I sent Aubrey an e-mail, asking him whether or not TA-65 would be an effective way to combat aging. He forwarded my e-mail to a colleague who replied with the following:
Hi Nikolay,
>
> Do you have any thoughts about the 'telomere lengthening' supplement
> sold by this company?
http://www.tasciences.com/> Supposedly the supplement, TA-65, activates telomerase in somatic
> cells. Would this be a practical way to combat aging?
I'm afraid not, for several reasons. In addition to the fact that it's
quite unproven to do what it claims to do even in the very narrow sense
(activating telomerase in people swallowing the capsults), it also
wouldn't do much to affect aging even if it did, and could actually be
dangerous for a specific, very important age-related disease: cancer.
First, we don't yet know that TAT2/TA-65 can lengthen telomeres in
vivo. I don't actually believe that this has actually been reported:
their only published report ( J Immunol. 2008 Nov 15;181(10):7400-6) is
of an in vitro experiment with human CD8+s taken *from* an HIV+ patient,
not in vivo or even ex vivo after oral administration of the compound.
They've shown that when they've mixed the stuff, in a *test tube* , with
white blood cells from HIV patients (whose white blood cells have
abnormally shortened telomeres, because the virus forces them to
replicate those cells which wears the telomeres down), TAT2/TA-65
activates telomerase in those white cells and brings their
pathogen-killing function (again, in a test tube) closer to cells from
normal healthy people.
But this doesn't prove that the same thing would happen to these HIV
patients (let alone normal, healthy people) after swallowing a *pill*
with TA-65: phytochemicals are, notoriously, extensively modified in the
gut and liver by the same enzymes that detoxify various toxins and
drugs, which often either blocks their absorption or drastically changes
their bioactivity once they actually reach the cells of the body through
the circulation. And, moreover, the fact that (broken record! -- *in a
test tube* ) these HIV patient cells have a *more normal* cell-killing
ability; that doesn't show that a person with *normal, healthy* white
cells would get an *even greater* cell-killing capacity (even in a test
tube
) under the same conditions.
This, obviously, in itself dampens enthusiasm, as (from the perspective
of the biogerontology community) does the fact that the patient is HIV+,
and thus has CD8+ cells that are already defective because of the
stressful systemic environment, so that -- even if the effects in vitro
were to translate into a result in vivo -- the *relative* increase in
telomere length, cytokine production, and virus-killing activity may be
of no significance to people with normal T-cell function, or with
age-related impairments unrelated to those in this HIV+ patient.
This leads into the second and broader question of whether activating
telomerase would actually provide any benefits to "normally" aging
people. Since the early excitement raised by the initial discovery of
telomerase in the context of the early, simplistic model of replicative
senescence on which it was superimposed (the "Hayflick limit"), our
understanding of both cellular senescence and its relationship to
organismal senescence has expanded quite a bit. While the popular press
continues to promote the idea that we age because our cells run out the
proliferative capacity by running up against critically-shortened
telomeres, there's very little support in the scientific community today
for either the proposition that cellular senescence is predominantly the
result of telomere erosion, or that replicative arrest per se makes a
major contribution to organismal aging. See:
Hopkin K.
More than a sum of our cells.
Sci Aging Knowledge Environ. 2001 Oct 3;2001(1) : oa4. Review.
PMID: 14602948 [PubMed - indexed for MEDLINE]
Hornsby PJ.
Mouse and human cells versus oxygen.
Sci Aging Knowledge Environ. 2003 Jul 30;2003(30):PE21.
PMID: 12890857 [PubMed - indexed for MEDLINE]
(The above two are intend for the educated layperson; here's one that's
more challenging:
Patil CK, Mian IS, Campisi J.
The thorny path linking cellular senescence to organismal aging.
Mech Ageing Dev. 2005 Oct;126(10):1040-5.
PMID: 16153470 [PubMed - indexed for MEDLINE]
Finally, and most importantly, even if it works systemically after oral
administration, and even if it did provide benefits to at least some
aspects of aging, systemic delivery of a compound that (putatively)
activates telomerase makes a lot of people (myself and Dr. de Grey
included) very nervous, for the simple reason that telomerase activation
could open up the proliferative barrier for preneoplastic cells to push
over the limit imposed by 'crisis' and programmed senescence and acquire
the additional mutation(s) required to become fully-fledged malignant
cancer cells. Part of the reason we have telomeres wearing down in our
cells in the first place is to prevent runaway cell proliferation -- in
other words, cancer. In fact, cancer cells can't survive without
acquiring mutations that allow them to keep lengthening their telomeres
as they divide furiously, and they most often do this exactly by
activating telomerase! These companies point to studies that show that
activating telomerase doesn't *cause* the cells to become cancerous, but
that's not the point: doing so gives *precancerous* cells the
*opportunity* to keep replicating themselves, acquiring new mutations
and eventually becoming full-blown cancers, by taking off the cell's
ultimate braking system for cell division. Bypassing this strict control
by a drug or supplement is really asking for trouble.
More on this here:
http://www.mfoundati...hread.php?t=437http://www.mfoundati...e...1243&page=2http://www.mfoundati...e...1243&page=2> P.S. Happy new year.
And to you -- and many, many more! And , if you're ready to help us to
increase your odds of enjoying those additional years by hastening
progress in SENS science, we have quite a few listed here:
http://sens.org/inde...donations_otherAlso, you can pick up a copy of Aubrey's and my book (link above) and,
after having read it for your own further understanding, get the word
out by passing your copy around to others you know, and/or by donating
it to a library, and/or by picking up extra copies for the latter 2
purposes.
And (naked plug!) remember that you can help to ensure that real
age-reversing biotechnology becomes available as soon as possible,
alleviating the most age-related suffering and death, by making a
donation to support SENS research:
http://sens.org/inde...onations_donateI leave it to you to choose how you will take on the moral and
scientific challenge of biological aging. However you proceed: live long
-- live young!
-Michael
