantee the Telomerase activation was transient,
it'd actually be a great way to poke precancerous lesions into revealing
themselves to the immune system or to other therapies.

Indeed, based on the somewhat extensive research I had to do a few years
back for Cancer Research project, much of the cancer recurrence you see
years after "cure" is actually the re-evolution of cancer from
precancerous cells that escaped the primary tumour really early but hit
the hayflick limit elsewhere in the body or were otherwise contained.
Helping them to temporarily bypass the hayflick limit during
chemotherapy or similar would render them susceptible to treatment.

This being part of a broader hypothesis of mine that "baiting" cancer
will become part of routine therapy within a decade. Also lends credence
to the original hypothesis of homeotherapy* that a little of what causes
something can help treat it: Totally transient "carcinogens" might help
flush out precancerous cells.

-Cathal

*The *real* original Homeotherapy, not this dilution-to-oblivion
bullshit. Homeo = same; Homeotherapy started out AFAIK with the idea
that if you want to treat something minor, you give a little of
something that causes a more severe reaction at full dose- the body
responds to the treatment by "pushing back" and curing the original
minor condition.

--
www.indiebiotech.com
twitter.com/onetruecathal
joindiaspora.com/u/cathalgarvey
PGP Public Key: http://bit.ly/CathalGKey

[Phil]

> Two separate PNAs targeting 8-15bp each with FokI domains could target
> almost any area of the genome for homologous recombination based repair.

The FokI domain part of this was patented in 1990, so the patent has
now expired.

http://www.freepatentsonline.com/4935357.html

[Mac Cowell]

"Fok" yeah!

-- 
Mac Cowell // 775.553.5005 // @100ideas

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[Patrik]

On Oct 19, 2:24 am, Cathal Garvey <cathalgar...@gmail.com> wrote:
> And because they have
> little charge, they should penetrate the cell/nuclear membrane pretty
> easily.

Hm - haven't looked into PNA's much, but I noticed the wikipedia page
had this to say:

"Since the backbone of PNA contains no charged phosphate groups, the
binding between PNA/DNA strands is stronger than between DNA/DNA
strands due to the lack of electrostatic repulsion. Unfortunately,
this also causes it to be rather hydrophobic, which makes it difficult
to deliver to body cells in solution without being flushed out of the
body first.
[...]
Though an unmodified PNA cannot readily cross cell membranes to enter
the cytosol, covalently coupling a cell penetrating peptide to a PNA
can improve cytosolic delivery."

[Yuriy Fazylov]

yeah. this might help

https://www.youtube.com/watch?v=4EOyLM6M_7s

http://www.longecity.org/forum/topic/19921-astragalus-astragaloside-iv/

is anyone still looking into this?

[Yuriy Fazylov]

On Monday, October 6, 2014 9:46:13 PM UTC-4, Yuriy Fazylov wrote:
> yeah. this might help
>
>
> https://www.youtube.com/watch?v=4EOyLM6M_7s

Too bad this site doesn't offer edit post features

[Mega [Andreas Stuermer]]

Aspirin activates telomerase (in epithelial cells) as does estrogen

[Cathal Garvey]

Citation for that? Sounds interesting.
Aspirin is hardly ideal, though. Also a blood thinner. Also a COX1/COX2
inhibitor. Also raises risk of ulcers. A specific telomerase activator
would be nice, although at least Aspirin also reduces incidence of
cancer, which would be a side-effect of specific telo-activation.

On 07/10/14 09:55, Mega [Andreas Stuermer] wrote:
> Aspirin activates telomerase (in epithelial cells) as does estrogen
>

--
Twitter: @onetruecathal, @formabiolabs
Phone: +353876363185
Blog: http://indiebiotech.com
miniLock.io: JjmYYngs7akLZUjkvFkuYdsZ3PyPHSZRBKNm6qTYKZfAM

[Mega [Andreas Stuermer]]

Antonella Farsetti, Annalisa Grasselli, Silvia Bacchetti, Carlo Gaetano, Maurizio C. Capogrossi: The telomerase tale in vascular aging: regulation by estrogens and nitric oxide signaling; Journal of Applied Physiology, January 2009, Vol. 106no. 333-337DOI: 10.1152/japplphysiol.91360.2008

[Mega [Andreas Stuermer]]

It was endothelial cells, sorry. 

On Wednesday, October 19, 2011 11:11:06 AM UTC+2, Cory Geesaman wrote: