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Old human cells rejuvenated in breakthrough discovery on ageing

senescent cells rejuvenation

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#61 Oakman

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Posted 14 December 2017 - 04:30 PM

It does not appear that DIY approach can do what pharma companies do to make lipo formulations. This gives some of the methods used "Liposomal Formulations in Clinical Use: An Updated Review", January 2017. Of course, they are likely delivering toxic pharma drugs, not relatively safe compounds. Ok, so here, True Liposomes are hard to make correctly, I found a good description of how something similar can be done with common materials. Certainly not as difficult as phara products, but I would not be able to do this, with proper validation of product quality and size, in my kitchen, sad to say. Anyone else?



#62 greenwich

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Posted 14 December 2017 - 04:33 PM

@Nate-2004 Do you get caffeine jitters and maybe a headache after 4 espresso drinks like lattes or Americanos? It just occurred to me that the symptoms of caffeine intolerance are the same symptoms of having too many cups of coffee. Maybe by having too many cups of coffee... a person is temporarily exhausting the supply of CYP1A2?


Edited by greenwich, 14 December 2017 - 04:35 PM.


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#63 greenwich

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Posted 14 December 2017 - 05:54 PM

A 2016 study showed free (undigested) resveratrol in the bloodstream of subjects who took a single 500mg trans-resveratrol tablet. 75ng/mL @ 30 minutes, 10ng/mL @ 7 hours.
 
Interesting chart. It also shows the time-curve of the metabolites (glucuronated resveratrol, sulfated resveratrol).
 
 
 

Edited by greenwich, 14 December 2017 - 05:55 PM.

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#64 Nate-2004

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Posted 14 December 2017 - 07:07 PM

@Nate-2004 Do you get caffeine jitters and maybe a headache after 4 espresso drinks like lattes or Americanos? It just occurred to me that the symptoms of caffeine intolerance are the same symptoms of having too many cups of coffee. Maybe by having too many cups of coffee... a person is temporarily exhausting the supply of CYP1A2?

 

No I very rarely get the jitters though it does make my essential tremor worse to some mild degree. I've managed to curb that some with MCT oil and berberine I think, which is more effective when I'm on keto.



#65 Nate-2004

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Posted 14 December 2017 - 07:20 PM

 

A 2016 study showed free (undigested) resveratrol in the bloodstream of subjects who took a single 500mg trans-resveratrol tablet. 75ng/mL @ 30 minutes, 10ng/mL @ 7 hours.
 
Interesting chart. It also shows the time-curve of the metabolites (glucuronated resveratrol, sulfated resveratrol).
 
 
 

 

 

Which one on these charts is free trans resveratrol? Did they detect it at all or is this the "non digested"?


Edited by Nate-2004, 14 December 2017 - 07:22 PM.


#66 greenwich

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Posted 14 December 2017 - 07:39 PM

 

Which one on these charts is free trans resveratrol? Did they detect it at all or is this the "non digested"?

 

 

It's the "non-digested" trans-resveratrol (nd) shown on chart 1, which would be pure trans-resveratrol.



#67 Rocket

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Posted 14 December 2017 - 08:54 PM

Well Nate, something tells me if your protocol was working and rejuvenating a % of your cells that you would notice something. Perhaps sulfation isn't being overwhelmed by 600mg of R every couple of hours. CYP1A2 may very well be suppressed by what you are doing but if sulfation is still working, then it probably doesn't matter.

 

 



#68 HaplogroupW

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Posted 14 December 2017 - 09:08 PM

Well Nate, something tells me if your protocol was working and rejuvenating a % of your cells that you would notice something.

Doesn't skin have a turnover on the order of months, longer as we get older? I'd guess cells might have to do some dividing before you'd see any difference.


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#69 Rocket

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Posted 15 December 2017 - 01:34 AM

Well Nate, something tells me if your protocol was working and rejuvenating a % of your cells that you would notice something.

Doesn't skin have a turnover on the order of months, longer as we get older? I'd guess cells might have to do some dividing before you'd see any difference.

Turnover,yes, but rejuvenation would be very fast.

But Nate is doing oral R which would be the entire body and not just the top dermal layer of Nate.
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#70 sthira

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Posted 15 December 2017 - 01:50 AM

I thought R was generally considered a flub? I took it several years ago -- varying intensities and absorption modalities -- "noticed" nothing. I apologize for falling behind here -- is there some new resveratrol finding I'm missing? Why the renewed interest?

#71 Rocket

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Posted 15 December 2017 - 12:49 PM

I thought R was generally considered a flub? I took it several years ago -- varying intensities and absorption modalities -- "noticed" nothing. I apologize for falling behind here -- is there some new resveratrol finding I'm missing? Why the renewed interest?

 

That's what this thread is about! When R is added to cells without going through the gut / liver, cells are rejuvenated. Read the first few posts. R is a flub because it is metabolized by sulfation in the intestines (and I think CYP1A2 in the liver). We're trying to stop it from being metabolized into benign and useless metabolites.

 

Hence, the talk about use DMSO to bypass digestion and ways to beat CYP1A2 and sulfation.


Edited by Rocket, 15 December 2017 - 12:50 PM.

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#72 Nate-2004

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Posted 15 December 2017 - 04:22 PM

 

 

Well Nate, something tells me if your protocol was working and rejuvenating a % of your cells that you would notice something.

Doesn't skin have a turnover on the order of months, longer as we get older? I'd guess cells might have to do some dividing before you'd see any difference.

Turnover,yes, but rejuvenation would be very fast.

But Nate is doing oral R which would be the entire body and not just the top dermal layer of Nate.

 

 

@Rocket I'm taking it sublingually with the DMSO/Quercetin mix. I'm also applying it topically the same day in a similar mixture with NAM and urea minus the quercetin.


Edited by Nate-2004, 15 December 2017 - 04:22 PM.


#73 Nate-2004

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Posted 15 December 2017 - 04:24 PM

 

I thought R was generally considered a flub? I took it several years ago -- varying intensities and absorption modalities -- "noticed" nothing. I apologize for falling behind here -- is there some new resveratrol finding I'm missing? Why the renewed interest?

 

That's what this thread is about! When R is added to cells without going through the gut / liver, cells are rejuvenated. Read the first few posts. R is a flub because it is metabolized by sulfation in the intestines (and I think CYP1A2 in the liver). We're trying to stop it from being metabolized into benign and useless metabolites.

 

Hence, the talk about use DMSO to bypass digestion and ways to beat CYP1A2 and sulfation.

 

 

Exactly. The goal here is to try and resolve the bioavailability issues which is why I think it's been a flub, in vivo it's just metabolized too quickly and historically the dosing as a result has been far from effective. It could be that CYP1A2 and sulfation aren't our only targets. There's also the confounding effect from the bioavailability of quercetin, which may not be as good at preventing sulfation as would be ideal.


Edited by Nate-2004, 15 December 2017 - 04:25 PM.


#74 Rocket

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Posted 15 December 2017 - 05:29 PM

Nate, did you stop doing topical R+DMSO? Or were you ever doing that?



#75 greenwich

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Posted 15 December 2017 - 05:30 PM

Resveratrol has a real affinity for sulfur though, which is why there are at least two ways it can get sulfated in the gut. DMSO has a sulfur with two unbonded electrons... i'm no chemist but I think there's a possibility DMSO will sulfate it? 


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#76 Rocket

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Posted 15 December 2017 - 06:17 PM

Resveratrol has a real affinity for sulfur though, which is why there are at least two ways it can get sulfated in the gut. DMSO has a sulfur with two unbonded electrons... i'm no chemist but I think there's a possibility DMSO will sulfate it? 

 

Well, that's interesting!

 

Once again, need something you can inject subq. Skip the gut and the liver altogether.

 

Some bodybuilders were injecting R on the BB forums. God only knows what kind of concoction they were pinning themselves with.


Edited by Rocket, 15 December 2017 - 06:20 PM.


#77 Nate-2004

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Posted 15 December 2017 - 08:26 PM

Nate, did you stop doing topical R+DMSO? Or were you ever doing that?

 

Still doing it but only on that one day a week in which I'm doing the R thing. Maybe I should make it twice a week.


Resveratrol has a real affinity for sulfur though, which is why there are at least two ways it can get sulfated in the gut. DMSO has a sulfur with two unbonded electrons... i'm no chemist but I think there's a possibility DMSO will sulfate it? 

 

What about ethanol? Thing is DMSO is said to be a good solvent for quercetin.


Edited by Nate-2004, 15 December 2017 - 08:26 PM.


#78 greenwich

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Posted 16 December 2017 - 03:57 AM

I think I'm going to focus on Metformin. I can get that, and my sister who is a medical researcher, just came back from a conference, and reported that the docs there were saying that soon everyone might be on it - proven antiaging effect.

 

Anyone following the rapamycin thread?



#79 Nate-2004

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Posted 16 December 2017 - 01:57 PM

Berberine is cheaper, easier to get and has very similar effects to metformin but it's less studied and nobody knows the mechanism of action on it.  I'd like to be able to get metformin but not sure how I can find a reliable and trustworthy and better yet, cheap source. Perhaps I can trick my doctor into prescribing it.



#80 Nate-2004

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Posted 18 December 2017 - 01:26 AM

Resveratrol has a real affinity for sulfur though, which is why there are at least two ways it can get sulfated in the gut. DMSO has a sulfur with two unbonded electrons... i'm no chemist but I think there's a possibility DMSO will sulfate it? 

 

Back to this, it's weird, I'm not sure if DMSO would destabilize resveratrol through sulfation or not, in vitro or in vivo, it's like it didn't even occur to a number of published authors out there, like this one.



#81 Rocket

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Posted 18 December 2017 - 06:25 PM

 

Resveratrol has a real affinity for sulfur though, which is why there are at least two ways it can get sulfated in the gut. DMSO has a sulfur with two unbonded electrons... i'm no chemist but I think there's a possibility DMSO will sulfate it? 

 

Back to this, it's weird, I'm not sure if DMSO would destabilize resveratrol through sulfation or not, in vitro or in vivo, it's like it didn't even occur to a number of published authors out there, like this one.

 

 

I think we need a pure R extract without any of the store bought impurities... Does such a compound exist for purchase?



#82 Nate-2004

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Posted 18 December 2017 - 07:20 PM

Doctor's Best, specifically (and only) this one that's 600mg each, is the only one I found with trans-resveratrol only and nothing else (aside from the silicon dioxide filler and veg capsule itself). If you put it under the tongue just be sure to mix it with ethanol first which is what I did yesterday. I did this along with quercetin and this time around, some dasatinib. 


Edited by Nate-2004, 18 December 2017 - 07:20 PM.

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#83 greenwich

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Posted 18 December 2017 - 07:38 PM

I think we need a pure R extract without any of the store bought impurities... Does such a compound exist for purchase?

I buy this one. NuSci Pure Resveratrol Powder Standardized Extracted from Polygonum Cuspidatum Root

It's pure trans-resveratrol powder with no fillers, no added ingredients.

Then I make my own pills using this capsule machine.


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#84 Nate-2004

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Posted 18 December 2017 - 07:50 PM

That's not trans-resveratrol, it's just resveratrol according to the label on the bottle, that's the problem I ran into with Bulksupplements. The Amazon description appears to either be wrong or the label is wrong. Bad sign. Someone said that resveratrol slowly degrades into trans-resveratrol but I dunno how true that is.


Edited by Nate-2004, 18 December 2017 - 07:51 PM.


#85 greenwich

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Posted 18 December 2017 - 09:29 PM

That's not trans-resveratrol, it's just resveratrol according to the label on the bottle, that's the problem I ran into with Bulksupplements. The Amazon description appears to either be wrong or the label is wrong. Bad sign. Someone said that resveratrol slowly degrades into trans-resveratrol but I dunno how true that is.

Correct me if I'm wrong, but isn't "resveratrol" just comprised of the Cis and Trans isomers? So when you consume "resveratrol", it is not wrong to say you are consuming trans-resveratrol.

Some manufacturers may claim 100% trans-resveratrol, and that means they claim there is zero Cis.

If it is true that Cis is only a byproduct of fermentation, then you would *only* expect to find it in Red Wine, and nowhere else -- all other sources should be 100% trans, naturally. I think that alcohol is used to obtain many extracts. I assume they use it to dissolve the resveratrol, and not induce fermentation. But if not, all extracts could have Cis too.

In any event, it's clear that you can get a healthy dose of trans-resveratrol from any non-fermented source.

 

Sources:

https://en.wikipedia...iki/Resveratrol

https://forum.bodybu...php?t=118963531


Edited by greenwich, 18 December 2017 - 09:30 PM.

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#86 RWhigham

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Posted 19 December 2017 - 12:06 AM

Berberine is cheaper, easier to get and has very similar effects to metformin but it's less studied and nobody knows the mechanism of action on it.  I'd like to be able to get metformin but not sure how I can find a reliable and trustworthy and better yet, cheap source. Perhaps I can trick my doctor into prescribing it.

Metformin goes well with rapamycin  ref

 

but as pointed out in  ref

Berberine is a strong inhibitor of the P450 family ref1 and will interfere with rapamycin clearance ref2.

 

Inhibiting rapamycin clearance will make it poisonous.


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#87 Rocket

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Posted 21 December 2017 - 01:54 AM

Well I've read the old bodybuilding forums and guys were actually injecting resveratrol and apparently it worked but the side effects caused weight loss. We've been beaten to the punch. One poster noted that SIRT expression was too high and was causing too much weight loss. Does SIRT expression cause weight loss? I don't like the sounds of that personally.

#88 sthira

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Posted 21 December 2017 - 03:00 AM

In any event, it's clear that you can get a healthy dose of trans-resveratrol from any non-fermented source.

Sources:
https://en.wikipedia...iki/Resveratrol
https://forum.bodybu...php?t=118963531

Hmm. A diet with more muscadine wine, vinegar, and roasted peanuts. I've heard worse.

http://phenol-explor.../polyphenol/592

Edited by sthira, 21 December 2017 - 03:02 AM.


#89 sensei

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Posted 21 December 2017 - 03:12 PM

Nice thought, but no, not so fast.


Actually, liposomal encapsulation has been shown to allow the drug to be delivered into the tissues -- the liposomal encapsulation allows passage through the bloodstream and into the cell through the cell membrane.

https://www.scienced...cience/liposome

" Delivery of the drug is accomplished when the liposome fuses with the lipid membrane of a cell, releasing its contents into the cell cytoplasm."


This is why many now believe liposomal encapsulation is BETTER delivery system then IV.

Edited by sensei, 21 December 2017 - 03:13 PM.

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#90 Daniel Cooper

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Posted 21 December 2017 - 04:01 PM

Looks like liposomal resveratrol is readily available. Seems to be resveratrol + curcumin.  Amazon has several vendors.

 

 

 


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