LONGECITY

The only possible negative side effect I've seen is what may be a very minor increase in the size of 2 moles. I am not sure, it's hard to tell. I am following this closely and with great curiosity.

I had that as well, they seemed to flare-up then shrink to smaller and flatter than they were originally. But it doesn't seem to work on very old warts which remain unchanged.

Yes, I did a goodle search for "TA-65 moles" a week ago and found your posting about it on another thread here. That's really incredible. Mine also look like a very small "flaring", almost as if you puffed them up slightly with air. That's why I'm finding it so hard to tell if it's a real change. How long were you on TA-65 before they flared, and how long before they started to shrink? Thanks a lot for commenting on this; I was meaning to write back to your previous postings on the subject and ask you about it. BTW I have never taken TA-65/cycloastragenol.

However, I will say that I am extremely happy with the results I've had with Product B. Since September, I have seen substantial improvements in the skin on the palms of my hands and feet and under my eyes. I used to have to clean hair out the drain of my shower every 2 weeks or so. I no longer need to do this, and I have seen some hair regrowth on my previously receding hairline. I've seen a minor improvement in energy, to the point that I've cut my coffee consumption down from 3-4 cups/day to 1-2 cups/day. I've also found that I'm able to operate reasonably well with less sleep.

The only possible negative side effect I've seen is what may be a very minor increase in the size of 2 moles. I am not sure, it's hard to tell. I am following this closely and with great curiosity.

These are nice outcomes, but I wouldn't attribute them to telomere extension. With telomerase induction on the same order at cycloastragenol, I don't think that things would change this quickly. On the other hand, there are a ton of other ingredients in product b with various bioactivities; certainly looks like a CNS stimulant of some sort is on board. I hope the hair regrowth effect is real; maybe a 5-alpha reductase effect?

I agree with you 100% niner. There are too many confounding variables to officially attribute it to any mechanisms involving telomerase. I saw initial changes in the skin on my hands/feet and in my energy levels after about 3 weeks, which I agree is suspiciously fast. Time will tell for sure.

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Yes, I did a goodle search for "TA-65 moles" a week ago and found your posting about it on another thread here. That's really incredible. Mine also look like a very small "flaring", almost as if you puffed them up slightly with air. That's why I'm finding it so hard to tell if it's a real change. How long were you on TA-65 before they flared, and how long before they started to shrink? Thanks a lot for commenting on this; I was meaning to write back to your previous postings on the subject and ask you about it. BTW I have never taken TA-65/cycloastragenol.

I was on Anthony's Cyclo last year really for most of the year cycling it on for a couple of weeks at a time. I was taking 10mg per day. Its a bit hard to remember exactly, but I noticed them starting to flare up after quite a short time after starting cyclo, then they suddenly shrunk and then continued to shrink more slowly there after. I am still on cyclo at the moment and the moles are now completely flat, hardly detectable to finger touch at all.

I doubt the hair growth is anything to do with Alpha 5R because DHT blocking is a big libido trasher and cyclo has completely the opposite effect!

I have other friends on cyclo and it seems after 2-3 weeks they go through a personality change.
A writer friend of mine wrote this to me:

"I don't know about needling less sleep, but...
Sunday I rattled through my neglected to-do list program and started referencing it like I intended.
Monday I was seized by the need to clear my desk surfaces, which had become incredibly congested.
Yesterday I went through my book's contents, stripping away the clutter.
Last night I found myself going through three years of unfiled bills, subscriptions and other kinds of receipt.
Now I just want to get this book out of the way. Is there a pattern here?"

The anecdotal effect that I've seen mentioned by a number of people is vision improvement that was verified by an ophthalmologist. People have reported that their prescription strength got lower, rather than the usual case of getting stronger or staying the same. It's common for presbyopia to accelerate through early middle age, then stabilize, but I've never heard of it receding. They only alternative explanations I can come up with are that this (and possibly other effects) is a non telomere related receptor mediated response, or that the placebo effect is encouraging people to "see better" in the doctors office. The placebo effect strikes me as a bit of a stretch in this case, but it's pretty powerful, so you never know. If anyone reports this on Product B, I'll be impressed.

Ophthalmologists measure visual acuity with a laser based instrument, not with an eyechart. Though they test perceptual ability, the laser tells them what's really going on with the lens. Presbyopia is caused by continued growth and hardening of the lens. It is possible that somehow flexibility is being restored, enabling greater visual acuity but I think it's a stretch without a clearer causal mechanism. The lens material itself is not composed of living cells, and is so poorly supplied with blood, it is difficult for any ingested material to reach the tissues there.

I haven't personally noticed any eyesight improvements on product B, nor have any of my family members who take it. (We've been on it for less than 2 months.)

I did however find the following anecdotal account(s) of eyesight improvements, although as usual you never know how believable because they come from someone selling the product:
http://www.nutrition...ts-testimonial/

Could mechanisms related to accumulation of senescent cells in the eyes with age partially explain why a telomerase inducer would be of benefit? Possibly in my opinion.
The recent Mayo Clinic Nature paper that's generated so much recent buzz goes into specific details on eye tissue and senescence.

Could mechanisms related to accumulation of senescent cells in the eyes with age partially explain why a telomerase inducer would be of benefit? Possibly in my opinion.

I believe it may delay cells from becoming senescent, but just like other ingredients, I doubt it would kill the senescent cells with P16 activity. It appears some other ingredients delay this as well (I am thinking curcumin again), and are cheaper than TA-65 and other ingredients said to be inducers.

http://www.sciencedi...014579311006570

ING1 protein is a tumor suppressor which plays significant roles in multiple cellular activities. p47^ING1a and p33^ING1b are major splice isoforms of ING1 and their roles in senescence need further investigations. Here we studied the functions of ING1 isoforms in cellular senescence and gene regulation, with focus on p16^INK4a. We observe that p33^ING1b protein is the major ING1 isoform expressed in 2BS human diploid fibroblasts. Overexpression of p33^ING1b induces cellular senescence and upregulates p16^INK4a expression in 2BS fibroblasts. p33^ING1b upregulates p16^INK4a transcription. p33^ING1b and p300 bind to the p16^INK4a promoter. p300/CBP-specific inhibitor curcumin can reverse the induction of p16^INK4a by p33^ING1b. These results help to better understand the function of ING1.

In my opinion, inducing telomerase will likely not work regarding the recent senescent cell discovery, which destroys senescent cells exhibiting P16 inducement. Telomerase doesn't appear to do this.

A
Edited by Anthony_Loera, 10 November 2011 - 07:06 PM.

Ophthalmologists measure visual acuity with a laser based instrument, not with an eyechart. Though they test perceptual ability, the laser tells them what's really going on with the lens.

The only way I've ever had it done is with an instrument that I look into while the doctor flips through different lenses, causing the appearance of an image of letters to change. He'll ask me which is clearer, this one?... or this one? Often it's a tossup. Maybe that's old-school technology.

Significantly reducing the percentage of critically short telomeres in the eye should really slow down the build up of new senescent cells in the eye and give the tissue time to clear the existing build up. P16 induced apoptosis is one way, but there are lots of other ways tissue rids itself of senescent cells. This would be a slow process, which might explain why you'd need to be on a telomerase inducer for a long time to see an improvement in eyesight. This is all pure speculation, but seems conceivable to me.

Then there are 2 other effects that might also be at play: Increasing telomere length in the tissue might speed up its ability to clear the senescent cells. And then you may also see some rejuvenation of tissue via increased differentiation and proliferation of stem cell pools in the eye.

visual acuity but I think it's a stretch without a clearer causal mechanism. The lens material itself is not composed of living cells, and is so poorly supplied with blood, it is difficult for any ingested material to reach the tissues there.

I agree.

Louis are you saying that we should use eyedrops?
Because Maxwatt makes a good point. By his statement, it appears that telomerase inducers or curcumin, might be difficult to help remedy visual acuity.

A

visual acuity but I think it's a stretch without a clearer causal mechanism. The lens material itself is not composed of living cells, and is so poorly supplied with blood, it is difficult for any ingested material to reach the tissues there.

I agree.

Louis are you saying that we should use eyedrops?
Because Maxwatt makes a good point. By his statement, it appears that telomerase inducers or curcumin, might be difficult to help remedy visual acuity.

I don't know about curcumin, but vision improvements have been reported by multiple people using cycloastragenol. I think most/all of them were on the higher end of the dosing spectrum. Either they're all making it up or there's a mechanism in there somewhere that we haven't figured out yet. Maybe it's not in the lens; maybe it has something to do with the muscles or other tissues surrounding the lens. Eyedrops are an interesting idea. Speculative, possibly hazardous, but maybe it would work.

Personally, I think the lens epithelium cells may be involved with presbyopia. Epithelium cells in the body tend to express telomerase much more so than other normal cell types, because they need to divide a lot. It's these cells that generate the (non-living) material of the lens. As they senesce, they stop maintaining the lens, and a build up of senescent cells may start to poison the whole epithelium. Without maintenance, the lens itself would degenerate faster. Again, this is all pure speculation. Eye drops might help if the telomerase inducer in the drops could find its way to the epithelium.

I think the ciliary muscles are probably also involved with presbyopia, not just the lens itself. The muscle tissue may then also be the target for a telomerase inducer.

Ophthalmologists measure visual acuity with a laser based instrument, not with an eyechart. Though they test perceptual ability, the laser tells them what's really going on with the lens. Presbyopia is caused by continued growth and hardening of the lens. It is possible that somehow flexibility is being restored, enabling greater visual acuity but I think it's a stretch without a clearer causal mechanism. The lens material itself is not composed of living cells, and is so poorly supplied with blood, it is difficult for any ingested material to reach the tissues there.

>> It is possible that somehow flexibility is being restored, enabling greater visual acuity but I think it's a stretch without a clearer causal mechanism.

I propose that the causal mechanism you're searching for is increased replicative capacity of the lens epithelium cells, due to telomerase induction. This could in principle restore "flexibility" to the lense.

An excellent review article on the lens epithelium can be found here:
http://www.bioscirep...537/0210537.pdf

Quoting from the abstract:

This single layer of cells, in addition to acting as a metabolic engine that sustains the

physiological health of this tissue, also works as a source of stem cells, providing precursor

cells, which through molecular and morphological differentiation give rise to fiber cells.

A telomerase inducer would in principle increase proliferation and differentiation of these stem cells, and keep the "metabolic engine" running by delaying senescence.

Plausible.

I was just reading the sens.org website (this was toward the bottom):
http://sens.org/node/2449

How might the results of this intervention be translated for human rejuvenation therapies?

There is already evidence that senescent cells are targeted by the innate immune system.(24-28) Dr. Judith Campisi, in fact, has found that activating NKG2D receptors on natural killer (NK) cells engage MHC class I chain-related protein A and B (MICA/B) ligands on senescent cells, leading to their NK-induced apopotsis and subsequent clearance.(29) MICA/B ligands are also used to activate tumor cell destruction by NK cells via NKG2G binding, and tumors evolve resistance by several mechanisms to reduce cell-surface MICA abundance;(30) however, the natural selection mechanisms that drive the evolution of such defenses do not apply to growth-arrested cells. Dr. Campisi has found instead that a minority of senescent cells evade destruction by secreting high levels of matrix metalloproteinases (MMPs), which cleave MICA/B ligands and thereby prevent NKG2D binding.(29) This has led to the hypothesis that the great majority of such cells are destroyed over the lifetime by innate immunity, and that the specific senescent cells that do accumulate with aging are precisely those who had variants that allow MMP overexpression, in a kind of "one-off," very temporally-extended kind of selection process. Potentially, a kind of intervention that could overcome this resistance to endogenous clearance mechanisms would allow for the purgation of senescent cells from aging tissues.

So assuming a telomerase activator gingerly activated the immune cells... would a period of having a zinc deficiency contribute to clearing some of the cells out, since the MMP's are dependent on Zinc?

As far as I know, only Cycloastragenol / TA-65 materials have been proven to activate telomerase in immune cells.

A

There is already evidence that senescent cells are targeted by the innate immune system.(24-28) Dr. Judith Campisi, in fact, has found that activating NKG2D receptors on natural killer (NK) cells engage MHC class I chain-related protein A and B (MICA/B) ligands on senescent cells, leading to their NK-induced apopotsis and subsequent clearance.(29) MICA/B ligands are also used to activate tumor cell destruction by NK cells via NKG2G binding, and tumors evolve resistance by several mechanisms to reduce cell-surface MICA abundance;(30) however, the natural selection mechanisms that drive the evolution of such defenses do not apply to growth-arrested cells. Dr. Campisi has found instead that a minority of senescent cells evade destruction by secreting high levels of matrix metalloproteinases (MMPs), which cleave MICA/B ligands and thereby prevent NKG2D binding.(29) This has led to the hypothesis that the great majority of such cells are destroyed over the lifetime by innate immunity, and that the specific senescent cells that do accumulate with aging are precisely those who had variants that allow MMP overexpression, in a kind of "one-off," very temporally-extended kind of selection process. Potentially, a kind of intervention that could overcome this resistance to endogenous clearance mechanisms would allow for the purgation of senescent cells from aging tissues.

So assuming a telomerase activator gingerly activated the immune cells... would a period of having a zinc deficiency contribute to clearing some of the cells out, since the MMP's are dependent on Zinc?

Thanks for that find, Anthony. I don't think that a period of zinc resistance would help in this case, because once the MICA/B ligands are cleaved from the senescent cell, they're gone, and it doesn't matter if the proteases are functioning any longer or not. You'd nee to take a MMP inhibitor all the time, but then that would have all kinds of horrid side effects, since MMPs are needed for tissue remodeling. We'd need to find some surface marker that could be targeted, or find something internal that's critical to senescent cells and not in normal cells that we could interrupt. Another possibility would be something that is differentially toxic, that would preferentially kill senescent cells even if it harmed normal cells somewhat. That would be the cancer chemotherapy approach. For something like that, it would either have to have a huge benefit or not be very harmful. The one thing about such an approach that I like is that we don't need to kill every cell, or even 90%. We could use low levels of drugs in order to minimize toxicities. If we could kill 30-50% of our MMP expressing senescent cells with minimal toxicity, that might be a good therapy.

Woops.. yes after you pointed it out, I read it again and it made sense. I guess I was too excited about the idea, and made a mistake.

If we could kill 30-50% of our MMP expressing senescent cells with minimal toxicity, that might be a good therapy.

I see a ridiculous money maker for cosmetic doctors on this one.

A
Edited by Anthony_Loera, 13 November 2011 - 03:30 AM.

Plausible.

Now any ideas on why on earth moles would shrink in response to a telomerase activator? This one has me completely stumped.

I was thinking the initial flareup is probably just the result of increased cell division, but perhaps it is evidence of an immune response which then ends up eventually shrinking the mole?

Another possibility would be something that is differentially toxic, that would preferentially kill senescent cells even if it harmed normal cells somewhat. That would be the cancer chemotherapy approach. For something like that, it would either have to have a huge benefit or not be very harmful. The one thing about such an approach that I like is that we don't need to kill every cell, or even 90%. We could use low levels of drugs in order to minimize toxicities. If we could kill 30-50% of our MMP expressing senescent cells with minimal toxicity, that might be a good therapy.

See new post in Bioscience section:
http://www.longecity...post__p__485633

It's possible something like this is in the pipeline...

A

The anecdotal effect that I've seen mentioned by a number of people is vision improvement that was verified by an ophthalmologist. People have reported that their prescription strength got lower, rather than the usual case of getting stronger or staying the same. It's common for presbyopia to accelerate through early middle age, then stabilize, but I've never heard of it receding. They only alternative explanations I can come up with are that this (and possibly other effects) is a non telomere related receptor mediated response, or that the placebo effect is encouraging people to "see better" in the doctors office. The placebo effect strikes me as a bit of a stretch in this case, but it's pretty powerful, so you never know. If anyone reports this on Product B, I'll be impressed.

I know you have no reason to believe me, but I started taking Atral Fruit NF a year or so ago. I was not expecting to see any change really. I tend to be skeptical, and the list of supplements I've tried with no noticeable effect is large (not that I doubt they have an effect I just don't feel anything different that I can tell). I was unaware of reports that Cycloastregenol can affect vision so I was shocked when I experienced in improvement ibn my eyesight. The only evidence I have is that I have had eye surgery to correct my vision so I have taken a keen interest in what I can read from a particular distance. I noticed a distinct increase in the distance from which I could read. No real other verification. I would assume that to be susceptible to the placebo effect one would have to know of the effect in order to anticipate it. I get the impression my experience is unusual but not unique. The best theory I can some up with is that maybe the effect is only seen in some people, possibly people like me whose vision isn't perfect to begin with.
Edited by Gern, 04 December 2011 - 09:01 PM.

I certainly believe you. What you're reporting is very consistent with anecdotal accounts of others taking TA-65, cycloastragenol, and product B.

Thanks Louis,

but I do not recommend Product B, as in it's current formulation, does not meet RevGenetics minimum standards which TA-65 and Cyclo have been shown to meet in human immune cells.

Astral Fruit-NF had a few more ingredients other than Cycloastragenol, which (a couple) I believe are not found in Product B, and were used to increase absorption.

Cheers
A
Edited by Anthony_Loera, 06 December 2011 - 05:04 PM.

Anthony,

Are you officially saying product B doesn't activate telomerase enough compared to TA-65 ? is your research/testings over or are you only refering to the eyesight improvement aspect ?

just received product B. I was surprised to see that there is no astragalus extract of any kind in there....

sunshinefrost: Do you still use Product B ? Any positive/negative effects ? Can you tell how do you feel ?

When I first read about Product B I assumed it was intended to be cycled with TA65. And thought it was interesting to put Myrobalan in there wondering if the intent was the minimize any possible telomerase inhibitor effect by the other stuff in the mix. Do they actually intend you to take Product B and TA65 together?

Howard

I now feel reasonably confident in reporting a decrease in the number of gray hairs in my beard since starting product B. At first I thought this was just observer bias, but there's definitely fewer now than before starting, although the difference is fairly minor. I think what's happening is that the grays are falling out gradually and not being replaced as gray. The whole process has been very slow and subtle.

On the negative side, my moles are still "flared" with no signs of decreasing in size (but also no increase).
A few other moles also now seem to be showing this flaring phenomenon.

Thanks Louis,

but I do not recommend Product B, as in it's current formulation, does not meet RevGenetics minimum standards which TA-65 and Cyclo have been shown to meet in human immune cells.

Astral Fruit-NF had a few more ingredients other than Cycloastragenol, which (a couple) I believe are not found in Product B, and were used to increase absorption.

Cheers
A

Anthony, in a previous thread you mentioned that you were planning to publish these results in a peer-reviewed journal.

I think that's an outstanding idea. Your results would be taken seriously that way.

If your experimental methods are sound and product B really doesn't activate telomerase in immune cells, then that's an important result that the scientific community should know about. And if it turns out that there were problems with your tests, the peer reviewers will disallow the paper or other scientists will write into the journal and their letters will be published. It would also prompt others to repeat your tests and it would likely prompt Sierra Sciences to publish their own in vitro results as well. All of these are good things.

It looks like Sierra Sciences is now in the midst of a clinical trial in collaboration with Maria Blasco at Life Length. They are measuring percentage of short telomeres before and after a trial period with product B. It appears their plan is to publish a paper along the lines of the trial run with TA-65. But depending on the length of the trial, it could be 2 years or more before such a paper actually appears in the literature. It would be nice to see some actual published science on this before then.

If your experimental methods are sound and product B really doesn't activate telomerase in immune cells, then that's an important result that the scientific community should know about. And if it turns out that there were problems with your tests, the peer reviewers will disallow the paper or other scientists will write into the journal and their letters will be published. It would also prompt others to repeat your tests and it would likely prompt Sierra Sciences to publish their own in vitro results as well. All of these are good things.

It looks like Sierra Sciences is now in the midst of a clinical trial in collaboration with Maria Blasco at Life Length. They are measuring percentage of short telomeres before and after a trial period with product B. It appears their plan is to publish a paper along the lines of the trial run with TA-65. But depending on the length of the trial, it could be 2 years or more before such a paper actually appears in the literature. It would be nice to see some actual published science on this before then.

I don't know if it will be that easy to get the RevGenetics results published. Assuming that it didn't show activation, then it's a situation of "these guys claim Product B activates telomerase, but it doesn't work in our assay". While that's interesting to us, it's essentially the same as "these guys claim Clorox Bleach activates telomerase, but it doesn't work in our assay."

If Sierra Sciences/Maria Blasco show reasonable activity in their in vivo trial, that would be great, although the first thing that popped into my mind when I read it was "you could sell a lot of Product B in two years...".

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_{I really hope they rush it and it doesn't take 2 years. I think 6 months is plenty if they double the dose to 8caps/day - based on my own results. Two years is just way too long to wait. I've been trying to get my own short telomere load measured so I can track my own progress, but Life Length isn't offering it in the US yet. That is also frustrating me. I think these tests for mean telomere length just aren't going to show much - that's why I haven't bothered. I've been waiting for Life Length to offer their test for percentage of short telomeres.}
Edited by Louis, 08 December 2011 - 08:28 AM.