65 replies to this topic

[Logic]

A very interesting chapter from a book:
http://cdn.intechope...on_activity.pdf

The document needs summarising with the different plant derivatives listed in order of potency.
I'll will get to that later.

The whole book here:
http://www.intechope...d/glycosylation

Edited by Logic, 07 May 2013 - 10:43 PM.

[YOLF]

Sounds interesting.

[solarfingers]

Niner, I found this on the Sens website. Is this what you are referencing?

http://www.sens.org/...o-sens-research

Yes, that's basically "the list". [...] If a genie popped out of a bottle and offered me one wish, I'd ask for a good AGE breaker.

Very interesting... I guess the problem for most of us 10-15 years is a very long time when you turn 50+. It would be prudent for me to keep my eyes on the technology and look for things that are known to work (even if on a small scale). It seems to be plausible that Astragalus aides in promoting new stem cells. That's another plus. c60 also can be instrumental in dealing with the problem of ROS. Could it be possible that c60-oo may cause some cross-linking when it passes between cells? Does the delivery of oo-lipids help soften and help the c60 carry this aggregated stuff away? I might be stretching here but have any of our c60-oo rat friends reported a decrease in aches and pains, or is this not a sign of AGE?

Edited by Michael, 22 October 2013 - 08:03 PM.

[niner]

If a genie popped out of a bottle and offered me one wish, I'd ask for a good AGE breaker.

Does the delivery of oo-lipids help soften and help the c60 carry this aggregated stuff away? I might be stretching here but have any of our c60-oo rat friends reported a decrease in aches and pains, or is this not a sign of AGE?

I really don't see any mechanism whereby c60 could cause crosslinking of structural proteins in the way that AGEs do. I also don't see any way that it would help to remove aggregates. Aches and pains are mostly inflammation, and chronic inflammation has a significant ROS component. I've noticed some reduction in aches and pains, as well as a reduction in inflammatory skin conditions. We've seen some indications that C60-oo might be resulting in stem cell activity, possibly through rescuing failed differentiation attempts, which are dependent on the cell switching from glycolysis to OXPHOS. C60-oo appears to improve the efficiency of OXPHOS.

Edited by Michael, 22 October 2013 - 08:04 PM.

[solarfingers]

I know we are getting off the topic of Astragolus and Telomeres but just to close the loop on my thinking, this looks like it might be an interesting read:
Natural inhibitors of advanced glycation end-products

I'm not quite ready to shell out $35.00 but it does look like an interesting article...

Also this:

http://morelife.org/...rs/14568010.pdf

And this also:

http://www.hindawi.c...am/2012/598638/

In conclusion, our study showed that Origanum majorana was effective in inhibiting the formation of AGEs. The antiglycation activities of O. majorana were attributed in part to their antioxidant activity and its abilities to scavenge reactive carbonyls. The ability of OM to react with carbonyls was the major mechanism for protein glycation inhibition. Furthermore, OM alleviated oxidative stress under diabetic conditions through the inhibition of lipid peroxidation, prevent and/or delay the onset renal damage. These results suggested that OM might prevent or improve the AGE associated chronic conditions. Therefore, O. majorana could be a candidate for use in studies looking at the effects of natural herbal complement in the prevention of diabetes complications, since it possesses both antioxidant and antyglycation activities.

This site suggests:

Advanced Glycation End Product (AGE) inhibitors
Specific Recommendations:

• carnosine / alpha lipoic acid / acetyl-l-carnitine / ginseng / gymnema / chromium / Metformin / l-arginine
• If you do a search of "Aminoguanidine pimagedine", several sites claim they are the same thing. Aminoguanidine is available at International Anti-aging Systems

[Logic]

Solarfingers you seem to really be enjoying learning all this?

Linked is an excellent full paper that explains Glycation well and can be used to create a plant derived AGE stack.
http://www.longecity...aminoguanidine/

Also it seems that chelationis a fundamental mechanism of action of AGE inhibitors and breakers:
http://www.longecity...rapy-with-edta/

[solarfingers]

Solarfingers you seem to really be enjoying learning all this?

Linked is an excellent full paper that explains Glycation well and can be used to create a plant derived AGE stack.
http://www.longecity...aminoguanidine/

Also it seems that chelationis a fundamental mechanism of action of AGE inhibitors and breakers:
http://www.longecity...rapy-with-edta/

Yes, I find microbiology fascinating, especially with the prospects of living a healthier life. An AGE stack! Now that does have my attention.

Thank you Logic!

[sthira]

Linked is an excellent full paper that explains Glycation well and can be used to create a plant derived AGE stack.
http://www.longecity...aminoguanidine/

Thanks for the book chapter. The writing shows the intense complexities of food and biology, and why there are few simple answers. And it also highlights the importance of eating a wide variety of fruits and vegetables. It'd be interesting to complie a Best Of List among the fruits and vegetables, herbs and spices that tend to contain potent AGE disruptors.

[solarfingers]

With the resources on this page I have verified the following are easily obtainable AGE inhibitors:

Chrysanthemum flower (morifolium) extract
Green Tea Extract
Cats Claw Root - procyanidin B2
Carnosine
Alpha Lipoic Acid

I could not find an article directly identifying the others or they were not easily accessible. Can anyone else add to this list with references? What I'm looking for specifically are those things in nature that give you more bang to the buck...

Thanks

Edited by solarfingers, 04 June 2013 - 03:04 AM.

[Logic]

Yes, I find microbiology fascinating, especially with the prospects of living a healthier life. An AGE stack! Now that does have my attention.

Thank you Logic!

Its a pleasure Solarfingers. I am glad that book chapter is getting a bit of the attention I think it deserves at last!
It does need someone more qualified than myself to read it to come up with a proper stack:
"The devil is in the dosage" and one has to look at synergies, contra-indications, etc.

One very interesting substance rumoured (Chinese paper?) to be an AGE breaker of the worst type of AGE is 2, 3, 5, 4'-tetrahydroxystilbene from Fo-ti or He shou wu.

Here is another nice article/summary from the 2nd link posted:
http://www.drzarkov.com/blog/?p=109

I feel that metal chelators need more looking at as AGE breakers too. They make up a large part of AGEs and perhaps removing them causes the break up..?

[solarfingers]

He Shou Wu is a very obtainable product... My favorite vendor, Swanson caries it and it appears to be quite inexpensive

Swanson Fo-Ti - $1.89 for one bottle 500 mg 60 Caps

Herb Pharm Ho Shou Wu Liquid Herbal Extract Extract - 1 fl oz $9.59

I'm with you that I'm no bio-chemist so more information would be needed to create any kind of stack. Are there any natural metal chelators? So far, from what I can tell, this is a very risky therapy. It would be great if we could find something to break the cross-links in nature because then we might be looking at AGE reversal and not just inhibition. I haven't seen anything like that yet so I'm looking at prevention as being my best hope for the future...

Perhaps a moderator can move these last posts to an AGEs appropriate thread. I think this might be useful.

Thanks...

Edited by solarfingers, 04 June 2013 - 02:12 PM.

[Logic]

Ah; here is the thread on 2,3,5,4'-tetrahydroxystilbene and Alagebrium/ALT-711 I was talking about:
http://www.longecity...gebriumalt-711/

There are some natural metal chelators. Garlic comes to mind, and the thread I linked:
http://www.longecity...rapy-with-edta/
has links worth following too:

Safe chelation of Mercury/Cadmium/Iron/Lead
http://www.longecity...admiumironlead/

Preventative Heavy Metal Detoxification
http://www.longecity...detoxification/

[solarfingers]

I'm suggesting that the AGEs posts be placed in Logic's thread...

http://www.longecity...aminoguanidine/

[solarfingers]

Reducing AGE levels – preventing retinopathy, renal damage, etc., even in the healthy – benfotiamine can undo damage, substantially improving nerve function while profoundly reducing pain.

"Benfotiamine is widely regarded as safer than the already-safe vitamin B-1 it is derived from."

Benfotiamine is a readily available supplement. Should be added to the list. It looks to be a promising AGE inhibitor and can undo AGE related damage.

Found this quick reference in the link Logic sent me...

Edited by solarfingers, 04 June 2013 - 06:53 PM.

[solarfingers]

Notice that Benfotiamine and L-Carnosine are both Inhibitors and Breakers with low risk. PABA has low to moderate risk factor. I like it when I find supplements that do double duty as does L-Carnosine. Carnosine has also been demonstrated to extend cellular life through it's ability to rejuvenate cells approaching senescence. This is what I call more bang for the buck. Is there any question we all should be taking L-Carnosine if we are taking this business seriously?

Edited by solarfingers, 04 June 2013 - 07:04 PM.

[zen]

He Shou Wu is a very obtainable product... My favorite vendor, Swanson caries it and it appears to be quite inexpensive

Swanson Fo-Ti - $1.89 for one bottle 500 mg 60 Caps

Herb Pharm Ho Shou Wu Liquid Herbal Extract Extract - 1 fl oz $9.59

Thanks...

Just FYI. I used to buy Swanson's Fo-Ti but after doing some more research I decided to switch to the processed He Shou Wu. The source I use is http://www.activeher...uct_Code=AH607E

[Logic]

Notice that Benfotiamine and L-Carnosine are both Inhibitors and Breakers with low risk. PABA has low to moderate risk factor. I like it when I find supplements that do double duty as does L-Carnosine. Carnosine has also been demonstrated to extend cellular life through it's ability to rejuvenate cells approaching senescence. This is what I call more bang for the buck. Is there any question we all should be taking L-Carnosine if we are taking this business seriously?

There has been a huge debate here on increased cancer risk with Benfotiamine.
I still think its worth taking, but that's something one has to decide for one's self
http://www.longecity...ncer-risk-quit/

It may be cheaper to take Beta-Alanine than L-Carnosine:
http://www.longecity...vs-l-carnosine/

As you can see the whole life extension subject is... complex and in its infancy.
Welcome to the club!

Edited by Logic, 04 June 2013 - 11:55 PM.

[niner]

Notice that Benfotiamine and L-Carnosine are both Inhibitors and Breakers with low risk. PABA has low to moderate risk factor. I like it when I find supplements that do double duty as does L-Carnosine. Carnosine has also been demonstrated to extend cellular life through it's ability to rejuvenate cells approaching senescence. This is what I call more bang for the buck. Is there any question we all should be taking L-Carnosine if we are taking this business seriously?

Michael Rae has advocated quitting benfotiamine due to a possible cancer risk. I've never looked into PABA, but my recollection is that it's a compound with some issues. I wonder what "moderate risk" means? Carnosine is probably not harmful, but it's expensive and our bodies are loaded with carnosinases that quickly chew it up. It's certainly good for cells in a Petri dish, but I'm suspicious that the bioavailability will be too low to do much in vivo. It would be nice to see some human data that showed a benefit. It's possible this exists- I haven't looked at this of late, but I don't remember seeing it. Anyone know?

Here's a recent paper on modified carnosines, which should have better bioavailability:

Amino Acids. 2012 Jul;43(1):111-26. doi: 10.1007/s00726-012-1224-z.
Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs.
Vistoli G, Carini M, Aldini G.

Department of Pharmaceutical Sciences Pietro Pratesi, Università degli Studi di Milano, via Mangiagalli 25, 20133 Milan, Italy.

The ability of carnosine to prevent advanced glycoxidation end products (AGEs) and advanced lipoxidation end products (ALEs) formation, on the one hand, and the convincing evidence that these compounds act as pathogenetic factors, on the other hand, strongly support carnosine as a promising therapeutic agent for oxidative-based diseases. The mechanism/s by which carnosine inhibits AGEs and ALEs is still under investigation but an emerging hypothesis is that carnosine acts by deactivating the AGEs and ALEs precursors and in particular the reactive carbonyl species (RCS) generated by both lipid and sugar oxidation. The ability of carnosine to inhibit AGEs and ALEs formation and the corresponding biological effects has been demonstrated in several in vitro studies and in some animal models. However, such effects are in line of principle, limited in humans, due to the effect of serum carnosinase (absent in rodents), which catalyzes the carnosine hydrolysis to its constitutive amino acids. Such a limitation has prompted a great interest in the design of carnosine derivatives, which maintaining (or improving) the reactivity with RCS, are more resistant to carnosinase. The present paper intends to critically review the most recent studies oriented to obtaining carnosine derivatives, optimized in terms of reactivity with RCS, selectivity (no reaction with physiological aldehydes) and the pharmacokinetic profile (mainly through an enhanced resistance to carnosinase hydrolysis). The review also includes a brief description of AGEs and ALEs as drug targets and the evidence so far reported regarding the ability of carnosine as inhibitor of AGEs and ALEs formation and the proposed reaction mechanisms.

PMID: 22286834

N-acetylcarnosine sounds pretty promising. You can get it (for $400/gram) in the form of eyedrops. These have been shown to reverse cataracts. I haven't seen an oral version, but I'm sure you could buy the raw material in China or India for a hell of a lot less than 0.4 million dollars per kg.

Edit: I see that in the couple hours this post sat around in the editor while I did other things, Logic posted the cancer thing. FWIW, I'm not a user of benfotiamine or carnosine.

Edited by niner, 05 June 2013 - 12:45 AM.

[zen]

N-acetylcarnosine sounds pretty promising. You can get it (for $400/gram) in the form of eyedrops. These have been shown to reverse cataracts. I haven't seen an oral version, but I'm sure you could buy the raw material in China or India for a hell of a lot less than 0.4 million dollars per kg.

I did a quick search and found it here http://purebulk.com/...ine-powder.html - definitely less than 0.4 million dollars per kg

[niner]

You can find it for even less (a lot less!) on alibaba. One of the vendors with a 1kg minimum order prices it from $180-250/kg, depending on grade.

[solarfingers]

When carnosine and blueberry were combined, the growth promotion (increased bone marrow cell proliferation) observed was 83%.

This article is something else I am pondering concerning carnosine. It seems to be helpful in stem cell proliferation when combined with blueberry leaf extract. Perhaps what we need to find is something which when combined with carnosine will make it more effective on AGE. The other agents in this study: green tea, catechin, and vitamin D3 were also known to raise bone marrow cell proliferation.

"Synergistic stimulatory effect of extracts and compounds on proliferation. To determine if the extracts and compounds displayed a synergistic effect on cell proliferation, we cultured human bone marrow cells with different combinations of the extracts and compounds. We also cultured the bone marrow cells with the individual extracts and compounds at the highest doses determined to promote the greatest amount of proliferation. The positive control, hGM-CSF displayed 48.3 7.4% proliferation, whereas blueberry, catechin, carnosine, green tea, and vitamin D3 alone did not cause proliferation in a significantly different manner. However, the combination of extracts and compounds resulted in a greater percentage of proliferation than observed with the individual extracts and compounds. For example, blueberry/vitamin D3 exhibited a 62% increase in proliferation, blueberry/catechin a 70% increase, and blueberry/carnosine with the greatest synergistic affect of 83% (Fig. 2A). Blueberry/green tea, blueberry/vitamin D3/green tea, and blueberry/vitamin D3/green tea/carnosine also displayed significant increases in proliferation of 56%, 72%, and 70% respectively."

"... Of all the compounds tested, blueberry extract most consistently produced significant proliferation when combined with the other compounds."

I think the big question is, "What is it about carnosine that made the blueberry extract more potent than the others?"

Green Tea seems to be on our list of AGE inhibitors as well...

"... it (Carnosine) is responsible for a variety of activities related to the detoxification of the body from free radical species and the by-products of membrane lipids peroxidation, but recent studies have shown that this small molecule also has membrane-protecting activity, proton buffering capacity, formation of complexes with transition metals, and regulation of macrophage function....

In particular, it has been recently demonstrated that carnosine is a potent and selective scavenger of alpha,beta-unsaturated aldehydes, typical by-products of membrane lipids peroxidation and considered second messengers of the oxidative stress, and inhibits aldehyde-induced protein-protein and DNA-protein cross-linking in neurodegenerative disorders..."

N-acetyl L-Carnosine

"NALC is found as a product of carnosine systhesis in mammalian cardiac and skeletal musclesR and brainR. NALC has been administered to horses by naso-gastric tube at 70 mg/kg body weight with no negative side effectsR. This same study found that intravenous administration of NALC (at 20 mg/kg body weight) raised serum levels; naso-gastric administration did not. The reason for this is unknown, but since horses have a far different digestive system than humans (they also have no serum carnosinase enzyme) and acetylated amino acids are generally as well or better absorbed than their non-acetylated forms, this result does not imply that NALC will not be absorbed from the GI tract by humans. Still, bioavailability results for NALC in humans is currently unproven and needed."

"[NALC] can act as a time release (carrier) stable version of L-carnosine during application in ophthalmic pharmaceutical and cosmetics formulations which include lubricants. ..."An important chemical difference between carnosine and Nacetylcarnosine is that carnosine is relatively insoluble in lipids (fats and fatty compounds), whereas N-acetylcarnosine is relatively soluble in lipids (as well as in water). This means that N-acetylcarnosine may pass through the lipid membranes of the corneal and skin cells more easily than carnosine, and may thereby gain access more readily to the cells interior, which is primarily aqueous. N-acetylcarnosine can be gradually broken down to carnosine which then exerts its beneficial effects."

Perhaps we need to be looking at N-acetyl L-Carnosine...

One scientist responds in this post that Carnosine is it is a potent antioxidant, it helps to chelate ionic metals (i.e. flush toxins from the body)...

Edited by solarfingers, 05 June 2013 - 02:58 AM.

[solarfingers]

As far as bio-availability is concerned, I am wondering if dissolving N-acetyl L-Carnosine in Olive Oil as we do C60 might increase bio-availability. It is an expensive product yet L-Carnosine is insoluble in lipids... Could Olive Oil act as a better carrier of Carnosine and take it further into the cells. Does anyone have any thoughts on this?

[niner]

As far as bio-availability is concerned, I am wondering if dissolving N-acetyl L-Carnosine in Olive Oil as we do C60 might increase bio-availability. It is an expensive product yet L-Carnosine is insoluble in lipids... Could Olive Oil act as a better carrier of Carnosine and take it further into the cells. Does anyone have any thoughts on this?

I don't think that olive oil would help. Carnosine and acetyl carnosine are both water soluble, and that is a good thing for bioavailability. Carnosine's bioavailability problems aren't caused by poor absorption- it actually gets in fine. The problem is that systemic carnosinases will munch it up as soon as it gets in. The acetylated version purportedly gets around this problem, though I've yet to see pharmacokinetic data on it.

[niner]

Regarding carnosine (and various other supplements) as stem cell proliferation agents, in that experiment, cells were soaked in various concentrations of the compounds for 72 hours. That's a long time to be maintaining a 20 uM concentration of carnosine, given the existence of carnosinase. You really have to take these in vitro experiments with a grain of salt. The authors of that paper had a conflict of interest listed. They were all founders of, or consultants to some nutraceutical company.

I'm hoping to see some solid evidence of benefit for carnosine or NALC supplementation in humans.

[cuprous]

Notice that Benfotiamine and L-Carnosine are both Inhibitors and Breakers with low risk. PABA has low to moderate risk factor. I like it when I find supplements that do double duty as does L-Carnosine. Carnosine has also been demonstrated to extend cellular life through it's ability to rejuvenate cells approaching senescence. This is what I call more bang for the buck. Is there any question we all should be taking L-Carnosine if we are taking this business seriously?

I've been taking 500mg daily for this very reason. The question is of course what's an appropriate dosage. Will 500mg do anything? Or are there metabolic pathways that will rapidly utilize this amount before it can float around and do good vis a vis AGE breaking?

[solarfingers]

This is one of the reasons I suspected that suspending in Olive Oil lipid might prevent it from being used up before it can get to the places we want it. If C60 can get into areas it usually wouldn't via Olive Oil why wouldn't the same be true for N-acetyl L-Carnosine? If we dissolve in water isn't it treated differently going through the digestive track? I trust Niner's opinion on these things however. Yes, at what level are we saturating the body with so much Carnosine that carnosinases can't use it up before we get the benefit of cross-link breakage? On the other hand it is know to stabilize cells and rescue them from senescence. I believe this has been demonstrated satisfactorily in the lab. How is it we doubt it is available long enough to accomplish one task yet not another? So many questions... I do think that a safe stack if for no other reason as inhibiting AGE would be:

Green Tea Extract
L-Carnosie
Alpha Lipoic Acid

They are comparatively available, inexpensive and perform other useful functions. The only caution should be with the Alpha Lipoic Acid for pregnant women and those who are dealing with a glycol issue such as diabetes.

[solarfingers]

Ah; here is the thread on 2,3,5,4'-tetrahydroxystilbene and Alagebrium/ALT-711 I was talking about:
http://www.longecity...gebriumalt-711/

Alagebrium looks interesting...

"So far, the safety profile of the drug appears to be excellent in human subjects. However, in December 2004, a study feeding alagebrium to lab rats for two years, found an increased rate of liver cell alterations in male rats, but not the females. This strain of lab rat (Sprague-Dawley) often develops liver cell alterations spontaneously, without drugs. The increased rate is comparable to effects caused in Sprague-Dawley rats by other, already approved drugs, such as the statins. These abnormalities are not necessarily expected in humans. Following further study, FDA allowed clinical trials to proceed.
No harmful interactions with other drugs have been observed. Any subjects who had been already taking other blood pressure medications continued on their previous medications in addition to taking alagebrium. Benefits of alagebrium were observed in addition to any benefits from the other blood pressure medications.
In December 2004, Synvista Therapeutics (Alteon) announced a phase 2 clinical trial of alagebrium to reverse erectile dysfunction. Subjects were slated to be taking 200 mg, once per day. "

[niner]

This is one of the reasons I suspected that suspending in Olive Oil lipid might prevent it from being used up before it can get to the places we want it. If C60 can get into areas it usually wouldn't via Olive Oil why wouldn't the same be true for N-acetyl L-Carnosine? If we dissolve in water isn't it treated differently going through the digestive track? I trust Niner's opinion on these things however. Yes, at what level are we saturating the body with so much Carnosine that carnosinases can't use it up before we get the benefit of cross-link breakage? On the other hand it is know to stabilize cells and rescue them from senescence. I believe this has been demonstrated satisfactorily in the lab. How is it we doubt it is available long enough to accomplish one task yet not another? So many questions... I do think that a safe stack if for no other reason as inhibiting AGE would be:

Green Tea Extract
L-Carnosie
Alpha Lipoic Acid

They are comparatively available, inexpensive and perform other useful functions. The only caution should be with the Alpha Lipoic Acid for pregnant women and those who are dealing with a glycol issue such as diabetes.

The reason that olive oil gets c60 into the body so well is that c60 isn't just dissolving in the oil, it actually reacts with it, forming a new molecule where one or more fatty acids from the olive oil are covalently bound to the c60. This new molecule has very good solubility in olive oil, compared to pristine c60, which does dissolve to a very small extent. The best case scenario for drug bioavailability would be a compound that is soluble in water, and since NALC has good water solubility (probably better than in oil), that would be the preferred route. If the oil solubility is high enough, and you took it that way, it would eventually get into the system, at which point it would still have to deal with carnosinase. There are certainly compounds that have poor water solubility, like resveratrol, and can use some help getting in. One trick is to use a cyclodextrin, a cyclic molecule that has a hydrophobic inner cavity (a hospitable place for a hydrophobic molecule like resveratrol) and a hydrophilic outer surface. The cyclodextrin acts as a "cloak", shepherding the resveratrol through the hydrophilic GI tract, and eventually disgorging it somewhere along the way. It improves resveratrol's bioavailability, although like carnosine, resveratrol is rapidly metabolized.

GTE, carnosine, and ALA are all pretty safe. GTE can cause liver issues if you overdo it. ALA is actually pretty good in diabetes. It will reduce blood sugar levels (although sometimes that's not what you want) and is also helpful in certain diabetic complications. I don't know of any problems with carnosine, other than a lack of evidence that the magic really happens in vivo. I've taken all of these at some point in my life, although today the only one I use is GTE.

[solarfingers]

Thanks Niner,

That's a very clear explanation. Most sites recommend no more than 1,000 mg of carnosine. Do you think it would benefit to take more, say twice that much?

[Luddist]

Bumpin this up. How would the potency of the various plants and extracts be quantified for ranking?