For a review of small molecule telomerase activators and inhibitors, see
Supplemental Notes 3 - Anti-Aging Medicine, and also
http://greenwood.s5.com/longevity.html#(7) for a general discussion of the problem
of telomerase activation and inhibition in life extension therapy.
I was pleased to get the first
TA Sciences newsletters in 2007 from Greta Blackburn specifying
a mean telomere length increase of 230 base pairs in granulocytes (an immune cell that circulates in the blood)
after 3 months of treatment at 5 mg/day of TA-65, which I suspect is cycloastragenol based
on Geron patent literature. Note that
TA Sciences, using 5 mg/day TA-65 (cycloastragenol?)
on a 3-month-on, 3-month-off cycle for a year measures 460 bp/year telomere growth in blood granulocytes,
while aging normally subtracts about 50 bp/year, so that on TA-65 the telomere biotimer moves backwards in time
about 9 times as fast as it goes forwards when "aging".
Thus one can devise a treatment strategy that nets about a decade of life for each year invested, as far as numbers of available cell divisions are concerned.
Geron published its milestone document
Compositions and Methods for Increasing Telomerase Activity in 2005. It is online at
http://v3.espacenet.com/origdoc?DB=EPODOC&...530ecb46d14e48b .
I found it by doing extensive searching in the Spring of 2007 after visiting the
TA Sciences site,
which mentioned that TA-65 was obtained from astragalus extract. Several other groups were working on telomerase
activators, such as the Biogerontology group in St. Petersburg that discovered the pineal gland bioregulator associated
with telomere homeostasis, epitalon, or Ala-Glu-Asp-Gly. By now I have listed about 30 telomerase activators and
perhaps 25 telomerase inhibitors, and have concluded that cyclic telomerase activation similar to the Patton Protocol
might be implemented in two-week pulses, two weeks on telomerase activators without telomerase inhibitors,
and subsequently two weeks without telomerase activators but including telomerase inhibitors like resveratrol,
quercetin, curcumin, vitamin E, green tea, garlic, and fish oil. Some of these telomerase inhibitors have desirable
properties that we don't want to miss out on, so a tight cycle has some advantages. I note that telomerase
activators keep telomerase turned on from 24 hours after application to up to 75 hours after stopping activation.
I have been trying to use 5 mg/day of astragalosides from GAIA Astragalus extract in experiments,
and have been considering using 10 mg/day in two 5 mg doses, since 5 mg of astragalosides conveys a palpable
tingle or turn-on when taken without breakfast or just before bedtime. TA-65 would probably be superior, because
it is the smallest astragaloside molecule that activates telomerase. Astragaloside iv may evidently also be used at 50-100 mg/day,
and I note that chitin makes astragaloside iv in astragalus extract more bioavailable. Of course, controlled
experiments need to be done to get a feel for the results that can be obtained with commercially available
telomerase activators, and
TA Sciences has made a great contribution in this direction.
Since March 2009 I have substituted 6 x 200 mg/day Solaray Astragalus Root Extract (1200 mg/day) in order to approach
5 mg/day astragalosides. This dose satisfies my toxicology checks and initial calculations showed that 5 mg/day astragalosides
might be attained with this prescription. Otherwise, I use 5 mg/day arginine with 1 mg/day citrulline with exercise to elevate my
nitric oxide levels as recommended by nobelist Louis B. Ignarro in his book NO More Heart Disease. Nitric Oxide
produces telomerase activation in endothelial cells lining arteries according to separate papers by Vasa and Hayashi,
helping to stave off atherosclerotic plaques and other undesirable phenomena associated with replicative senescence
in endothelial cells, refreshing the vascular endothelium with telomeric DNA repair.
