Astragalus, Astragaloside IV

This is an interesting study, however it does not show if folks with longer telomeres lived longer.

It simply states that 1/3 of the folks in the study had stable or grew the telomeres during a 10 year period. I find this fantastic, as it certainly allows for an outside influence that can activate the hypothetical cellular TL regulating mechanism, that these folks are proposing.

If these individuals don't live longer and seem morphologically younger, that would undermine the basis for thinking that increasing telomere length in humans would be anti-aging.

That is true, but this study does not provide this data. It also does not show how quickly the telomere length shortened after this increase in length, until the death of a subject. It doesn't provide pictures of the subjects, etc. Now, what is interesting is that If it's true that telomerase focuses on short telomeres over longer telomeres as suggested by the study, it's certainly possible that telomerase may have not worked very much or at all after a certain length was achieved... so...

According to part of the study:

The individual telomere attrition rate was inversely correlated with initial TL at a highly significant level (r = –0.752, P<0.001), indicating that the attrition rate was most pronounced in individuals with long telomeres at baseline.

It would seem that at one point when achieving, or having long telomeres, the attrition rate would be very much increased. We don't have the data for attrition after the later part of the 10 year period, so we don't know if there was rapid attrition after this period of telomere lengthening. I figure activating telomerase, say by activating it through a capsule, may limit the speed of attrition of the longer telomeres.

Now, if you want evidence that telomere is not associated with age at all, this study simply doesn't provide that kind of evidence. What it seems to provide, is a hypothetical TL regulating mechanism, that I find interesting. The other thing is that this study is strictly on blood cells, while other cells were not tested.


What I really found interesting was the talk about Cancer:

The working hypothesis that blood cell TL can indicate a later development of a malignant tumor was not supported in the present study. This hypothesis emanates from data showing altered TL in cases with a variety of malignancies. In urinary bladder, head and neck, lung, and renal cell cancers, shortened blood telomeres have been described at diagnosis, whereas data on breast cancer indicate unchanged or longer telomeres compared to controls [12]–[15]. Since no difference in TL existed between cases and controls, neither ≥9 (sample 1) nor 0–11 (sample 2) years before the appearance of a malignancy, we conclude that blood TL is not a prediagnostic biomarker for malignancy per se.

Cheers
A

Edited by Anthony_Loera, 13 May 2009 - 10:21 PM.

FYI Folks,

The new formulation will have 100mg of Astragaloside IV per capsule, and Chitosan.

For folks taking regular Astragalus extract daily, you will need to take 62.5 grams a day to achieve the same amount.

Cheers.
A

Will the old dosage of 33mg without chitosan still be available? I would prefer to stay on the same 3x33mg/day dosage until I've completed at least one more 3-month period.

GreenPower,
we have discontinued the 33mg altogether (sorry).
We only have 100mg with Chitosan that is currently shipping to everyone that has been waiting for it.

Cheers

A

Good for them, but not for me. In order to complete my second three-month-period with approximately the same dose, I will then have to buy capsules of 40mg from the other company that sells them - and combine them with ordinary Astragalus to make them as similar as possible to what I've been using during my first three-month-period.

If I don't get a positive result on my next FlowFISH-test I might consider the chitosan version, though.

FYI Folks,

The new formulation will have 100mg of Astragaloside IV per capsule, and Chitosan.

For folks taking regular Astragalus extract daily, you will need to take 62.5 grams a day to achieve the same amount.

Cheers.
A

Will the old dosage of 33mg without chitosan still be available? I would prefer to stay on the same 3x33mg/day dosage until I've completed at least one more 3-month period.

GreenPower,
we have discontinued the 33mg altogether (sorry).
We only have 100mg with Chitosan that is currently shipping to everyone that has been waiting for it.

Cheers

A

Good for them, but not for me. In order to complete my second three-month-period with approximately the same dose, I will then have to buy capsules of 40mg from the other company that sells them - and combine them with ordinary Astragalus to make them as similar as possible to what I've been using during my first three-month-period.

If I don't get a positive result on my next FlowFISH-test I might consider the chitosan version, though.

...but when looking through what ingredients they have used, I see one called "sodium lauryl sulfate", which according to wikipedia (http://en.wikipedia....laureth_sulfate) is a well known carcinogen, which may cause permanent baldness is used in a shampoo. Not exactly what I would like to eat. I will have to think about this for a while, I think.

Sorry I have made it difficult with the new Astral Fruit.
I didn't know the other company used any carcinogens (Now, that was a surprise to me...).

Well... try this:
Take 1 of our new capsules, open and place powder into a bowl, split it into 3 parts, then mix with a thick liquid that masks the flavor for each part...

The problem is masking the flavor/smell of the stuff.

A

Edited by Anthony_Loera, 15 May 2009 - 08:06 PM.

Here's the COA for the Astragalus material, for those wondering about safety and purity.

Cheers
A

It seems that the jury is still very much out. So much back and forth as to whether taking a tolemerase activator (specifically astragaloside or even whatever "TA-65" actually is) will promote cancer vs. promote longevity via extending cellular life. The truth is that although I'm VERY interested in "cellular imortality" there is still not enough evidence that is generally, nor widely, accepted that astra. is both safe and effective. Personally I do believe that it can promote cellular longevity (under the perfect circumstances and with the perfect doses and regime). However "hacking" my telemeres without irrefutable and widely accepted protocals, using substances I have little to no -unbiased- evidence regarding purity or efficacy, while risking cancer or any other life shortening/damaging effects? I think I'll stick with resveratrol. After all, I think the path to immortality, at least for me, will be "first, do no harm"...

Just my two cents worth.

After spending time going through 10-20 different studies/presentations on Telomeres and Telomerase, I also came to nearly the identical conclusion. There are too many unknowns.

There are too many unknowns.

Has it at least been tested on normal mice survival?

Edited by AgeVivo, 16 May 2009 - 08:58 AM.

It seems that the jury is still very much out. So much back and forth as to whether taking a tolemerase activator (specifically astragaloside or even whatever "TA-65" actually is) will promote cancer vs. promote longevity via extending cellular life. The truth is that although I'm VERY interested in "cellular imortality" there is still not enough evidence that is generally, nor widely, accepted that astra. is both safe and effective. Personally I do believe that it can promote cellular longevity (under the perfect circumstances and with the perfect doses and regime). However "hacking" my telemeres without irrefutable and widely accepted protocals, using substances I have little to no -unbiased- evidence regarding purity or efficacy, while risking cancer or any other life shortening/damaging effects? I think I'll stick with resveratrol. After all, I think the path to immortality, at least for me, will be "first, do no harm"...

Just my two cents worth.

After spending time going through 10-20 different studies/presentations on Telomeres and Telomerase, I also came to nearly the identical conclusion. There are too many unknowns.

I respect your conclusion prophets, but I simply don't agree with you.
Probably because of what I know, from a specialist in the field, doing work about it in the present, (and not from a presentation or study).

Cheers
A

Edited by Anthony_Loera, 17 May 2009 - 01:54 PM.

There are too many unknowns.

Has it at least been tested on normal mice survival?

that would be a minimal thing to know, right?
well, anyone, just ask the question in this thread, we'll look for the answer

There are too many unknowns.

Has it at least been tested on normal mice survival?

that would be a minimal thing to know, right?

It might be the minimal thing in that you would choose not to take a supplement until it's been tested in mice, and that the FDA would not allow a safety trial in humans without pre-clinical proof in mice that something works. But it's not a minimal thing to know as in the first step that researchers would take. Often they start with in vitro studies (as with TA-65, I believe, to see if it activates telomerase in human cells in a petri dish) and/or in lower animals (e.g. resveratrol was tested on yeast, then worms, then fish, before testing on mice).

But it's perfectly reasonable for someone to hold out for testing on mice, or even large-scale human studies. (Although for longevity studies in humans, many of us don't want to wait for the study that gives a supplement or drug to 20-year-olds and reports on when they die of old age compared to the control group, so I can see why you might choose mice as your minimum.)

You took my question a step further. I meant that before considering taking telomere-extending compounds, since there are clearly potential cancer risks,

• the first step is to avoid ignorance about already known effects on survival in normal mice. Perhaps are there already such results with astragalus? with TA-65?
• some further steps, that you describe, are to wait or not for additional safety knowledge, in particular depending on one's attitude towards risk, but those are further steps.

Here is a thread to ask for (and answer if you can) known effects on survival.

Edited by AgeVivo, 21 May 2009 - 08:11 AM.

Hi AgeVivo,

Telomerase is not an Oncogene, it does not cause cancer.
I have repeatedly stated this many times. Other folks have stated this,

Geron has stated this everywhere:
Here: http://www.tascience...ta_oncogene.pdf
Geron's study: http://www.ncbi.nlm....pubmed/11850774
Telomerase does not cause cancer: http://www.geron.com...telomerase.aspx

Telomerase provides no cancer risk.

A

I've been following the Astragalus compounds for a while now and I'm very confident that telomerase activation is a keeper. I'm not so sold on telo inhibitors though, to me it seams as though they just reduce the stress of the chomosome using telomere length and while this may prevent certain deadly diseases associated with this stress by letting someone live longer as they are not prone to being killed by the diease resulting from stress of the chromosome. In the long term I think it's much more benefitial to have longer telos and to work towards identifying and eliminating the cause of stress to the chromosome.

Also from reading this thread it sounds as if our bone marrow stem cells have their limits and won't be able to sustain us forever. So I would think that reducing the demand on our stem cells using a TA would be better for the long run as our bodies have other built in ways to deal with damaged and potentially damaged cells, esp if one starts using a TA when they are young to pre-empt the degradation of the systems that protect us from our damaged cells.

Anyways, my main reason for posting is because I was wondering if a. IV or cycloastraganol proteins could be replicated by our cells. It would be interesting to dope the stem cells of some mice with it and see if we can be our own source of the stuff.

Edited by theimoguy, 21 May 2009 - 09:54 PM.

Learn and read more before you come to conclusions or post.

Neither astrogaloside IV nor cycloastraganol are proteins.

I've been following the Astragalus compounds for a while now and I'm very confident that telomerase activation is a keeper. I'm not so sold on telo inhibitors though, to me it seams as though they just reduce the stress of the chomosome using telomere length and while this may prevent certain deadly diseases associated with this stress by letting someone live longer as they are not prone to being killed by the diease resulting from stress of the chromosome. In the long term I think it's much more benefitial to have longer telos and to work towards identifying and eliminating the cause of stress to the chromosome.

Also from reading this thread it sounds as if our bone marrow stem cells have their limits and won't be able to sustain us forever. So I would think that reducing the demand on our stem cells using a TA would be better for the long run as our bodies have other built in ways to deal with damaged and potentially damaged cells, esp if one starts using a TA when they are young to pre-empt the degradation of the systems that protect us from our damaged cells.

Anyways, my main reason for posting is because I was wondering if a. IV or cycloastraganol proteins could be replicated by our cells. It would be interesting to dope the stem cells of some mice with it and see if we can be our own source of the stuff.

Another interesting study:

Multivitamin use and telomere length in women1,2,3
Qun Xu, Christine G Parks, Lisa A DeRoo, Richard M Cawthon, Dale P Sandler and Honglei Chen

1 From the Epidemiology Branch, National Institute for Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC (QX, CGP, LAD, DPS, and HC), and the Department of Human Genetics, University of Utah, Salt Lake City, UT (RMC).

2 Supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (Z01ES044005 AND Z01ES101986), and the Department of Defense Breast Cancer Research Concept Award (BC045286).

3 Address reprint requests and correspondence to H Chen, Epidemiology Branch, National Institute of Environmental Health Sciences, 111 TW Alexander Drive, PO Box 12233, Mail drop A3-05, Research Triangle Park, NC 27709. E-mail chenh2@niehs.nih.gov.

ABSTRACT

Background: Telomere length may be a marker of biological aging. Multivitamin supplements represent a major source of micronutrients, which may affect telomere length by modulating oxidative stress and chronic inflammation.

Objective: The objective was to examine whether multivitamin use is associated with longer telomeres in women.

Design: Cross-sectional analysis of data from 586 early participants (age 35–74 y) in the Sister Study. Multivitamin use and nutrient intakes were assessed with a 146-item food-frequency questionnaire, and relative telomere length of leukocyte DNA was measured by quantitative polymerase chain reaction.

Results: After age and other potential confounders were adjusted for, multivitamin use was associated with longer telomeres. Compared with nonusers, the relative telomere length of leukocyte DNA was on average 5.1% longer among daily multivitamin users (P for trend = 0.002). In the analysis of micronutrients, higher intakes of vitamins C and E from foods were each associated with longer telomeres, even after adjustment for multivitamin use. Furthermore, intakes of both nutrients were associated with telomere length among women who did not take multivitamins.

Conclusion: This study provides the first epidemiologic evidence that multivitamin use is associated with longer telomere length among women.

Received for publication September 18, 2008. Accepted for publication February 8, 2009.

http://www.ajcn.org/...cn.2008.26986v1

Edited by smithx, 26 May 2009 - 08:31 AM.

Nice find SmithX!!

thanks
A

Anthony,

Are you doing any sort of discount for paid up imminst members like you did for resv?

Anthony, are you still taking your astral fruit product 3 or 4 hours after you take resveratrol? Are you finding that this is working? I know there are others that believe resveratrol and astralagus should be rotated on a 2 week on 2 week off schedule. The reason I ask is because I take resveratrol and I am thinking of adding astragaloside IV to my regimen.

Hi Resvhead,

let me ask you this, we can probably do a discount for members, however we will eventually have 2 Astral Fruit products (at least that is my aim). The next one, will have a higher price (same amount of capsules). Would you like a member discount on the current Astral Fruit, or our second generation product?

Morganator... I am taking Astral Fruit 1 week, and micronized resveratrol the following week. (1 week on / 1week off) To completely rule out resveratrol inhibition for my next tests. It is possible that resveratrol may have inhibited Astral Fruit intake, and I need to rule it out.

If it makes a difference in my own tests, I will definitely suggest the same procedure to others.

thanks
A

Edited by Anthony_Loera, 27 May 2009 - 04:03 PM.

Hi Resvhead,

let me ask you this, we can probably do a discount for members, however we will eventually have 2 Astral Fruit products (at least that is my aim). The next one, will have a higher price (same amount of capsules). Would you like a member discount on the current Astral Fruit, or our second generation product?

Hi Anthony,

I didn't realise that you were planning on bringing out another Astral Fruit product. Given a higher price for the same amount f capsules, I can only assume that they will be greater potency (quantity) or absorbancy or purity? Perhaps a cycloastraganol product?

Personally, I am not sure that I could afford significantly more for this product, but that would ultimately depend on what is being offered.

If you are looking at $60 or $70 for (1 month of) the new product, then I personally would like the discount to be on this new product. If you are talking $90 to $100 for (1 month of) the new product, then I personally would like the discount to be on the existing product. What do others here think?

Remember, I need to keep some money aside for MasterGene P16 when it arrives, which is when....?

Anthony, I do like the way you try to innovate and explore new options. It is a shame that really fluffy Resveratrol worked out too expensive - did you use the test batch yourself?

Hi Resvhead,

I understand the issue with pricing. So we are still going over this to help provide members a discount. When we start the discount for P98 / P99 we figured that folks on this board wanted the base material they can use, play with, dissolve in alcohol, etc. Astral Fruit is a little different.

Regarding MasterGene P16:
It has taken us nearly 6 months to get really close to providing Astral Fruit using our extracted <material> from astragalus, so I believe it may take about the same for Mastergene P16. Nano-res powder can still be made, I still have the Jar of it here in the office... but it seems like the best bang for the buck for most folks may continue to be micronized trans-resveratrol for now, as the nano-powder will sound a bit expensive for many.

Anyway, back to Astragalus and Astragaloside IV...
For Astral Fruit, the discount will be aimed to help bring in new folks to imminst.org as well as for current members. This decision really stemmed from the fact that we can't support fightaging.org, mprize.org, longevitymeme.org or the new website http://www.mfoundation.org/ like we once were able to. So, now we will help support this website through discounts for members, and I am leaning to open this up to more products in the near future.

Still chewing on this, but my mind is changing and as I type this, and I may just include discounts for both Astral Fruit products, and maybe a couple of others...

Cheers
A

Edited by Anthony_Loera, 28 May 2009 - 03:10 PM.

Hi Anthony,
I have two questions:

1) Imagine a scenario where a person taking a telomerase activating supplement already has a rapidly dividing but telomerase negative tumor in their body. Normally these cells would hit the hayflick limit and senesce, but with a telomerase activator to extend their telomeres and replicative potential, the tumor cells would have more time to aquire more mutations, one of which could make them telomerase positive (or ALT positive), letting it transform into a malignant cancer.

Can you explain why this scenario isn't something to worry about?

2) To everyone who's taking (or considering taking) telomerase activating supplements - what diseases of old age do you think this is going to help prevent (or postpone) and how? It's not obvious (to me, at least) how this will help with heart attacks, alzheimer's, cancer (possibly quite the opposite) etc, that most people actually die of.

Hi AgeVivo,

Telomerase is not an Oncogene, it does not cause cancer.
I have repeatedly stated this many times. Other folks have stated this,

Geron has stated this everywhere:
Here: http://www.tascience...ta_oncogene.pdf
Geron's study: http://www.ncbi.nlm....pubmed/11850774
Telomerase does not cause cancer: http://www.geron.com...telomerase.aspx

Telomerase provides no cancer risk.

A

Hi marainein,

I believe this post may explain things for question number 1:
http://www.imminst.o...mp;#entry308551


For question number 2:
Read this post on this same thread regarding heart if you are an old rat, and only taking astragaloside iv without considering telomerase:
http://www.imminst.o...o...st&p=320093

Others of course are possible with telomerase, see the UCLA Effros studies for more. Here is one...
http://www.redorbit...._aging_process/

As an aside, I would think folks would combine things to maintain health, and not rely solely on one item or mechanism to maintain health.

Cheers
A

Edited by Anthony_Loera, 31 May 2009 - 09:04 PM.

Hi AgeVivo,

Telomerase is not an Oncogene, it does not cause cancer.
I have repeatedly stated this many times. Other folks have stated this,

Geron has stated this everywhere:
Here: http://www.tascience...ta_oncogene.pdf
Geron's study: http://www.ncbi.nlm....pubmed/11850774
Telomerase does not cause cancer: http://www.geron.com...telomerase.aspx

Telomerase provides no cancer risk.

A

Hi Anthony,

Like you i would have liked that there is no cancer risk but i'm afraid there is.
I showed your message and asked jgpeyer about cancer risk of telomerase-stimulation.

The answer looks quite right to me:
- regarding the strict oncogene definition telomerase is not an oncogene
- regarding cancer risk telomerase does provide cancer risk

Summary: Telomerase is not an Oncogene in the classical definition of an oncogene because it is not a causative agent of cancer. However, assertions like "telomerase [expression] provides no cancer risk" are false. (...) A large number of aspiring tumors spontaneously regress because they reach the Hayflick limit and fail to mutate further (one well-characterized example is Stage IVS Neuroblastoma, which occurs in infants). To give aspiring tumors a free pass around an evolutionary barrier could result in a very profound increase in late-stage cancer incidence (possibly multiple orders of magnitude). full answer ...

Also, I remember that Maria Blasco's team had to use "very-cancer-resistant" mutant mice to get probable life extension via telomerase overexpression. This makes me think that in "more normal" mice they rather observed accelerated death. Here is a thread to ask for (and answer if you can) known effects [of telomerase stimulation, typically] on survival.

Edited by AgeVivo, 05 June 2009 - 09:19 AM.

Hi AgeVivo,

the following is my reply to jgpeyer since I am a pretty flexible guy:
============================================

Hi James,

I am the person that stated the following:

Hi AgeVivo,

Telomerase is not an Oncogene, it does not cause cancer.
I have repeatedly stated this many times. Other folks have stated this,

Geron has stated this everywhere:
Here: http://www.tascience...ta_oncogene.pdf
Geron's study: http://www.ncbi.nlm....pubmed/11850774
Telomerase does not cause cancer: http://www.geron.com...telomerase.aspx

Telomerase provides no cancer risk.

A

I am no scientist, however this is my understanding:

1- I suppose I need to understand that giving "aspiring tumours" a free pass buy inducing telomerase for brief amounts of time is just an opinion, and it has not been proven. If so, I would like to be educated on this by pointing me to studies.

2- I believe that telomerase activating supplements (as well as some diets) transiently turn on the hTERT gene to extend the number of times the cell can replicate and to give it a younger phenotype.

Since this is done normally throughout life, I do not believe it provides a greater cancer risk. Specially when folks have the ability to stop this simply by stopping the intake of a telomerase activator / diet. So, I need to make a change in my statements since I am not married to them. I will state that my statement should now be as follows:

"Transient telomerase provides no increased cancer risk."

I have also talked to Steve Coles from the GRG where he states that clinical data from AIDS patients at UCLA is available that discredits the notion that telomere elongation will increase the risk of cancer.

==========================================================

Now regarding your quote...

This makes me think that in "more normal" mice they rather observed accelerated death.

link to the study, and let me know what page these folks observed an accelerated death. If you cannot provide this information, you are simply making things up.

Actually a link to a study here would be appropriate when you reply, regardless of the point you are trying to make. Here I found it for you.... http://pubmed.org/19013273 and I don't think the "more normal" mouse presumption was tested in there. (ok, I haven't looked, but the study is not about activating cancer in mice using telomerase, it's about delaying aging using telomerase.)


thanks
A

Edited by Anthony_Loera, 05 June 2009 - 02:34 PM.

The Bianco study says

To circumvent this problem (ie. make cancer resistanct mice), we have constitutively expressed telomerase reverse transcriptase (TERT), one of the components of telomerase, in mice engineered to be cancer resistant by means of enhanced expression of the tumor suppressors p53, p16, and p19ARF.

Ok... now quick question:
What dietary supplements have shown to up-regulate or enhance gene expression for these?

P53 - Resveratrol (we know where to get that already)
P16 - Saikosaponin A (ridiculously expensive stuff, trust me but that is a new product of ours)
P19ARF - Unknown

...
So, if telomerase does not increase your current cancer risk, finding ways (or supplements) to enhance P53, P16, and P19ARF may actually help decrease the risk. And if you are a mouse and increase telomerase activity... this may delay aging by 50% according to the fightagaing link in your post AgeVivo? http://www.fightagin...-telomerase.php

However, most folks who don't care for telomerase, like yourself AgeVivo, may consider taking resveratrol and saikosaponin a (not b, or c, or d...) to help support a decrease in cancer risk.

Well that's what we are working on as well. We aren't settling for Astral Fruit, and Resveratrol... we have another item on our website that is not available yet, but that many have asked me about as well. Now, If only we can find a supplement for P19ARF....



Cheers
A

Edited by Anthony_Loera, 05 June 2009 - 02:50 PM.

He he, the potentials seems quite important, don't they? It ranges between telomerase-activation-based supplements providing non-benign cancers and longer lives...

My provoking guess (This makes me think that in "more normal" mice they rather observed accelerated death) was a way to make you/us verify your assertion (Telomerase provides no cancer risk). It's nice that you started looking at the papers, i'll have a deep look too. Once more knowledgeable, perhaps we'll better know what to think or what to test.

Cheers.

Edited by AgeVivo, 05 June 2009 - 04:15 PM.

Hi AgeVivo,

No, the new statement came from reading James posts, not from your statement.

The old statement was: Telomerase provides no cancer risk.
It was simply too broad as it pertains to telomerase in all cells, including immortal cells.

My statement now becomes:
Transient telomerase provides no increased cancer risk.

It pertains to telomerase that can be turned on briefly, which is what dietary telomerase activators do and fits nicely with what Scoles from the GRG mentioed about UCLA findings, as well as the normal telomerase function that is activated and serves us throughout life.

A

Edited by Anthony_Loera, 05 June 2009 - 04:16 PM.

hmm... I need a deep reading of the UCLA paper to have my own estimate of whether the "no additional cancer risk" holds.
Once more knowledgeable, perhaps i'll better know what to think or what to test.

"The old statement was: Telomerase provides no cancer risk.
It was simply too broad as it pertains to telomerase in all cells, including immortal cells.

My statement now becomes:
Transient telomerase provides no increased cancer risk."

Perhaps I missed it; was there a study you pointed out showing transient telomerase / telomerase activators wouldn't speed the growth of an existing cancerous tumor, or cause cells on the threshold of turning cancerous to do so? I remain interested in Astragaloside IV, and Anthony I appreciate the candor of your posts in this thread, despite the fact you are at the same time attempting to promote the product.

I continue to remain a skeptic regarding A. IV's overall long-term benefits from a risk v. reward ratio. I look forward to the kind of studies we've seen with resveratrol that will change my mind.

(In the meantime, I will continue to purchase your micronized resveratrol (I purchased a massive bag of the power from you).