635 replies to this topic

[niner]

If the large effects generated by Sensei dosing levels (10 - 20 x norm) are replicated how does this support/undermine the various theories of C60oo? In particular, I was under the impression that the current general dosing levels delivered more than enough of the super anti-oxidant to get the job done. Would it therefore be likely that c60oo is more than just a mitochondrial free-radical sponge?

 

Yes, it's almost certainly more than a free radical sponge.  Various fullerene compounds have been shown to have extremely important receptor-mediated effects.  Many of the compounds that have been optimized to elicit those effects use c70 rather than c60.  C70 is the primary contaminant in commercial c60, so if you are using 99.5% c60, most of the other 0.5% is c70.  One of those c70 compounds has been shown to grow hair on human skin in culture, as well as rodent models.  Thus it's possible that the hair-growing effect sensei is reporting is due to a contaminant in the c60oo, which would explain the need for large doses.  It would certainly be possible to make c70oo, in fact Turnbuckle did that a year or two ago.

[sensei]

 

 

Yes, it's almost certainly more than a free radical sponge.  Various fullerene compounds have been shown to have extremely important receptor-mediated effects.  Many of the compounds that have been optimized to elicit those effects use c70 rather than c60.  C70 is the primary contaminant in commercial c60, so if you are using 99.5% c60, most of the other 0.5% is c70.  One of those c70 compounds has been shown to grow hair on human skin in culture, as well as rodent models.  Thus it's possible that the hair-growing effect sensei is reporting is due to a contaminant in the c60oo, which would explain the need for large doses.  It would certainly be possible to make c70oo, in fact Turnbuckle did that a year or two ago.

 

 

I read the whole paper and could not determine C60 or C70 -- where did you get info it is C70? -- The Figure one in the .pdf of the study paper looks like the center molecule is C60 (spherical) as opposed to C70 (rugby ball)

 

Also, C60 NOT c70 has been found to cause differentiation of adipose derived stem cells into osteoblasts, and other tissues

 

I believe that C60 has an effect on stem cell differentiation, and may also act in a way that reverts older cells to a younger cell phase.  The effect on hair could simply be reversion from telogen to anagen

 

As far as the level of contamination -- I have yet to reach a total of 3 grams C60, at 5 parts in 10,000 that would only equal a total of 1.5 mg C70 over the entire 8 months I have been ingesting C60.

 

Not to mention that we know C60 forms inclusion compounds with AT LEAST ONE molecule (cyclodextrin) that has been proven to remove lipofuscin from cells.

 

Fullerenes explicitly C60 also inhibit the allergic response in the human body

 

http://www.jyi.org/i...ergic-response/

 

I believe C60 also strongly inhibits inflammatory mechanisms as well.

Edited by sensei, 14 January 2015 - 09:48 PM.

[niner]

 

Yes, it's almost certainly more than a free radical sponge.  Various fullerene compounds have been shown to have extremely important receptor-mediated effects.  Many of the compounds that have been optimized to elicit those effects use c70 rather than c60.  C70 is the primary contaminant in commercial c60, so if you are using 99.5% c60, most of the other 0.5% is c70.  One of those c70 compounds has been shown to grow hair on human skin in culture, as well as rodent models.  Thus it's possible that the hair-growing effect sensei is reporting is due to a contaminant in the c60oo, which would explain the need for large doses.  It would certainly be possible to make c70oo, in fact Turnbuckle did that a year or two ago.

 

I read the whole paper and could not determine C60 or C70 -- where did you get info it is C70? -- The Figure one in the .pdf of the study paper looks like the center molecule is C60 (spherical) as opposed to C70 (rugby ball)

 

Also, C60 NOT c70 has been found to cause differentiation of adipose derived stem cells into osteoblasts, and other tissues

 

I believe that C60 has an effect on stem cell differentiation, and may also act in a way that reverts older cells to a younger cell phase.  The effect on hair could simply be reversion from telogen to anagen

 

As far as the level of contamination -- I have yet to reach a total of 3 grams C60, at 5 parts in 10,000 that would only equal a total of 1.5 mg C70 over the entire 8 months I have been ingesting C60.

 

Well, in the patent they say "c60 or c70", but maybe I'm confusing that with their mast cell compounds.  I'm not sure that the commercial providers are using c60 that's as pure as they claim.  They might be, but I don't think anyone has tested it.

[sensei]

 

 

Well, in the patent they say "c60 or c70", but maybe I'm confusing that with their mast cell compounds.  I'm not sure that the commercial providers are using c60 that's as pure as they claim.  They might be, but I don't think anyone has tested it.

 

 

 without naming names at least one commercial preparer uses 99.95% purchased from ses research

 

ses research also state that they use the 99.95% pure oven dried C60 in their own C60OO product

 

I just looked 

 

The patent calls out both polyhydroxylated C60 and so strange C70 compounds as potentiating growth

 

The follicular genesis however was caused by a C70 compound (at least in the patent you cited)

 

funny enough, the study stated DMSO as a vehicle, while the patent states phosphate buffered saline == maybe not the same group

Edited by sensei, 14 January 2015 - 10:18 PM.

[HighDesertWizard]

The C60s found in Macrophages in the Spleen have not been discussed much as a potential Explanation of the Baati paper's Longevity Result. I've found a few studies that suggest the Spleen-C60 phenomenon may not be a trivial fact vis-a-vis that Result.

 

I don't have a complete and coherent Explanation of that result centered on those C60 laden Spleen Macrophages. What I have in mind are a set of Evidence Nodes that may be important to establishing such an Explanation.

 

Evidence Nodes

• First, the data in Table 2...

 

• Among other functions, the spleen is a reservoir of Monocytes that become dendritic cells and macrophages in the circulation.

The spleen is an organ found in virtually all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter...It is possible to remove the spleen without jeopardizing life. A study published in 2009 using mice found that the spleen contains, in its reserve, half of the body's monocytes within the red pulp.[5] These monocytes, upon moving to injured tissue (such as the heart), turn into dendritic cells and macrophages while promoting tissue healing.

• Among other studies, Identification of Splenic Reservoir Monocytes and Their Deployment to Inflammatory Sites showed that half of the Monocytes that may eventually wind up in the circulation are held in reserve in the spleen . 

Here we show that bona fide undifferentiated monocytes reside in the spleen and outnumber their equivalents in circulation. The reservoir monocytes assemble in clusters in the cords of the subcapsular red pulp and are distinct from macrophages and DCs. In response to ischemic myocardial injury, splenic monocytes increase their motility, exit the spleen en masse, accumulate in injured tissue, and participate in wound healing. These observations uncover a role for the spleen as a site for storage and rapid deployment of monocytes and identify splenic monocytes as a resource that the body exploits to regulate inflammation.

• The transformation of Monocytes to Macrophages is not simple and this complexity has been described in several studies. Nevertheless, Monocytes [do] Become Macrophages...: 

We concluded that macrophages in stab injuries of the spinal cord of mice are derived from blood monocytes. 

• We know that tumors are a frequent cause of death in mice. And it turns out that spleen reserved tumor-associated macrophages play some non-trivial role in tumor progression.

Tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) can control cancer growth and exist in almost all solid neoplasms. The cells are known to descend from immature monocytic and granulocytic cells, respectively, which are produced in the bone marrow. However, the spleen is also a recently identified reservoir of monocytes, which can play a significant role in the inflammatory response that follows acute injury. Here, we evaluated the role of the splenic reservoir in a genetic mouse model of lung adenocarcinoma driven by activation of oncogenic Kras and inactivation of p53. We found that high numbers of TAM and TAN precursors physically relocated from the spleen to the tumor stroma, and that recruitment of tumor-promoting spleen-derived TAMs required signaling of the chemokine receptor CCR2. Also, removal of the spleen, either before or after tumor initiation, reduced TAM and TAN responses significantly and delayed tumor growth. The mechanism by which the spleen was able to maintain its reservoir capacity throughout tumor progression involved, in part, local accumulation in the splenic red pulp of typically rare extramedullary hematopoietic stem and progenitor cells, notably granulocyte and macrophage progenitors, which produced CD11b+ Ly-6Chi monocytic and CD11b+ Ly-6Ghi granulocytic cells locally. Splenic granulocyte and macrophage progenitors and their descendants were likewise identified in clinical specimens. The present study sheds light on the origins of TAMs and TANs, and positions the spleen as an important extramedullary site, which can continuously supply growing tumors with these cells.

• Several recent studies have highlighted the role of Young vs. Old Blood Circulation factors as being important for aging. Harold Katcher provides a list of these studies and comes to an extreme conclusion of what this means for longevity science.

Given the importance of 1) young vs. old circulation system factors to aging, 2) half of macrophages that may eventually find their way into the circulation system being held in reserve in the spleen, 3) the large presence of spleen macrophages being laden with C60s in the Baati study...

 

It seems reasonable to me that we ought more to explore these spleen macrophages as being potentially important to the Baati study result.

 

To be clear... Including this data about spleen macrophages containing C60s in an Explanation of the Baati study result is not inconsistent with other Explanations already proposed. 1) Macrophages express pro-inflammatory elements and ROS is related to inflammation. 2) The new Circulation oriented studies highlighted by Katcher suggest an epigenetic trigger.

 

Thoughts?

Edited by HighDesertWizard, 18 January 2015 - 10:06 PM.

[Kalliste]

Well this is a very interesting paper that I found today. It is posted in the Biosciencenews section, however I wanted to bring it here because it seems this might be related to C60.

 

 

Significance

Mechanistic studies of nontoxic hydrophilic carbon cluster nanoparticles show that they are able to accomplish the direct conversion of superoxide to dioxygen and hydrogen peroxide. This is accomplished faster than in most single-active-site enzymes, and it is precisely what dioxygen-deficient tissue needs in the face of injury where reactive oxygen species, particularly superoxide, overwhelm the natural enzymes required to remove superoxide. We confirm here that the hydrophilic carbon clusters are unreactive toward nitric oxide radical, which is a potent vasodilator that also has an important role in neurotransmission and cytoprotection. The mechanistic results help to explain the preclinical efficacy of these carbon nanoparticles in mitigating the deleterious effects of superoxide on traumatized tissue.

Abstract

Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms the scavenging ability of an organism. Here, we evaluated the carbon nanoparticle antioxidant properties of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs) by electron paramagnetic resonance (EPR) spectroscopy, oxygen electrode, and spectrophotometric assays. These carbon nanoparticles have 1 equivalent of stable radical and showed superoxide (O₂^•−) dismutase-like properties yet were inert to nitric oxide (NO^•) as well as peroxynitrite (ONOO⁻). Thus, PEG-HCCs can act as selective antioxidants that do not require regeneration by enzymes. Our steady-state kinetic assay using KO₂ and direct freeze-trap EPR to follow its decay removed the rate-limiting substrate provision, thus enabling determination of the remarkable intrinsic turnover numbers of O₂^•− to O₂ by PEG-HCCs at >20,000 s⁻¹. The major products of this catalytic turnover are O₂ and H₂O₂, making the PEG-HCCs a biomimetic superoxide dismutase.

 

http://www.pnas.org/...047112.abstract

[niner]

Thanks, Cosmical.  This is a good place to discuss that.  According to the Supporting Info, these are oxidized nanotubes that have been subsequently PEGylated.  I'm not sure that the structure is fully defined.  They sound like they are pretty great SOD mimetics.

[pone11]

Well this is a very interesting paper that I found today. It is posted in the Biosciencenews section, however I wanted to bring it here because it seems this might be related to C60.

 

 

Significance

Mechanistic studies of nontoxic hydrophilic carbon cluster nanoparticles show that they are able to accomplish the direct conversion of superoxide to dioxygen and hydrogen peroxide. This is accomplished faster than in most single-active-site enzymes, and it is precisely what dioxygen-deficient tissue needs in the face of injury where reactive oxygen species, particularly superoxide, overwhelm the natural enzymes required to remove superoxide. We confirm here that the hydrophilic carbon clusters are unreactive toward nitric oxide radical, which is a potent vasodilator that also has an important role in neurotransmission and cytoprotection. The mechanistic results help to explain the preclinical efficacy of these carbon nanoparticles in mitigating the deleterious effects of superoxide on traumatized tissue.

Abstract

Many diseases are associated with oxidative stress, which occurs when the production of reactive oxygen species (ROS) overwhelms the scavenging ability of an organism. Here, we evaluated the carbon nanoparticle antioxidant properties of poly(ethylene glycolated) hydrophilic carbon clusters (PEG-HCCs) by electron paramagnetic resonance (EPR) spectroscopy, oxygen electrode, and spectrophotometric assays. These carbon nanoparticles have 1 equivalent of stable radical and showed superoxide (O₂^•−) dismutase-like properties yet were inert to nitric oxide (NO^•) as well as peroxynitrite (ONOO⁻). Thus, PEG-HCCs can act as selective antioxidants that do not require regeneration by enzymes. Our steady-state kinetic assay using KO₂ and direct freeze-trap EPR to follow its decay removed the rate-limiting substrate provision, thus enabling determination of the remarkable intrinsic turnover numbers of O₂^•− to O₂ by PEG-HCCs at >20,000 s⁻¹. The major products of this catalytic turnover are O₂ and H₂O₂, making the PEG-HCCs a biomimetic superoxide dismutase.

 

http://www.pnas.org/...047112.abstract

 

This is fantastic stuff.   C60+OO may be a superoxide dismutase (SOD) mimic that is actually a superset of the endogenous SOD!  Wow.

 

Let's think this through to its logical conclusion.   The process in a human body is that superoxide is converted by SOD to Hydrogen Peroxide.   But it is *catalase* that then renders the H2O2 harmless!  You need BOTH of these, and both SOD and catalase decline as we age.

 

This has a direct implication for those of you taking C60+OO.  Doesn't it make sense for us to find a way to supplement catalase?  In theory, those of you taking C60+OO are simply substituting dangerous superoxide radicals for less dangerous but still dangerous H2O2.   If you could raise your catalase levels at the same time you supplement C60+OO, you should see a synergistic effect and might return your antioxidant repair to levels seen when you were younger.

 

There are catalase supplements such as this one:

http://www.amazon.co...duct/B008BASLD4

 

It certainly is not cheap.   I have seen research claiming that supplemental catalase improves recovery after exercise:

http://www.ncbi.nlm....pubmed/11003786

 

and that is the application I use it for.

 

The thought I had is could someone come up with a catalase supplement that is liposomal, using the same production technique people are using for homemade liposomal vitamin C?   The combination of the C60+OO with an effective catalase supplement might have a dramatic effect that goes beyond what C60+OO does on its own.

[niner]

This has a direct implication for those of you taking C60+OO.  Doesn't it make sense for us to find a way to supplement catalase?  In theory, those of you taking C60+OO are simply substituting dangerous superoxide radicals for less dangerous but still dangerous H2O2.   If you could raise your catalase levels at the same time you supplement C60+OO, you should see a synergistic effect and might return your antioxidant repair to levels seen when you were younger.

 

There are catalase supplements such as this one:

http://www.amazon.co...duct/B008BASLD4

 

It certainly is not cheap.   I have seen research claiming that supplemental catalase improves recovery after exercise:

http://www.ncbi.nlm....pubmed/11003786

 

and that is the application I use it for.

 

The thought I had is could someone come up with a catalase supplement that is liposomal, using the same production technique people are using for homemade liposomal vitamin C?   The combination of the C60+OO with an effective catalase supplement might have a dramatic effect that goes beyond what C60+OO does on its own.

 

A liposomal delivery system is an interesting idea.  It is widely believed that large proteins are not orally bioavailable, as a general rule.  The paper you linked isn't using oral delivery of catalase; it's applying a catalase solution directly to the muscle.  That bypasses the whole GI tract, where most protein degradation occurs, and also eliminates other forms of peptide metabolism and barriers to entry.   I doubt that anyone has measured an increased level of catalase in blood after taking pills like this.

[ambivalent]

So c60oo is generating excess Hydrogen Peroxide which we wish to remove via an increase in catalase? Won't glutathione do too? Here seems to be a way, well it works in elephant seals:

 

Results indicate that GSH biosynthesis increases with fasting and that contributes to counteracting hydroperoxide production, preventing oxidative damage in fasting seals.

 

http://jeb.biologist...8/1294.full.pdf

 

 

 

 

 

Edited by ambivalent, 11 February 2015 - 04:15 AM.

[pone11]

 

This has a direct implication for those of you taking C60+OO.  Doesn't it make sense for us to find a way to supplement catalase?  In theory, those of you taking C60+OO are simply substituting dangerous superoxide radicals for less dangerous but still dangerous H2O2.   If you could raise your catalase levels at the same time you supplement C60+OO, you should see a synergistic effect and might return your antioxidant repair to levels seen when you were younger.

 

There are catalase supplements such as this one:

http://www.amazon.co...duct/B008BASLD4

 

It certainly is not cheap.   I have seen research claiming that supplemental catalase improves recovery after exercise:

http://www.ncbi.nlm....pubmed/11003786

 

and that is the application I use it for.

 

The thought I had is could someone come up with a catalase supplement that is liposomal, using the same production technique people are using for homemade liposomal vitamin C?   The combination of the C60+OO with an effective catalase supplement might have a dramatic effect that goes beyond what C60+OO does on its own.

 

A liposomal delivery system is an interesting idea.  It is widely believed that large proteins are not orally bioavailable, as a general rule.  The paper you linked isn't using oral delivery of catalase; it's applying a catalase solution directly to the muscle.  That bypasses the whole GI tract, where most protein degradation occurs, and also eliminates other forms of peptide metabolism and barriers to entry.   I doubt that anyone has measured an increased level of catalase in blood after taking pills like this.

 

 

I was aware of the digestive issue, which is why I am suggesting a liposomal delivery system.

[niner]

So c60oo is generating excess Hydrogen Peroxide which we wish to remove via an increase in catalase? Won't glutathione do too? Here seems to be a way, well it works in elephant seals:

 

Actually, we don't know that we have a problem.  Maybe the catalase we have is sufficient to handle the H2O2 that gets produced from superoxide.  I'd certainly rather have peroxide in my cells than radicals.  It's much less reactive.  Increasing catalase is probably beneficial in general, of course.  Exercise probably helps, hormetically.

[pone11]

 

So c60oo is generating excess Hydrogen Peroxide which we wish to remove via an increase in catalase? Won't glutathione do too? Here seems to be a way, well it works in elephant seals:

 

Actually, we don't know that we have a problem.  Maybe the catalase we have is sufficient to handle the H2O2 that gets produced from superoxide.  I'd certainly rather have peroxide in my cells than radicals.  It's much less reactive.  Increasing catalase is probably beneficial in general, of course.  Exercise probably helps, hormetically.

 

 

Agreed that H2O2 is better that the superoxide radical, and I think I made that point.  

 

Supplementing superoxide dismutase is normally problematic, as paradoxically the endogenous levels of SOD fall so sharply that it can result in even lower SOD levels with supplementation than without.   See for example:

https://www.jstage.j...5/53_5_608/_pdf

 

What excites me about the C60+OO reference is it suggests a way of supplementing endogenous SOD with an SOD mimic that might not lower endogenous SOD levels.   If it happens that way, it would be a huge huge win for C60+OO and might explain some of the effects people are seeing.

 

Catalase falls with age.   And interestingly organisms that are engineered with overexpression of catalase do live longer:

http://www.ncbi.nlm....pubmed/18067683

 

While you are right we probably cannot prove it, it is not a stretch to believe that an aging animal benefits from supplemental catalase IF:

 

1) It has a way to get into mitochondria.

 

2) It does not lower endogenous catalase levels.

 

I'm simply trying to flag this idea to the post on C60+OO being an SOD mimic, because if someone can engineer a solution to the catalase problem, I would expect a very synergistic effect with the C60+OO acting as an SOD mimic.

[ambivalent]

To balance (and close the subject off) the effect of fasting on seals' glutathione/hydrogen peroxide levels, a couple of papers showing that gluthianone levels decrease dramtically in fasted mice and remain the same in humans - though fasting conditions vary.

Edited by ambivalent, 11 February 2015 - 06:02 PM.

[niner]

Supplementing superoxide dismutase is normally problematic, as paradoxically the endogenous levels of SOD fall so sharply that it can result in even lower SOD levels with supplementation than without.   See for example:

https://www.jstage.j...5/53_5_608/_pdf

 

What excites me about the C60+OO reference is it suggests a way of supplementing endogenous SOD with an SOD mimic that might not lower endogenous SOD levels.   If it happens that way, it would be a huge huge win for C60+OO and might explain some of the effects people are seeing.

 

Catalase falls with age.   And interestingly organisms that are engineered with overexpression of catalase do live longer:

http://www.ncbi.nlm....pubmed/18067683

 

While you are right we probably cannot prove it, it is not a stretch to believe that an aging animal benefits from supplemental catalase IF:

 

1) It has a way to get into mitochondria.

 

2) It does not lower endogenous catalase levels.

 

I'm simply trying to flag this idea to the post on C60+OO being an SOD mimic, because if someone can engineer a solution to the catalase problem, I would expect a very synergistic effect with the C60+OO acting as an SOD mimic.

 

The pdf is interesting- it's a bit muddled by the mixtures of compounds they're using, but plant SOD with gliadin (aka gluten(!)), a product also known as GliSODin, looks like bad news.  They say that it's getting into the system through Peyer's patches, which seems odd.  Peyer's patches are supposed to present antigens to immune cells.  The idea that those antigens would be dumped wholesale into circulation seems wrong, but the gliadin/SOD was having a systemic effect, and clearly not a good one.   I'd like to know if other antioxidants have this kind of counterproductive effect.  Does C60oo do it too?  Baati's rat results suggest not, but I don't think anyone has measured before/after redox parameters.  It wouldn't be that hard to do.
 

[pone11]

 

Supplementing superoxide dismutase is normally problematic, as paradoxically the endogenous levels of SOD fall so sharply that it can result in even lower SOD levels with supplementation than without.   See for example:

https://www.jstage.j...5/53_5_608/_pdf

 

What excites me about the C60+OO reference is it suggests a way of supplementing endogenous SOD with an SOD mimic that might not lower endogenous SOD levels.   If it happens that way, it would be a huge huge win for C60+OO and might explain some of the effects people are seeing.

 

Catalase falls with age.   And interestingly organisms that are engineered with overexpression of catalase do live longer:

http://www.ncbi.nlm....pubmed/18067683

 

While you are right we probably cannot prove it, it is not a stretch to believe that an aging animal benefits from supplemental catalase IF:

 

1) It has a way to get into mitochondria.

 

2) It does not lower endogenous catalase levels.

 

I'm simply trying to flag this idea to the post on C60+OO being an SOD mimic, because if someone can engineer a solution to the catalase problem, I would expect a very synergistic effect with the C60+OO acting as an SOD mimic.

 

The pdf is interesting- it's a bit muddled by the mixtures of compounds they're using, but plant SOD with gliadin (aka gluten(!)), a product also known as GliSODin, looks like bad news.  They say that it's getting into the system through Peyer's patches, which seems odd.  Peyer's patches are supposed to present antigens to immune cells.  The idea that those antigens would be dumped wholesale into circulation seems wrong, but the gliadin/SOD was having a systemic effect, and clearly not a good one.   I'd like to know if other antioxidants have this kind of counterproductive effect.  Does C60oo do it too?  Baati's rat results suggest not, but I don't think anyone has measured before/after redox parameters.  It wouldn't be that hard to do.
 

 

So some of you hardcore C60+OO users should do us all a favor and test your SOD levels before and after supplementation.  There are panels like Genova Oxidative Stress 2.0 that make that measurement.   

 

The whole reason I got excited here was that the body might not see C60+OO as SOD and therefore would NOT regulate its endogenous supply.   The ability to mimic SOD might just be functional, so that C60 is performing a similar role and chemical conversion as SOD, but by some novel mechanism that the body cannot easily recognize and respond to.  That would make the superoxide to hydrogen peroxide conversion of C60+OO incremental to the same conversion done by the body's endogenous SOD supply.   

 

That's what I find exciting here.  C60 may be bypassing the body's endogenous regulation of SOD and therefore cheating the system into permanently higher effective conversion of superoxide radicals.    Match that to an increased catalase expression, and your ability to handle mitochondrial oxidative stress might return to levels you last saw when you were young.    You think people's reports of hair being less grey on C60 are exciting?   Match that to effectively higher catalase expression and watch the hair return back to its original color.   It's not a crazy hypothesis.

[sensei]

That's what I find exciting here.  C60 may be bypassing the body's endogenous regulation of SOD and therefore cheating the system into permanently higher effective conversion of superoxide radicals.    Match that to an increased catalase expression, and your ability to handle mitochondrial oxidative stress might return to levels you last saw when you were young.    You think people's reports of hair being less grey on C60 are exciting?   Match that to effectively higher catalase expression and watch the hair return back to its original color.   It's not a crazy hypothesis.

 

 

 

I question the idea of C60OO creating more hydrogen peroxide --  hydrogen peroxide is the causative agent in grey/white hair. Yet, I and others have seen decreased gray hair.

 

http://www.medicalne...cles/260089.php

 

There is also lots of evidence to the contrary -- carboxy-fullerenes have been found to protect cells specifically from H2O2 oxidative stress

 

Yin JJ, Lao F, Fu PP, Wamer WG, et al "The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials" Biomaterials 30 (2009) pp 611-621

 

 

 

Furthermore, I can attest that some of my hair is starting to return to the color I had decades ago -- head hair, eyebrows and beard.

 

To be clear

 

1. not all grey hair is gone, some stragglers remain

2. the change to more vibrant color of youth rather than dull of middle age is in some places

 

I am trying to find some older pictures that show beard color and hair color when I was younger. Most are pre-digital low res and I didn't keep a beard regularly.

 

If it does cause H2O2 -- it must also cause a massive upregulation in catalase -- as catalase reveses grey hair -- from the link above

 

"The researchers found that this massive build up of hydrogen peroxide can be reversed with a UVB-activated compound called PC-KUS, a modified pseudocatalase"

Edited by sensei, 12 February 2015 - 01:17 PM.

[niner]

 

The pdf is interesting- it's a bit muddled by the mixtures of compounds they're using, but plant SOD with gliadin (aka gluten(!)), a product also known as GliSODin, looks like bad news.  They say that it's getting into the system through Peyer's patches, which seems odd.  Peyer's patches are supposed to present antigens to immune cells.  The idea that those antigens would be dumped wholesale into circulation seems wrong, but the gliadin/SOD was having a systemic effect, and clearly not a good one.   I'd like to know if other antioxidants have this kind of counterproductive effect.  Does C60oo do it too?  Baati's rat results suggest not, but I don't think anyone has measured before/after redox parameters.  It wouldn't be that hard to do.

 

So some of you hardcore C60+OO users should do us all a favor and test your SOD levels before and after supplementation.  There are panels like Genova Oxidative Stress 2.0 that make that measurement.   

 

The whole reason I got excited here was that the body might not see C60+OO as SOD and therefore would NOT regulate its endogenous supply.   The ability to mimic SOD might just be functional, so that C60 is performing a similar role and chemical conversion as SOD, but by some novel mechanism that the body cannot easily recognize and respond to.  That would make the superoxide to hydrogen peroxide conversion of C60+OO incremental to the same conversion done by the body's endogenous SOD supply.   

That's what I find exciting here.  C60 may be bypassing the body's endogenous regulation of SOD and therefore cheating the system into permanently higher effective conversion of superoxide radicals.    Match that to an increased catalase expression, and your ability to handle mitochondrial oxidative stress might return to levels you last saw when you were young.    You think people's reports of hair being less grey on C60 are exciting?   Match that to effectively higher catalase expression and watch the hair return back to its original color.   It's not a crazy hypothesis.

 

C60oo is unlikely to influence SOD levels directly, but might influence them indirectly.  If it is reducing the amount of superoxide, then over time SOD levels may drop because they are not needed as much.  SOD levels, like a lot of enzymes, are probably regulated at least in part by substrate levels.

 

Early on, I looked into redox panels like Geronova's.  They're expensive.  It would be great if we could get some data; maybe someone knows an academic who's interested in this sort of thing, and could do animal experiments?  I'd really like to see human results, though.  We'd need to find c60-naive individuals, test them before and shortly after dosing, then dose for a considerable period and test again.  It would be quite a project.  It would be easier for us to do it, in the absence of a pesky Institutional Review Board, than for an academic to get a human trial going.  LongeCity is sitting on a large pile of cash, maybe this would be a good use of a bit of it?

 

Regarding H2O2, it is benign until it forms radical species.  These radicals can chain propagate and wreak all manner of havoc.  Catalase will safely dispatch peroxide, but maybe c60 is taking care of the problem after radical formation, by interrupting chain propagation.  This might explain how c60 could be having an effect on hair graying, despite the hypothetical possibility that it increases peroxide. 

 

Glutathione peroxidase is another way that peroxide can be cleared.  NAC, as a glutathione precursor, might amp up this pathway.  If you google NAC and hydrogen peroxide, you see a lot of results that suggest NAC has an effect on at least the consequences of H2O2, and perhaps the production of it.

[Logic]

I have a theory on one of the ways in which C60oo may be working:

ROS damages DNA.

PARP is instrumental in DNA repair.

PARP requires NAD+.

As the amount of ROS increase; the amount of NAD+ required by PARP increases, leaving less for SIRT etc. and its longevity effects.

 

ie: C60oo cuts the amount of ROS; leading to less DNA damage; leading to less need for PARP; leading to an increase in available NAD+ available for SIRTs etc; leading to the lifespan increase seen in Baati's experiment.

 

Thoughts?

 

 

[Nuke]

Just wondering, what is the chance of C60 being a catalyst also being able to break down H2O2? It should be easy enough to test for anyone with C60 and some H2O2 from the pharmacy.

 

When I was younger I had lots of fun with H2O2 and Mn02. Unfortunately I don't have C60 yet, otherwise I would test it myself.

[Logic]

I have a theory on one of the ways in which C60oo may be working:
ROS damages DNA.
PARP is instrumental in DNA repair.
PARP requires NAD+.
As the amount of ROS increase; the amount of NAD+ required by PARP increases, leaving less for SIRT etc. and its longevity effects.
 
ie: C60oo cuts the amount of ROS; leading to less DNA damage; leading to less need for PARP; leading to an increase in available NAD+ available for SIRTs etc; leading to the lifespan increase seen in Baati's experiment.
 
Thoughts?

 
No!? 
 
Ad to the above that C60oo lowering mitochondrially produced ROS, and thus protecting it fragile DNA also, as well as increasing SOD and/or glutathione in a positive feedback loop...
I think the pieces fit pretty nicely?

[pone11]

 

That's what I find exciting here.  C60 may be bypassing the body's endogenous regulation of SOD and therefore cheating the system into permanently higher effective conversion of superoxide radicals.    Match that to an increased catalase expression, and your ability to handle mitochondrial oxidative stress might return to levels you last saw when you were young.    You think people's reports of hair being less grey on C60 are exciting?   Match that to effectively higher catalase expression and watch the hair return back to its original color.   It's not a crazy hypothesis.

 

 

 

I question the idea of C60OO creating more hydrogen peroxide --  hydrogen peroxide is the causative agent in grey/white hair. Yet, I and others have seen decreased gray hair.

 

http://www.medicalne...cles/260089.php

 

There is also lots of evidence to the contrary -- carboxy-fullerenes have been found to protect cells specifically from H2O2 oxidative stress

 

Yin JJ, Lao F, Fu PP, Wamer WG, et al "The scavenging of reactive oxygen species and the potential for cell protection by functionalized fullerene materials" Biomaterials 30 (2009) pp 611-621

 

 

 

Furthermore, I can attest that some of my hair is starting to return to the color I had decades ago -- head hair, eyebrows and beard.

 

To be clear

 

1. not all grey hair is gone, some stragglers remain

2. the change to more vibrant color of youth rather than dull of middle age is in some places

 

I am trying to find some older pictures that show beard color and hair color when I was younger. Most are pre-digital low res and I didn't keep a beard regularly.

 

If it does cause H2O2 -- it must also cause a massive upregulation in catalase -- as catalase reveses grey hair -- from the link above

 

"The researchers found that this massive build up of hydrogen peroxide can be reversed with a UVB-activated compound called PC-KUS, a modified pseudocatalase"

 

 

Really nice study, and this C60+OO just keeps getting more and more amazing.   Having acknowledged that, I think you are putting the wrong spin on this.     C60 might simply be able to perform two different antioxidant functions, maybe by separate mechanisms.   In other words, C60 may behave as an SOD mimic and convert superoxide radical to H2O2.  C60 may then - separately in its role as a catalase mimic - neutralize the H2O2 to water and oxygen.

 

If your study is correct, and C60+OO is a mimic for both SOD and catalase, then in fact it would create more H2O2, and you simply don't see any effect from that because it also neutralizes the H2O2 it creates.

 

Does anyone know if there is a metabolite or test commonly available that would let us measure H2O2 levels in the tissues?   There are lipid peroxide tests available, but I'm not clear on how well any of those track H2O2 activity?  

 

I'm thinking that the users on Longecity need to propose a formal set of metabolites to track - before and after - using C60.   There is obviously something important going on here, and it must be measurable by metabolites.  It must be something we can quantify.   Home based photos of beard colors are nice but not as authoritative as what I think we could get by metabolites.

 

For example, we could use as metabolites:

 

* SOD levels

* Lipid Peroxides (but which specific markers)

 

Anything else?

[pone11]

Just wondering, what is the chance of C60 being a catalyst also being able to break down H2O2? It should be easy enough to test for anyone with C60 and some H2O2 from the pharmacy.

 

When I was younger I had lots of fun with H2O2 and Mn02. Unfortunately I don't have C60 yet, otherwise I would test it myself.

 

Hell of a good point....    Any chemists here want to do some experiments with C60 and H2O2?    How do we instrument that experiment and what are we measuring before and after?

[Nuke]

 

Just wondering, what is the chance of C60 being a catalyst also being able to break down H2O2? It should be easy enough to test for anyone with C60 and some H2O2 from the pharmacy.

 

When I was younger I had lots of fun with H2O2 and Mn02. Unfortunately I don't have C60 yet, otherwise I would test it myself.

 

Hell of a good point....    Any chemists here want to do some experiments with C60 and H2O2?    How do we instrument that experiment and what are we measuring before and after?

 

In my experience, when 35% H2O2 breaks down with Mn02 as catalyst, it will bubble alot and because the reaction is pretty exothermic it will speed up, in the end the H2O2 will boil. If C60 is a good catalyst, you should see a pretty vicious reaction. 

 

Not sure how the C60 as a powder will work with H202, my guess it that C60 is hydrophobic. Maybe dissolve the C60 in chlorobenzene first? Chlorobenzene at least have some solubility in water. 

 

Even if we find that it acts as catalyst in vitro, we still wont know if it does anything in the body though.

[pone11]

I have a theory on one of the ways in which C60oo may be working:

ROS damages DNA.

PARP is instrumental in DNA repair.

PARP requires NAD+.

As the amount of ROS increase; the amount of NAD+ required by PARP increases, leaving less for SIRT etc. and its longevity effects.

 

ie: C60oo cuts the amount of ROS; leading to less DNA damage; leading to less need for PARP; leading to an increase in available NAD+ available for SIRTs etc; leading to the lifespan increase seen in Baati's experiment.

 

Thoughts?

 

I am not going to pass judgement on the specific mechanism, but I am going to invoke Occam's Razor and ask why do we need this theory to accomplish anything useful?

 

To me, the basic problem is clear as night and day.  Denham Hardam originally proposed the free radical theory of aging, and in recent years that has been focused to the mitochondrial ROS theory of aging.   Mitochondria do a poor job of fixing damage to their DNA, so they are particularly susceptible to the effects of ROS.     What's critical to realize is that aerobic metabolism and electron transport chain (ETC) reside on the inner mitochondrial membrane.   So the mitochondria are in fact the source of most of the ROS - as a byproduct of the use of oxygen within the complexes of the ETC - and those delicate inner membranes are the ones that are then subjected to the effects of ROS most directly.   

 

The most basic ROS reaction is the production of superoxide radical in aerobic metabolism.   Superoxide is converted to hydrogen peroxide (H2O2) by SOD.   H2O2 is then converted to water and O2 by catalase.    In fighting mitochondrial aging, it is key to find a way to neutralize those superoxide radicals - in the mitochondria where they are being formed! - and transform them into something harmless.    

 

When we are young, our endogenous levels of SOD and catalase are sufficiently high to prevent serious damage to mitochondria.  When we are old, or sick, or have some mitochondrial disease, the levels of SOD and catalase fall - or the levels of ROS rise above what endogenous SOD and catalase can handle - and the mitochondria accumulate damage from ROS.

 

The papers quoted earlier in this subthread propose that C60+OO might act as an SOD mimic, and the second paper proposes some additional mechanism by which it performs a job similar to catalase.   This all fits in beautifully with our understanding of ROS in mitochondria.   It suggests very very clearly how C60+OO acts functionally to extend life, by preventing damage to mitochondria from ROS.  

 

Given that disclosure, why do we need your more complex theory with PARP and NAD+?   What does it help us accomplish?

Edited by pone11, 12 February 2015 - 09:28 PM.

[sensei]

 

 

Regarding H2O2, it is benign until it forms radical species.  These radicals can chain propagate and wreak all manner of havoc.  Catalase will safely dispatch peroxide, but maybe c60 is taking care of the problem after radical formation, by interrupting chain propagation.  This might explain how c60 could be having an effect on hair graying, despite the hypothetical possibility that it increases peroxide. 

 

 

http://www.howard.ed...g fullerene.pdf

 

According to this study fullerenes scavenge all physiologically relevant ROS -- and the downstream anions and radicals fromed from H2O2 decomposition

 

"Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O2 ), singlet oxygen, and hydroxyl radical (HO ), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities support the hypothesis that both chemical properties, such as surface chemistry induced differences in electron affinity, and physical properties, such as degree of aggregation, influence the biological and biomedical activities of functionalized fullerenes. This represents the first report that different types of fullerene derivatives can scavenge all physiologically relevant ROS. "

[pone11]

 

 

 

Regarding H2O2, it is benign until it forms radical species.  These radicals can chain propagate and wreak all manner of havoc.  Catalase will safely dispatch peroxide, but maybe c60 is taking care of the problem after radical formation, by interrupting chain propagation.  This might explain how c60 could be having an effect on hair graying, despite the hypothetical possibility that it increases peroxide. 

 

 

http://www.howard.ed...g fullerene.pdf

 

According to this study fullerenes scavenge all physiologically relevant ROS -- and the downstream anions and radicals fromed from H2O2 decomposition

 

"Consistent with their cytoprotective abilities, these derivatives can scavenge the stable 2,2-diphenyl-1-picryhydrazyl radical (DPPH), and the reactive oxygen species (ROS) superoxide radical anion (O2 ), singlet oxygen, and hydroxyl radical (HO ), and can also efficiently inhibit lipid peroxidation in vitro. The observed differences in free radical-scavenging capabilities support the hypothesis that both chemical properties, such as surface chemistry induced differences in electron affinity, and physical properties, such as degree of aggregation, influence the biological and biomedical activities of functionalized fullerenes. This represents the first report that different types of fullerene derivatives can scavenge all physiologically relevant ROS. "

 

 

C60 certainly appears to be a fantastic antioxidant.   Do we know for sure that it doesn't also intercept desirable metabolites like metals, enzymes, peptides in the cellular environments where it lands?  Has any study actually looked at what gets trapped inside the nanotubes that C60 forms to see what kind of cellular debris ends up there?    I'm not advancing any specific hypothesis, but I am asking what I think is a very relevant safety question:  does C60 remove anything that is "good" for us in addition to removing things (e.g., ROS) that are "bad"?

 

A related question is would the electrical charges on C60 be attractive to a heavy metal like mercury?  Would C60 have any role in a detox protocol, assuming that the trapped metal could then slip out of the cell encapsulated in a fullerene tube?    It would certainly be a fascinating experiment in vitro to see what happens when you mix mercury into solution with fullerenes.   It would be even more interesting to see what happens if you do that inside a cell membrane.  Does the trapped material get back out of the cell?

 

Can someone quote relevant studies on this issue?   Should be easy to test this in vitro....

Edited by pone11, 12 February 2015 - 11:00 PM.

[sensei]

 

Has any study actually looked at what gets trapped inside the nanotubes that C60 forms to see what kind of cellular debris ends up there?    

 

I'm not aware that C60 forms nanotubes. As far as I'm aware -- it takes alot of energy to open a buckyball.  AFAIK, most things form inclusion compounds (they surround the C60 molecule), or simply attach to the outside, like poly-hydroxylated C60.

[niner]

When we are young, our endogenous levels of SOD and catalase are sufficiently high to prevent serious damage to mitochondria.  When we are old, or sick, or have some mitochondrial disease, the levels of SOD and catalase fall - or the levels of ROS rise above what endogenous SOD and catalase can handle - and the mitochondria accumulate damage from ROS.

 

The papers quoted earlier in this subthread propose that C60+OO might act as an SOD mimic, and the second paper proposes some additional mechanism by which it performs a job similar to catalase.   This all fits in beautifully with our understanding of ROS in mitochondria.   It suggests very very clearly how C60+OO acts functionally to extend life, by preventing damage to mitochondria from ROS. 

 

 

Do we know that endogenous levels of SOD and catalase are high enough to preclude significant damage when we're young?   I'd expect that the level of protection is reasonable, but not enough to protect us any more that "needed" in youth, which is probably similar to the level of protection in early adulthood.

 

Which paper suggests that c60 acts like catalase?  I'm not sure which one you're talking about there, and don't recall seeing it.

[niner]

 

 

Has any study actually looked at what gets trapped inside the nanotubes that C60 forms to see what kind of cellular debris ends up there?    

 

I'm not aware that C60 forms nanotubes. As far as I'm aware -- it takes alot of energy to open a buckyball.  AFAIK, most things form inclusion compounds (they surround the C60 molecule), or simply attach to the outside, like poly-hydroxylated C60.

 

Sensei's right; it's really hard to get things into c60.  You have to synthesize the c60 around the atom you want to enclose, and one atom is about all there's room for.  C60 does not act as a shuttle, either into or out of the cell.  C60 also doesn't form nanotubes, at least not at biological temperatures.