2189 replies to this topic

[hav]

1. There's no clear cut answer to that, I don't think anybody has measure telomere on the amounts you proposed to know for sure which one is more effective. In my opinion, whatever you end up doing take either Cyclo or TA65 and don't bother with AIV. Cycloastregenol is by far the most studied and proven substance.

Actually, a user on this site has done repeated telomere length measurements after sequentially using Cycloastragenol, Astragaloside IV, and Standardized Astragalus extract. Here's his post from Nov 2011 in its entirety with back links to posts of previous test results. Granted, its anecdotal, overlapped use of other supplements like Ginkgo Biloba, and didn't specifically include the branded product TA65, but it is a measured result that includes TA65's known components...

It’s time for one of my longer posts. I have now got the results from my latest FLOW-Fish test after using "Standardised Astragalus Root Extract" (mostly) for eleven months. If someone thinks this post looks a lot like the one I made in December last year, this is because I’m repeating a lot of the results from that post.

For comparison I've got data from four earlier tests.

• Baseline Test
• After 6 months on Astragaloside IV
• After 6 months on Cycloastragenol
• After 6 months on "Standardised Astragalus Root Extract"

I have now made another test after 11 months on "Standardised Astragalus Root Extract"

In order to not repeat to many of my results you can look at the details of the data from these tests in post #787 and post #1077. In post #1073 you can see the details on the execution of my last test of 6 months on "Standardized Astragalus Root Extract". For all tests, I had the lab analyze the Standard Deviation. This cost more money but ought to make the numbers slightly more reliable.

SUMMARY OF COLLECTED DATA
Astragaloside IV
6 months on AIV and Gingko Biloba + 3 last months on Orlistat rendered the following changes from my baseline values:
Lymphocytes: 7.5-7.0 = reduction of 0.5 kb
Granulocytes: 9.1-7.4 = reduction of 1.7 kb
Naive T-cells: 8.3-7.9 = reduction of 0.4 kb
Memory T-cells: 6.3-5.6 = reduction of 0.7 kb
B cells: 8.2-8.1 = reduction of 0.1 kb
NK cells: 4.5-4.0 = reduction of 0.5 kb

When using Astragaloside IV the Standard Deviations changed from
Lymphocytes: 0.6 to 0
Granulocytes: 1.2 to 0
Naive T-cells: 0.4 to 0
Memory T-cells: 0.7 to 0
B cells: 0.7 to 0
NK cells: 0.7 to 0

Cycloastragenol
6 months on Cycloastragenol (including Chitosan) and Gingko Biloba and Orlistat rendered the following changes from the last period.
Lymphocytes: 7.0-7.0 = No change
Granulocytes: 7.4-7.3 = reduction of 0.1 kb
Naive T-cells: 7.9-7.9 = No change
Memory T-cells: 5.6-5.7 = Increase of 0.1 kb
B cells: 8.1-8.2 = Increase 0.1 kb
NK cells: 4.0-4.1 = Increase of 0.1 kb

When using Cycloastragenol the Standard Deviations changed from
Lymphocytes: 0 to 0.2
Granulocytes: Still 0
Naive T-cells: 0 to 0.3
Memory T-cells: 0 to 0.2
B cells: 0 to 0.2
NK cells: 0 to 0.3

"Standardised Astragalus Root Extract", 6 months
6 months on Standardised Astragalus Root Powdered Extract (1mg [0.5%] triterpene glycolides) 225mg, Raw Astragalus Root Powder 250mg, Gingko Biloba, Orlistat (phasing out), "Adidas miCoach Get Fit Stay Fit - Level 4" (3-4 months) and Meditation (3-4 months) rendered the following changes from the last period.

Lymphocytes: 7.0-6.9 = reduction of 0.1 kb
Granulocytes: 7.3-7.6 =Increase of 0.3 kb
Naive T-cells: 7.9-8.1 = Increase of 0.2 kb
Memory T-cells: 5.7-5.8 = Increase of 0.1 kb
B cells: 8.2-8.2 = No change
NK cells: 4.1-5.9 = Increase of 1.8 kb

When using "Standardised Astragalus Root Extract" the Standard Deviations changed from…
Lymphocytes: 0.2 to 0.0
Granulocytes: 0 to 0.1
Naive T-cells: 0 .3 to 0.0
Memory T-cells: 0.2 to 0.0
B cells: 0.2 to 0.0
NK cells: 0.3 to 0.2

"Standardised Astragalus Root Extract", 11 months
During 11 months I have been taken the following supplements and done the following activities.

• 1 month, trying to take Cycloastragenol 10mg/day but having to give it up (see earlier posts).
• 10 months on Standardised Astragalus Root Powdered Extract (1mg [0.5%] triterpene glycolides) 225mg, Raw Astragalus Root Powder 250mg, taking one pill in the morning and one during late afternoon,
• 11 months on Gingko Biloba, 1 pill around lunchtime
• Orlistat, on and off during the period,
• "Adidas miCoach Get Fit Stay Fit - Level 5, 30 minutes", using cross trainer for 20 minutes and a rowing machine for 10 minutes, two times per week,
• Meditation during working days, unfortunately circumstances did not make it possible to meditate more than about three days per week (60% of target),
• During the last five months, been using Minoxidil (50mg/ml) for extended periods,
• Had some weeks when I used LCHF (Low Carb High Fat) or GI-diet.

This rendered the following changes from the last period.

Lymphocytes: 6.9 --> 7.2= increase of 0.3 kb (0.2kb increase the last 18 months)
Granulocytes: 7.6 --> 7.9 =Increase of 0.3 kb (0.6kb increase the last 18 months)
Naive T-cells: 8.1 --> 8.4 = Increase of 0.3 kb (0.5kb increase the last 18 months)
Memory T-cells: 5.8 --> 6.2 = Increase of 0.4 kb (0.5kb increase the last 18 months)
B cells: 8.2 --> 8.4 = increase of 0.2 kb (0.3kb increase the last 18 months)
NK cells: 5.9 --> 5.3 = decrease of 0.6 kb (1.2kb increase the last 18 months)

When using "Standardised Astragalus Root Extract" for 11 (actually 10) months the Standard Deviations changed from
Lymphocytes: 0.0 to 0.3
Granulocytes: 0.1 to 0.3
Naive T-cells: 0.0 to 0.2
Memory T-cells: 0.0 to 0.2
B cells: 0.0 to 0.2
NK cells: 0.2 to 0.1

ANALYSIS/DISCUSSION
Using Astragaloside IV had a quite large negative effect on the telomere lengths. All of the telomeres in the measured cell types decreased in length. Several of the changes were quite large and well outside the possible fault limits of the test. Based on these results and the similar results Anthony had, I would hesitate to recommend anyone from taking Astragaloside IV as a supplement.


Using Cycloastragenol had a more neutral result. The changes were within the fault limits of the test, but at least 75% of the cell types which showed any change at all showed a slight increase in telomere length. I'm still waiting to see the results Anthony got from his test. If they are posted in this thread I must have missed them.


Using "Standardised Astragalus Root Extract" for six months (+ physical training, meditation, less work, gingko biloba, orlistat and LCHF ) had a more interesting result. The median telomere length of my NK cells increased in length by a whopping 1 800 base pairs. This is an increase with 44 percent and well outside the error margin of the test!

I think the changes in MTL for the other types of cells where within the error margin of the test, but personally I think it looks better to have most of them on the plus side than on the minus side. From a subjective point of view I'm especially pleased to see that the potential lengthening of the MTL of the granulocytes where close to being outside the error margin of the test, since they got kind of slaughtered when I used Astragaloside IV.


Using "Standardised Astragalus Root Extract" for 11 months (+ physical training, meditation, unfortunately much more work (and less sleep), gingko biloba, orlistat and LCHF and some minoxidil) generated possible positive results for all cell types except the NK-cells.

Last year the lab estimated their margin of error for these tests to 0.3 kb for lymphocytes and 0.5 kb for granulocytes and the error for the other subpopulations to be in the same range, 0.3 – 0.5 kb. This makes it likely that there has actually been an increase in telomere lengths for the Granulocytes, the Naive T-cells and the Memory T-cells over the last 18 months. Unfortunately it also makes it likely that the telomeres of the NK-cells have decreased in length during the last 11 months.

Some speculations on the results
The positive effects “in vivo” might possible (or not) be attributed to the Standardised Astragalus extract, but it doesn’t necessarily mean that these effects can be found “in vitro”. There might as well be one or several compounds in Astragalus (or the other stuff I took) which affect some part in the body which in turn affect telomere maintenance.

My guess is that my NK-cells are very sensitive to working too much and sleeping too little (due to my alarm clock, not the regimen in itself). I did notice my weight go up during the period, and this is usually related to stress. Maybe I need to prioritize to actually meditate five times per week instead of “about” three. I’m still waiting for my cortisol results. Maybe they can cast some light on the subject. This behavior would however be consistent with my baseline telomere test which I took from the beginning. I had been taking Astragalus (mostly Standardized) before the baseline test (see earlier posts), had a huge amount of stress for a long time (see earlier uploaded cortisol tests), but all telomere results were pretty good except for the NK-cells. And the cortisol tests I had been doing previously where quite bad. At that time I did no meditation and very little training.

With regards to sleep and what I’ve been reading in other posts lately I’m a bit skeptical of people thinking “sleeping less” each night might be a positive effect from a regimen, whether it be Cycloastragenol, Product B, Astragaloside IV or something else. During sleep the body performs a lot of maintenance activities which might have a postitive effect on the immune system. Without actual data on the effects on the immune system it can as well be a negative effect to have to little sleep.

As a side note, I did not notice any change what so ever in hair growth during my last six + eleven months using Standardised Astragalus extract, except the last five months when I started to use minoxidil as well. The “fine white down”, which kind of grows “beneath” the real hair, got a bit more pronounced. No colour yet, though.

FUTURE TESTS
I still have 18 months’ supply left of Cycloastragenol and don’t know if I’ll use it or just throw it away. Then there’s Product B. Or maybe I’ll keep on using Standardized Astragalus extract. I haven’t decided yet.

TEST RESULTS I'M STILL WAITING FOR
Cortisol, DHEA, Testosterone and Melatonin. I have the usual health check numbers but currently not the time to put them on the site. Nothing much to see there, though, I think. The amount of numbers to keep track of have unfortunately started to grow somewhat unmanageable.

Edit: Added links to earlier posts -niner

I've been sticking with a 70% Standardized Astragalus extract myself in favor of Cyclo and AS4 ever since seeing this.

Howard

Edited by hav, 09 July 2013 - 08:24 PM.

[marcobjj]

read again the part where I say " I don't think anybody has measure telomere on the amounts you proposed to know for sure which one is more effective"

I've been sticking with a 70% Standardized Astragalus extract myself in favor of Cyclo and AS4 ever since seeing this.

I think it's a bad idea to base your suplementation on a N=1 experiment when all the evidence (read previous page) points to Cycloastragenol being the only proven telomerase activator available.

Edited by marcobjj, 09 July 2013 - 10:38 PM.

[hav]

I think it's a bad idea to base your suplementation on a N=1 experiment when all the evidence (read previous page) points to Cycloastragenol being the only proven telomerase activator available.

Fair enough, as a general principle.

The Maria Blasco study is the only in vivo study I know of. It dealt with TA65 specifically, used mice, not humans, did show a telomere length increase, no increased incidence of cancer, improved health throughout life... but no increase in longevity.

The telomerase activator TA-65 elongates short telomeres and increases health span of adult old mice without increasing cancer incidence

TA-65 intake does not impact on mean or maximum longevity of female mice
Analysis of the Kaplan–Meier survival curves of control vs. TA-65-treated female mice demonstrated no significant effects of TA-65 intake on survival (Fig. 6A,B). Accordingly, TA-65 administration for 4 months did not change statistically the mean or maximal lifespan of female mice under our experimental conditions

I think this is the strongest study for cycloastragenol but unfortunately mice seem to already have long telomeres and didn't show improved longevity. So Greenpower's longer term N=1 may be a better indicator with regard to humans. But you are absolutely right about N=1 being less than optimal. We need more. The Blasco study just isn't strong evidence to the contrary with regard to humans. And we don't know how Astragalus extract or even water would have fared as a control because she only compared TA65 to DMSO.

Howard

[niner]

The Maria Blasco study is the only in vivo study I know of. It dealt with TA65 specifically, used mice, not humans, did show a telomere length increase, no increased incidence of cancer, improved health throughout life... but no increase in longevity.

The telomerase activator TA-65 elongates short telomeres and increases health span of adult old mice without increasing cancer incidence

TA-65 intake does not impact on mean or maximum longevity of female mice
Analysis of the Kaplan–Meier survival curves of control vs. TA-65-treated female mice demonstrated no significant effects of TA-65 intake on survival (Fig. 6A,B). Accordingly, TA-65 administration for 4 months did not change statistically the mean or maximal lifespan of female mice under our experimental conditions

I think this is the strongest study for cycloastragenol but unfortunately mice seem to already have long telomeres and didn't show improved longevity. So Greenpower's longer term N=1 may be a better indicator with regard to humans. But you are absolutely right about N=1 being less than optimal. We need more. The Blasco study just isn't strong evidence to the contrary with regard to humans. And we don't know how Astragalus extract or even water would have fared as a control because she only compared TA65 to DMSO.

But... Mice have enormously long telomeres, and express telomerase all over the place, so wouldn't this be irrelevant? Maria Blasco is pretty good, or so I thought, so this is a puzzlement. I think Greenpower might have been misled by looking at average lengths rather than percentages of critically short telomeres. My understanding is that telomerase does not efficiently lengthen telomeres unless they are shorter than a particular critical length.

[niner]

"Hi

Apologies for the delay in replying to you. I have consulted our product formulators, and they have told me that BioSpan has 15mg of Cycloastragenol per capsule.

Please let me know if there's anything else I can help you with.

Kind regards"


I don't believe it.

I don't either. This particular company has a long history of internet claims that seem to be in contravention of fact, so I would take what they say with a large grain of salt.

[marcobjj]

I think it's a bad idea to base your suplementation on a N=1 experiment when all the evidence (read previous page) points to Cycloastragenol being the only proven telomerase activator available.

Fair enough, as a general principle.

The Maria Blasco study is the only in vivo study I know of. It dealt with TA65 specifically, used mice, not humans, did show a telomere length increase, no increased incidence of cancer, improved health throughout life... but no increase in longevity.

The telomerase activator TA-65 elongates short telomeres and increases health span of adult old mice without increasing cancer incidence

TA-65 intake does not impact on mean or maximum longevity of female mice
Analysis of the Kaplan–Meier survival curves of control vs. TA-65-treated female mice demonstrated no significant effects of TA-65 intake on survival (Fig. 6A,B). Accordingly, TA-65 administration for 4 months did not change statistically the mean or maximal lifespan of female mice under our experimental conditions

I think this is the strongest study for cycloastragenol but unfortunately mice seem to already have long telomeres and didn't show improved longevity. So Greenpower's longer term N=1 may be a better indicator with regard to humans. But you are absolutely right about N=1 being less than optimal. We need more. The Blasco study just isn't strong evidence to the contrary with regard to humans. And we don't know how Astragalus extract or even water would have fared as a control because she only compared TA65 to DMSO.

Howard

check out this lecture by Bill Andrews:



and here are the results of 12 subjects in his experiment using TA65 for an year, before and after:

Edited by marcobjj, 10 July 2013 - 04:16 AM.

[marcobjj]

[hav]

check out this lecture by Bill Andrews:



and here are the results of 12 subjects in his experiment using TA65 for an year, before and after:

Thanks, marcobjj. I really enjoyed the Dr Andrews presentation. Very informative. I particularly liked the mention of cats and dogs which I enthusiastically join in with.

I also noticed the video included the graphic you posted above which, together with what Dr Andrews said about it, indicates that a clinical human study has indeed been performed... and that 10 out of 12 (or 13?) human subjects showed an in vivo increase in some measure of telomere length after taking TA65 for 1 year. See: YouTube Video at 1:20:47.

But here's the paper... and I'm confused (emphasis added by me).
A Natural Product Telomerase Activator As Part of a Health Maintenance Program

The most striking in vivo effects were declines in the percent senescent cytotoxic (CD8⁺/CD28⁻) T cells (1.5, 4.4, 8.6, and 7.5% at 3, 6, 9, and 12 months, respectively; p=not significant [N.S.], 0.018, 0.0024, 0.0062) and natural killer cells at 6 and 12 months (p=0.028 and 0.00013, respectively)...

In a subset of subjects, the distribution of telomere lengths in leukocytes at baseline and 12 months was measured. Although mean telomere length did not increase, there was a significant reduction in the percent short (<4kbp) telomeres (p=0.037)...

We report results for all evaluable subjects who completed 12 months of the protocol by June, 2009. The number of subjects at 3, 6, 9, and 12 months for most tests was 43, 59, 27, and 37, respectively. The age and gender frequencies of the subset at each time point were similar to those of the total baseline population (n=114; 63±12 years, 72% male).

... Did they cherry-pick their data for the Figure 3 charts? Also, their methods section says this suggesting they are reporting a combination of in vitro and in vivo analysis:

In brief, telomerase activity was measured in actively growing cells incubated for 24–48h with TA-65^® in the vehicle (dimethylsulfoxide [DMSO] at 1% vol/vol [keratinocyte culture] or 0.5% [fibroblasts]) versus vehicle alone. Measurements were typically made at 5–10 population doublings (PD) (keratinocytes) or 30–40PD (fibroblasts).

Also no mention of controls, except in the cultures mentioned above, or any mention of randomization except this:

Controlled randomized trials are planned to assess TA-65^®-specific effects in humans.

Looking forward to seeing those results.

Howard

Edited by hav, 10 July 2013 - 06:07 PM.

[DorianGrey]

Strange result:

I took a look this time at the figure with the gel http://www.ncbi.nlm....5570/figure/f1/
It is interesting that the activation at 0.032uM is 2.5fold, at 0.1umM (3 times higher concentration) 3fold or accounting for the error bar almost unchanged and then goes down again. So, the values for 0.032uM and 0.32uM result in the same telomerase activation and lower values bring down the activation further until there is no activation.
It's an interesting finding because I had expected dose proportionality until a steady-state is reached, not a counteracting effect at high concentrations.

[marcobjj]

10 out of 12 (or 11 out of 13 in the graph) showed a reduction in the number of critically short telomeres after 1 year of taking TA65. 6 out of 13 also showed increased mean telomere length.

In brief, telomerase activity was measured in actively growing cells incubated for 24–48h with TA-65^® in the vehicle (dimethylsulfoxide [DMSO] at 1% vol/vol [keratinocyte culture] or 0.5% [fibroblasts]) versus vehicle alone. Measurements were typically made at 5–10 population doublings (PD) (keratinocytes) or 30–40PD (fibroblasts).

they are citing a different study, check the reference:

http://www.ncbi.nlm....PMC3045570/#B39

Edited by marcobjj, 10 July 2013 - 09:42 PM.

[hav]

10 out of 12 (or 11 out of 13 in the graph) showed a reduction in the number of critically short telomeres after 1 year of taking TA65. 6 out of 13 also showed increased mean telomere length.

In brief, telomerase activity was measured in actively growing cells incubated for 24–48h with TA-65^® in the vehicle (dimethylsulfoxide [DMSO] at 1% vol/vol [keratinocyte culture] or 0.5% [fibroblasts]) versus vehicle alone. Measurements were typically made at 5–10 population doublings (PD) (keratinocytes) or 30–40PD (fibroblasts).

they are citing a different study, check the reference:

http://www.ncbi.nlm....PMC3045570/#B39

Just reread the Method of Action section under Results and I think you're right. Kind of a confusing presentation, however. But I guess it makes sense in light of the Statistics section right before it which states:

Data from this study were collected primarily as a hypothesis-generating exercise because subjects were not participating in a controlled prospective study, and statistical analyses were not formally defined a priori.

But I think this highlights a potential misleading aspect of Dr Andrews presentations when he presents data like this as actually proving anything or being more than "a hypothesis-generating exercise". I've heard him do it in his Product B pitches concerning robotic scan assays whose only really valid function is to identify promising candidates for probative research to see if they actually lengthen telomeres or lifespans as predicted. Same for his patent applications which might make them easy targets. I guess its a grey area if he's trying to raise money to fund the real research but less so when the same pitch is used to sell something like TA65 or Product B to consumers. I like and respect him allot but I think this aspect of his presentations lend themselves to misuse. Which seems like the intent in this case given that he made it to an Independent Pharmacy association interested primarily in consumer sales and then posted it on YouTube apparently targeting the general population.

Howard

[GreenPower]

The Maria Blasco study is the only in vivo study I know of. It dealt with TA65 specifically, used mice, not humans, did show a telomere length increase, no increased incidence of cancer, improved health throughout life... but no increase in longevity.

The telomerase activator TA-65 elongates short telomeres and increases health span of adult old mice without increasing cancer incidence

TA-65 intake does not impact on mean or maximum longevity of female mice
Analysis of the Kaplan–Meier survival curves of control vs. TA-65-treated female mice demonstrated no significant effects of TA-65 intake on survival (Fig. 6A,B). Accordingly, TA-65 administration for 4 months did not change statistically the mean or maximal lifespan of female mice under our experimental conditions

I think this is the strongest study for cycloastragenol but unfortunately mice seem to already have long telomeres and didn't show improved longevity. So Greenpower's longer term N=1 may be a better indicator with regard to humans. But you are absolutely right about N=1 being less than optimal. We need more. The Blasco study just isn't strong evidence to the contrary with regard to humans. And we don't know how Astragalus extract or even water would have fared as a control because she only compared TA65 to DMSO.

But... Mice have enormously long telomeres, and express telomerase all over the place, so wouldn't this be irrelevant? Maria Blasco is pretty good, or so I thought, so this is a puzzlement. I think Greenpower might have been misled by looking at average lengths rather than percentages of critically short telomeres. My understanding is that telomerase does not efficiently lengthen telomeres unless they are shorter than a particular critical length.

Personally I think that the results with "percentages of critically short telomeres" sounds more like a new hypothesis they made up from available data when all results showed that their test objective to prove they could lengthen the test subjects average telomere lengths failed. Like hav I'm also a bit sceptical to this paper because they don't seem to show the results for all the individual test subjects.

In a week or so I will have the time to present the data from my personal n=1 test from the beginning of the year (St. Astragalus/Gingko and Resveratrol periods), but they weren't that revolutionary. Might be that stress/cortisol must be avoided to get good test results. I therefore don't expect too much of the tests I will do now on Monday for my current half year regimen (St. Astragalus/Gingko and Resveratrol only when training) either. It will most likely serve best as a new "baseline" for the next test run.

However, I've got a somewhat unique opportunity to remove about all stress/cortisol for the next half year. I therefore think the next test period will be more interesting. I'm just thinking about what to include in the regimen.

I see that Anthony just added a new Astragalus based product called AT-90 to his product range. It would seem to be a 200mg ordinary Astragalus extract but with 90:1 purity (whatever this actually mean) which they have micronized to the average size of 1-3 microns. Any thoughts on this product?

[Turnbuckle]

I see that Anthony just added a new Astragalus based product called AT-90 to his product range. It would seem to be a 200mg ordinary Astragalus extract but with 90:1 purity (whatever this actually mean) which they have micronized to the average size of 1-3 microns. Any thoughts on this product?

90:1 generally means the yield ratio of extraction, where 90 grams of herb yields 1 gram of extract. And hopefully the component you want is in the one gram and not in the 89 grams you discard. He says he tested a 25:1 and 50:1 extraction [which he calls purity] and it failed to "activate DNA Repair processes," but with a 90: extraction, it did. What that means he doesn't say, though if if was anything like some of his previous work, it was a n=1 trial on himself.

So I would say, with no more information than this, AT-90 looks like a waste of money.

Edited by Turnbuckle, 15 August 2013 - 09:44 AM.

[hav]

I see that Anthony just added a new Astragalus based product called AT-90 to his product range. It would seem to be a 200mg ordinary Astragalus extract but with 90:1 purity (whatever this actually mean) which they have micronized to the average size of 1-3 microns. Any thoughts on this product?

90:1 generally means the yield ratio of extraction, where 90 grams of herb yields 1 gram of extract. And hopefully the component you want is in the one gram and not in the 89 grams you discard. He says he tested a 25:1 and 50:1 extraction [which he calls purity] and it failed to "activate DNA Repair processes," but with a 90: extraction, it did. What that means he doesn't say, though if if was anything like some of his previous work, it was a n=1 trial on himself.

So I would say, with no more information than this, AT-90 looks like a waste of money.

My guess is that the 90:1 extract is similar to an extract designed to maximize cycloastragenol but they're not telling us what the cycloastragenol content actually is. Also noticed on the RevGenetics web site that reference was made to a study they did using the same methods as the UCLA TAT2 (cycloastragenol) in vitro study... which would in my opinion suffer from the same problem as that study...

Cells were treated with TAT2 (1 μM) or DMSO (0.1%) every 48 h for 12 days, at which point cells were harvested for TRAP assay.

...measuring telomere lengthening against DMSO as the only control. This study finds DMSO is a telomerase inhibitor:

Dimethyl sulfoxide (DMSO) causes a reversible inhibition of telomerase activity in a Burkitt lymphoma cell line

I suspect the UCLA study method would get a more valid measurement using DMSO as both a vehicle and a control.

Howard

[free10]

I see that Anthony just added a new Astragalus based product called AT-90 to his product range. It would seem to be a 200mg ordinary Astragalus extract but with 90:1 purity (whatever this actually mean) which they have micronized to the average size of 1-3 microns. Any thoughts on this product?

90:1 generally means the yield ratio of extraction, where 90 grams of herb yields 1 gram of extract. And hopefully the component you want is in the one gram and not in the 89 grams you discard. He says he tested a 25:1 and 50:1 extraction [which he calls purity] and it failed to "activate DNA Repair processes," but with a 90: extraction, it did. What that means he doesn't say, though if if was anything like some of his previous work, it was a n=1 trial on himself.

So I would say, with no more information than this, AT-90 looks like a waste of money.

My guess is that the 90:1 extract is similar to an extract designed to maximize cycloastragenol but they're not telling us what the cycloastragenol content actually is. Also noticed on the RevGenetics web site that reference was made to a study they did using the same methods as the UCLA TAT2 (cycloastragenol) in vitro study... which would in my opinion suffer from the same problem as that study...

Cells were treated with TAT2 (1 μM) or DMSO (0.1%) every 48 h for 12 days, at which point cells were harvested for TRAP assay.

...measuring telomere lengthening against DMSO as the only control. This study finds DMSO is a telomerase inhibitor:

Dimethyl sulfoxide (DMSO) causes a reversible inhibition of telomerase activity in a Burkitt lymphoma cell line

I suspect the UCLA study method would get a more valid measurement using DMSO as both a vehicle and a control.

Howard

Certain chemicals seem to inhibit telomerase or telomere length in cancers, but not in regular cells and this might be the case with DMSO.

[hav]

Certain chemicals seem to inhibit telomerase or telomere length in cancers, but not in regular cells and this might be the case with DMSO.

I think they attribute the DMSO telomerase inhibition to DMSO-induced growth arrest or lengthening of the G0/G1 phases while reducing the S-phase period during cell division. Here are other studies finding a similar growth arrest effect in hamster ovary cells as well as fibroblasts from goldfish, canines, tigers, and bears. Looks like the technique involves treating cells with DMSO for repeated short periods each followed by a wash out and recovery period to keep it from sending the cells into apoptosis.

Here's another interesting one that involved using a synthetic retinoid (HPR) dissolved in DMSO on human epithelial cells from non-cancerous mammary tissue:
http://www.ncbi.nlm....pubmed/10069458

A 24 h treatment with cytostatic 400 nM HPR produced a 25% increase (P = 0.01) in G0/G1 phase, and a 36% decrease (P = 0.01) in S phase of the cell cycle. HPR treatment also induced a 10-fold increase (P = 0.02) in the sub-G0 (apoptotic) peak that was down-regulated in the presence of the antioxidant N-acetyl-L-cysteine.

None of those other DMSO studies above measured telomerase, however, so DMSO telomerase inhibition found in that Raji cell study pretty much hinges on attributing telomerase activation to the G1/S-phase transition of cell division. But I was able to find a non-DMSO study of human dental follicle cells that seems to support the same idea.

Howard

Edited by hav, 15 August 2013 - 06:50 PM.

[GreenPower]

I asked them for some more information on the components of AT-90 and got the following answer:
"The components in the product are proprietary, however we have reduced the iron content dramatically which has presented an issue in the past for those that have taken large amounts of Astragalus for the purposes of DNA Repair. The product has also been micronized to 1-3 microns to achieve high absorption (Something that no other company does for Astragalus compound)."

So whatever compounds they have standardized the extract on, at least iron is not among them.

[GreenPower]

The root powder of the herb; more nutrients, more of everything, carbs, protein, but less ratio of certain compounds. It will be a tad bit of a different effect. I've always used the extracts, minus a few times.

From this thread:

Remember guys:

The difference is that regular astragalus does not usually have a high amount of Astragaloside IV. Here are the amounts of astragalus and the amount of astragaloside iv contained in these amounts:

If we calculate astragaloside iv amount in these astragulus dosages it is interesting that there is not very much in it:
9 grams of Astragalus = 14.4mg of Astragaloside IV
15 grams of Astragalus = 24mg of Astragaloside IV
30 grams of Astragalus = 48mg of Astragaloside IV
60 grams of Astragalus = 96mg of Astragaloside IV
120 grams of Astragalus = 192mg of Astragaloside IV

I just wanted to make sure you guys are taking enough Astragalus to make a difference.

Cheers
A

Anthony is a vendor of Astragaloside IV. I believe he knows what he is talking about. This information does not help him sell his product so I give him an authoritative rating of 9 out of 10 on this one.

James Green also supports taking raw Astragalus powder and says it can be taken alone to lengthen telomeres.

* Note that I take 45g a day not 45mg. That was a typo.

When you start taking larger doses of Astragalus you might want to do regularly checkups on the iron levels in your blood. Unless you're a female in fertile age you might be running a risk of iron overload.

[solarfingers]

When you start taking larger doses of Astragalus you might want to do regularly checkups on the iron levels in your blood. Unless you're a female in fertile age you might be running a risk of iron overload.

I was taking 45mg of Astragalus powder a day. I felt very drained on it and I haven't taken it for weeks now...

[Turnbuckle]

The RDA for iron is 8 mg/day for adult men (and higher for some ages). According to Revegenetics--

Because a single pound of astragalus contains close to 647mg of Iron which can cause Iron poisoning, we do not suggest raw astragalus.

So 1.4 mg iron per gram. I'm presently taking 500 mg of a 4:1 extract, which would have at most 2.8 mg iron if fully concentrated by the extraction process (unlikely). Seems nothing to worry about. But it would be a worry for a 90:1 extraction, which is why Anthony mentions it, most likely.

[marcobjj]

The Maria Blasco study is the only in vivo study I know of. It dealt with TA65 specifically, used mice, not humans, did show a telomere length increase, no increased incidence of cancer, improved health throughout life... but no increase in longevity.

The telomerase activator TA-65 elongates short telomeres and increases health span of adult old mice without increasing cancer incidence

TA-65 intake does not impact on mean or maximum longevity of female mice
Analysis of the Kaplan–Meier survival curves of control vs. TA-65-treated female mice demonstrated no significant effects of TA-65 intake on survival (Fig. 6A,B). Accordingly, TA-65 administration for 4 months did not change statistically the mean or maximal lifespan of female mice under our experimental conditions

I think this is the strongest study for cycloastragenol but unfortunately mice seem to already have long telomeres and didn't show improved longevity. So Greenpower's longer term N=1 may be a better indicator with regard to humans. But you are absolutely right about N=1 being less than optimal. We need more. The Blasco study just isn't strong evidence to the contrary with regard to humans. And we don't know how Astragalus extract or even water would have fared as a control because she only compared TA65 to DMSO.

But... Mice have enormously long telomeres, and express telomerase all over the place, so wouldn't this be irrelevant? Maria Blasco is pretty good, or so I thought, so this is a puzzlement. I think Greenpower might have been misled by looking at average lengths rather than percentages of critically short telomeres. My understanding is that telomerase does not efficiently lengthen telomeres unless they are shorter than a particular critical length.

Personally I think that the results with "percentages of critically short telomeres" sounds more like a new hypothesis they made up from available data when all results showed that their test objective to prove they could lengthen the test subjects average telomere lengths failed. Like hav I'm also a bit sceptical to this paper because they don't seem to show the results for all the individual test subjects.

In a week or so I will have the time to present the data from my personal n=1 test from the beginning of the year (St. Astragalus/Gingko and Resveratrol periods), but they weren't that revolutionary. Might be that stress/cortisol must be avoided to get good test results. I therefore don't expect too much of the tests I will do now on Monday for my current half year regimen (St. Astragalus/Gingko and Resveratrol only when training) either. It will most likely serve best as a new "baseline" for the next test run.

However, I've got a somewhat unique opportunity to remove about all stress/cortisol for the next half year. I therefore think the next test period will be more interesting. I'm just thinking about what to include in the regimen.

I see that Anthony just added a new Astragalus based product called AT-90 to his product range. It would seem to be a 200mg ordinary Astragalus extract but with 90:1 purity (whatever this actually mean) which they have micronized to the average size of 1-3 microns. Any thoughts on this product?

The cell doesn't become senescent until it reaches a critically short number of telomeres (<4kb). In other words, from what is known so far a cell with 6kb is every bit as efficient as a cell 10kb pairs, so it's the percentage of short telomere that matters.

[GreenPower]

The cell doesn't become senescent until it reaches a critically short number of telomeres (<4kb). In other words, from what is known so far a cell with 6kb is every bit as efficient as a cell 10kb pairs, so it's the percentage of short telomere that matters.

But using data available from the report, is it actually possible to draw the conclusion that critically short telomeres were really extended? As far as I remember they only provided relative percentage numbers and not absolute numbers. You will likely get the same results if the cells with short telomeres quickly died off due to the cells reaching old age prematurely. In the long term this is probably not a desirable result.

Example:
The cells related to the immune system finds a new substance in the bloodstream which they deem poisonous. They will then try to fight this new substance, replicating fiercely in the process. The cells with critically short telomeres will die off and the surviving cells with longer telomeres will get a shorter average telomere length due to the their replication.

Because the number of cells with critically short telomeres (<4kb) are now much lower (most died) and the number of cells which still do not have critically short telomeres (>4kb) are still more numerous, the relative numbers might seem positive - although the absolute numbers probably wouldn't.

The report do tell us that the average length of the telomeres of the test subjects decreased in size, which makes me hesitant to rule out the second reason.

[marcobjj]

critically short telomere cells probably wouldn't participate in this fight though, once a cell becomes senescent it's essentially retired.but yeah it is possible that other processes could skew the percentages.

[hav]

If telomerase activation occurs only during cell division, no telomerase activator is going to actually affect any particular cell by making its telomeres longer. The most favorable outcome would be for the 2 cells that result from cell division to end up with longer telomeres than their parent. If that happened throughout an organism, I'd expect both the average telomere length to increase and the percent of telomeres with the shortest lengths to decrease. I'd expect the same result from a selective toxin that only targets cells with shorter telomeres. Logic suggests to me that the only value in focusing on the percent of cells with shorter telomeres is because that measure would probably show a larger magnitude of short term change.

I haven't seen any study showing that cells with critically short telomeres go into retirement or become inactive. I assume, however, that when they go into apoptosis and self-destruct that their remnants become toxic if not removed in a timely manner, and that if that starts happening at a high enough rate that it might impact a localized organ or tumor or, if it occurs everywhere throughout the organism, that death will follow. I saw one recent paper that speculated that senescence might trigger an inflammation response, but I think that accumulating dead cell parts are more likely to do that.

Howard

[marcobjj]

If telomerase activation occurs only during cell division, no telomerase activator is going to actually affect any particular cell by making its telomeres longer.

I haven't seen any study showing that cells with critically short telomeres go into retirement or become inactive

you need to look harder. there are many studies that support that both things occur. For instance:

http://www.nytimes.c...gests.html?_r=0


http://www.ncbi.nlm....pubmed/10757076


"Senescent cells differ from their presenescent counterparts in three way: 1) they arrest growth and cannot be stimulated to reenter the cell cycle by physiological mitogens; 2) they become resistant to apoptotic cell death; 3) they acquire altered differentiated functions. Replicative senescence occurs because, owing to the biochemistry of DNA replication, cells acquire one or more critically short telomere. The mechanism by which a short telomere induces the senescent phenotype is unknown. Recent findings suggest that certain types of DNA damage and inappropriate mitogenic signals can also cause cells to adopt a senescent phenotype. Thus, cells respond to a number of potentially oncogenic stimuli by adopting a senescent phenotype."

Edited by marcobjj, 19 August 2013 - 04:51 PM.

[hav]

If telomerase activation occurs only during cell division, no telomerase activator is going to actually affect any particular cell by making its telomeres longer.

I haven't seen any study showing that cells with critically short telomeres go into retirement or become inactive

you need to look harder. there are many studies that support that both things occur. For instance:

http://www.nytimes.c...gests.html?_r=0

http://www.ncbi.nlm....pubmed/10757076

Neither the Times article, the study its about, or the other article say or cite any study saying senescent cells become inactive. I've seen the abstract of that mouse study mentioned in the Times article and its interesting that getting rid of senescent cells improved long term health. But the abstract suggests the study didn't determine why. It speculates that senescent cells may secrete something detrimental. But I don't have access to the full-text so I don't know how good the basis that speculation might have or if they have a basis to eliminate the accumulation of decaying dead cells as an alternate explanation.

The mention of "long-term" in the abstract, btw, suggests that the drug they used may have acted over a long enough period to avoid too many cells being killed off at any one time. Be nice to know if the late-life clearance they administered was before or after mice showed any detrimental effects of aging... if it was the after, I think that would support their senescent cell secretion theory.

Howard

Edited by hav, 19 August 2013 - 05:58 PM.

[bsm]

Neither the Times article, the study its about, or the other article say or cite any study saying senescent cells become inactive. I've seen the abstract of that mouse study mentioned in the Times article and its interesting that getting rid of senescent cells improved long term health. But the abstract suggests the study didn't determine why. It speculates that senescent cells may secrete something detrimental. But I don't have access to the full-text so I don't know how good the basis that speculation might have or if they have a basis to eliminate the accumulation of decaying dead cells as an alternate explanation.

The mention of "long-term" in the abstract, btw, suggests that the drug they used may have acted over a long enough period to avoid too many cells being killed off at any one time. Be nice to know if the late-life clearance they administered was before or after mice showed any detrimental effects of aging... if it was the after, I think that would support their senescent cell secretion theory.

Howard

What senescent cells secrete is not a theory and not elusive. I suppose the long term secretion is the theory part but not the short term. But anyone can make the connection from short term effects of secretion to a lifetime of those secretions.

[GreenPower]

Today I ended my last test period and went through my ordinary medical tests. This mean I will start a new "half year test run" in a week or so. I've still not decided which of these regimens I will try.
a) 2 x AT-90 + Training + Meditation + LCHF,
b) 2 x Standardized Astragalus (Solgar) + 2 x AT-90 + Training + Meditation + LCHF,
c) 4 x Standardized Astragalus (Solgar) + Training + Meditation + LCHF (similar to now, but excluding Gingko Biloba and doubling the dose of Astragalus), or
d) using up my old/expired Cycloastragenol/Chitosan with a dose like 2 x 10mg Cyclo + Training + Meditation + LCHF. Or perhaps 2 x 15 mg or 2 x 20 mg (expired) Cyclo if I can manage the dose. The Cyclo expired like a year ago, but when asking the support at Revgenetics I understood it should be possible to compensate for this by increasing the dosage.

I plan to take Resveratrol whenever I train and then skip the other stuff during half a day. I'll probably have a resting phase during some weeks in the middle of the test run. For this test run I've removed all stressful environmental factors which might (or might not) have had a negative impact on earlier test runs.

Do you have suggestions and arguments on which of the regimens should be the most interesting to test?

Edited by GreenPower, 19 August 2013 - 08:55 PM.

[hav]

What senescent cells secrete is not a theory and not elusive. I suppose the long term secretion is the theory part but not the short term. But anyone can make the connection from short term effects of secretion to a lifetime of those secretions.

Here's the full-text of a fairly recent study on the subject. Their characterization of secretions from normal senescent cells starts out sounding uncertain with a change in tune further on:

Mitochondrial DNA damage induces apoptosis in senescent cells

. The senescence response might drive aging by depleting progenitor cell pools. Additionally, the ability of senescent cells to secrete inflammatory molecules might contribute to tissue repair, but persistent senescent cells might drive chronic inflammation, a major risk factor for age-related pathologies
...
One striking characteristic of senescent cells is the secretion of inflammatory cytokines, proteases and other molecules that can alter the tissue microenvironment.^{18, 33, 45, 46, 47} We and others have shown that these secreted factors can disrupt normal tissue structure and function, induce malignant phenotypes in pre-malignant and non-aggressive cells and stimulate malignant tumorigenesis in vivo through inflammation and vascularization.^{13, 14, 18, 45, 46, 48}

The 2nd part about inflammatory cytokines and proteases sounds more definite until you look at the cites which all have to do with either cancer or tumor cells or cells subjected to DNA damage, usually with sub-lethal radiation exposure, to induce either senescence or cancer. The title itself is kind of a give away since by definition, a senescent cell doesn't need anything more to induce apoptosis. What they really proved is that DNA damage can lead to cancer.

Which , btw, is the same logical defect revealed in #2 below:

"Senescent cells differ from their presenescent counterparts in three way: 1) they arrest growth and cannot be stimulated to reenter the cell cycle by physiological mitogens; 2) they become resistant to apoptotic cell death; 3) they acquire altered differentiated functions.

... which is actually what distinguishes a cancer cell from an normal senescent cell.

Howard

[hav]

Today I ended my last test period and went through my ordinary medical tests. This mean I will start a new "half year test run" in a week or so. I've still not decided which of these regimens I will try.
a) 2 x AT-90 + Training + Meditation + LCHF,
b) 2 x Standardized Astragalus (Solgar) + 2 x AT-90 + Training + Meditation + LCHF,
c) 4 x Standardized Astragalus (Solgar) + Training + Meditation + LCHF (similar to now, but excluding Gingko Biloba and doubling the dose of Astragalus), or
d) using up my old/expired Cycloastragenol/Chitosan with a dose like 2 x 10mg Cyclo + Training + Meditation + LCHF. Or perhaps 2 x 15 mg or 2 x 20 mg (expired) Cyclo if I can manage the dose. The Cyclo expired like a year ago, but when asking the support at Revgenetics I understood it should be possible to compensate for this by increasing the dosage.

I plan to take Resveratrol whenever I train and then skip the other stuff during half a day. I'll probably have a resting phase during some weeks in the middle of the test run. For this test run I've removed all stressful environmental factors which might (or might not) have had a negative impact on earlier test runs.

Do you have suggestions and arguments on which of the regimens should be the most interesting to test?

Your "c" option sounds like what I'm doing myself. I take 2 caps of standardized astragalus extract (Now brand) 2x daily. But I cycle it every other week with c60/oo and resveratrol on the off weeks. But I think you'd be good as long as you separate the HF ingestion from the astragalus and separate any chitosan ingestion from the HF and/or resveratrol. The AT90 sounds interesting but if I had cycloastragenol on hand I'd use that up first. Assuming its still good.

Howard

Edited by hav, 19 August 2013 - 10:03 PM.