635 replies to this topic

[niner]

Yesterday when i was pondering what i read about the immediate effects of c60 (what other people reported and a bit of my own experience), an idea struck me. Could it be that C60 directly affects red blood cells? I read that people taking c60 and donating blood reported unusual red blood color. More oxigenated blood cells could maybe explain the endurance effect a lot of people report (including me).

 

Since my medical knowledge is not very deep, i am posting this for the experts here to discuss or refute. Thanx for reading.

 

I'm not sure why someone rated this post "pointless, timewasting".  It's more clueful than a lot of the stuff we have to wade through.  I'm aware of the report of bright red venous blood, but a lot of other people using c60 have had blood draws and no one else has seen it.  I'm inclined to view it as a "red herring", as it were.   However, there are multiple ways that a compound could alter the oxygen carrying capacity of blood, so I think the basic idea is sound.  C60 might, for example, be acting through either a receptor-mediated or radical-related process to increase the hemoglobin content of red cells or to increase the number of red cells.  Our initial hypotheses regarding improved OXPHOS efficiency still make sense, but as of yet we lack experimental evidence for them.  As such, we shouldn't be too quick to ignore alternative explanations for the endurance effect.

[niner]

That was interesting Metrodorus. The kind of work that I hope gets attention by the medical community. Trying this substance on people whose life are in danger might be easier for an ethical board to recognize. Is there anything we can do to make the medical community aware of this?

 

What exactly do they mean by C60FAS? If I'm reading it right it's not terribly different from lipofullerenes. IV seemed to be the most effective, but I guess we can afford to stay away from that.

 

Yes, very interesting paper.  I'm not sure if the muscle fatigue processes are the same with and without IR injury, but they might be.  At any rate, C60FAS clearly shows it.  They describe C60FAS in the paper- it's a colloidal dispersion of pristine c60 in water.  This is Andrievsky's HyFn (Hydrated Fullerene).  If I have the story straight, it was discovered by Andrievsky.  He posts here occasionally.

 

This part in the discussion section talks about some possible ways that free radicals could cause damage in IR injury, and these things could be expected to occur at a much lower level simply from the radicals produced in the course of respiration.  The inhibition of the mitochondrial respiratory chain enzymes, in particular, might be a candidate explanation for the enhanced endurance people notice.  If the respiratory chain suffers from a chronic deficiency due to radical-induced inhibition of its components, then reducing that chronic problem should enhance OxPhos efficiency.

 

 

At the same time, the data available from literature indicate that free radicals (e. g., superoxide anion and hydroxyl groups) represent a major pathogenic factor in the process of ischemia-reperfusion tissue damage. It includes the initiation of lipid peroxidation, the direct inhibition of mitochondrial respiratory chain enzymes, inactivation of the glyceraldehyde 3-phosphate dehydrogenase, inhibiting ATP-ase activity, the inactivation of membrane sodium channels, etc. [38].   Superoxide anion radical is produced after ischemia at the stage of reperfusion in much larger quantities and quickly reacts with NO [39]. The ascorbic acid, which is a recognized antioxidant, was shown to have a positive effect on the reduction of muscle injury caused by ischemia-reperfusion [28]. It is assumed that the modified C60 fullerene may be regarded as a potent scavenger of free radicals induced by ischemia-reperfusion small intestine injury [19]. The feasibility of C60 fullerene derivatives to reduce ischemia-reperfusion lung injury has also been shown [18, 40]. In this regard, the protective effect of С60FAS on the fatigue processes in ischemically damaged muscle can be directly linked to the strong antioxidant properties of the pristine C60 fullerene [17].

[Kalliste]

I thought it was related but Andrievsky never mentioned the term "colloid" so I was unsure. I was glad to see that part you mentioned. That part and so many other little tidbits all adds up to c60 being an effective mitochondrial player, without dangerous side-effects that we know of so far. The injury-model they used is pretty dramatic, but I'm sure the same phenomenon plays out in smaller ways all the time. I hope someone in ER-circles notice that paper and tries it out, could be a boon for people who suffer traumatic injury.

[Adaptogen]

http://link.springer...4/fulltext.html

 

C₆₀ Fullerene as Synergistic Agent in Tumor-Inhibitory Doxorubicin Treatment

Objective

The aim of this study was to estimate the antitumor effect and antioxidant enzyme activity of combined C₆₀ fullerene and Dox (C₆₀ + Dox) in the liver and heart of mice with Lewis lung carcinoma compared with Dox treatment alone.

 

Methods

Highly stable pristine C₆₀ fullerene aqueous colloid solution (concentration 1.0 mg/ml, average hydrodynamic diameter of nanoparticles 50 nm) was used in the study and characterized by means of atomic force microscopy (AFM). The in vivo investigation of C₆₀-Dox action was performed via the standard methods of histological and enzyme activity analyses.

 

Results

Dox (total dose 2.5 mg/kg) combined with C₆₀ fullerene (total dose 25 mg/kg) in tumor-bearing animals resulted in tumor growth inhibition, prolongation of life, metastasis inhibition, and increased number of apoptotic tumor cells and was more effective than the corresponding course of Dox treatment alone. C₆₀ fullerene demonstrated a protective effect against superoxide dismutase and glutathione peroxidase inhibition induced by Dox-dependent oxidative insult in the liver and heart.

 

Conclusion

Combined treatment with C₆₀ + Dox is considered to be a promising approach for cancer chemotherapy.

 

Edited by Adaptogen, 13 December 2014 - 11:16 AM.

[Kalliste]

Good to see that Ukraine is not all war and misery. That goes nice in line with this, that I have posted in the past.

 

 

 

Yet in their Cell Reports paper, the researchers identified protein tyrosine kinases Src and Pyk2, affecting mitochondria that overload the electron transport chain, leading to superoxide production. Learning that, they used a common research antioxidant, mitoTEMPO, to "scavenge" the mitochondrial superoxide and discovered that doing so blocked tumor cell migration and prevented spontaneous tumor metastasis in mouse and human tumor models.

 

http://www.science20..._horizon-142136

[Turnbuckle]

 

http://link.springer...4/fulltext.html

 

 average hydrodynamic diameter of nanoparticles 50 nm

 

 

 

This would be a particle with several hundred molecules of C60.

[HighDesertWizard]

Should have posted this here...

 

 

Thinking out loud here about a C60-OO Common Anecdotal Effects Explanation focused on Catalase and H2O2... A few studies...

 

Gray Hair Reduction

• Premature Graying as a Consequence of Compromised Antioxidant Activity in Hair Bulb Melanocytes and Their Precursor

Increased Alcohol Tolerance

• Reduction in Central H2O2 Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2 System in Alcohol Binge Drinking

Reduced Skin Wrinkling

• H2O2 Accumulation by Catalase Reduction Changes MAP Kinase Signaling in Aged Human Skin In Vivo

And there's this, with implications for dosage regimen?

• Bioaccumulation of fullerene (C60) and corresponding catalase elevation in Lumbriculus variegatus

 

 

 

[sensei]

 

 

http://link.springer...4/fulltext.html

 

 average hydrodynamic diameter of nanoparticles 50 nm

 

 

 

This would be a particle with several hundred molecules of C60.

 

 

at .7nm diameter for C60,     http://web.mit.edu/a...on-JBH-2004.pdf

 

and a spherical diameter of 50nm for the aggregate particle

 

using 4/3*pi*(d/2)^3 for volume 

 

we get .17959 cubic nm for 1 C60 atom (4/3* pi* .35*.35*.35 cubic nm)

 

we get 65,449 cubic nm volume of the aggregate nano particle (4/3*pi*25*25*25 cubic nm)

 

unless my math is wrong there would be several hundred THOUSAND molecules of C60 in that aggregate

[Turnbuckle]

 

 

 

http://link.springer...4/fulltext.html

 

 average hydrodynamic diameter of nanoparticles 50 nm

 

 

 

This would be a particle with several hundred molecules of C60.

 

 

at .7nm diameter for C60,     http://web.mit.edu/a...on-JBH-2004.pdf

 

and a spherical diameter of 50nm for the aggregate particle

 

using 4/3*pi*(d/2)^3 for volume 

 

we get .17959 cubic nm for 1 C60 atom (4/3* pi* .35*.35*.35 cubic nm)

 

we get 65,449 cubic nm volume of the aggregate nano particle (4/3*pi*25*25*25 cubic nm)

 

unless my math is wrong there would be several hundred THOUSAND molecules of C60 in that aggregate

 

 

Yes, you are right. I pushed the wrong button on my calculator. But in any case, particles of 50 nm would not behave anything like dissolved particles with adducts derived from olive oil. 

[Kalliste]

I found a study that is semi-relevant to c60. If c60 is a mitochondrial antioxidant this should be an important part of the positive effects.

 

 

 

Enterovirus 71 Induces Mitochondrial Reactive Oxygen Species Generation That is Required for Efficient Replication

Redox homeostasis is an important host factor determining the outcome of infectious disease. Enterovirus 71 (EV71) infection has become an important endemic disease in Southeast Asia and China. We have previously shown that oxidative stress promotes viral replication, and progeny virus induces oxidative stress in host cells. The detailed mechanism for reactive oxygen species (ROS) generation in infected cells remains elusive. In the current study, we demonstrate that mitochondria were a major ROS source in EV71-infected cells. Mitochondria in productively infected cells underwent morphologic changes and exhibited functional anomalies, such as a decrease in mitochondrial electrochemical potential ΔΨ_m and an increase in oligomycin-insensitive oxygen consumption. Respiratory control ratio of mitochondria from infected cells was significantly lower than that of normal cells. The total adenine nucleotide pool and ATP content of EV71-infected cells significantly diminished. However, there appeared to be a compensatory increase in mitochondrial mass. Treatment with mito-TEMPO reduced eIF2α phosphorylation and viral replication, suggesting that mitochondrial ROS act to promote viral replication. It is plausible that EV71 infection induces mitochondrial ROS generation, which is essential to viral replication, at the sacrifice of efficient energy production, and that infected cells up-regulate biogenesis of mitochondria to compensate for their functional defect.

http://www.plosone.o...al.pone.0113234

Edited by Cosmicalstorm, 18 December 2014 - 10:07 AM.

[Sholrak]

 

Yesterday when i was pondering what i read about the immediate effects of c60 (what other people reported and a bit of my own experience), an idea struck me. Could it be that C60 directly affects red blood cells? I read that people taking c60 and donating blood reported unusual red blood color. More oxigenated blood cells could maybe explain the endurance effect a lot of people report (including me).

 

Since my medical knowledge is not very deep, i am posting this for the experts here to discuss or refute. Thanx for reading.

 

I'm not sure why someone rated this post "pointless, timewasting".  It's more clueful than a lot of the stuff we have to wade through.  I'm aware of the report of bright red venous blood, but a lot of other people using c60 have had blood draws and no one else has seen it.  I'm inclined to view it as a "red herring", as it were.   However, there are multiple ways that a compound could alter the oxygen carrying capacity of blood, so I think the basic idea is sound.  C60 might, for example, be acting through either a receptor-mediated or radical-related process to increase the hemoglobin content of red cells or to increase the number of red cells.  Our initial hypotheses regarding improved OXPHOS efficiency still make sense, but as of yet we lack experimental evidence for them.  As such, we shouldn't be too quick to ignore alternative explanations for the endurance effect.

 

 

 

 

Respect to the scarlet red color blood, I think we all knew it already, I found this: http://www.ncbi.nlm....pubmed/22845854

 

In fact, that comments of that woman donating blood catched greatly my attention towards c60.

 

 

Abstract

Blood color of dialysis patients can be seen routinely. Darkened blood color is often observed in critically ill patients generally because of decreased oxygen saturation, but little is known about the other factors responsible for the color intensity. In addition, quantitative blood color examination has not been performed yet. Therefore, no one has evaluated the predictive power of blood color. The aim of this study was to evaluate if blood color darkness reflects some medical problems and is associated with survival disadvantage. Study design is a prospective cohort study. One hundred sixty-seven patients were enrolled in this study. Quantification of blood color was done using a reflected light colorimeter. Demographic and clinical data were collected to find out the factors that can be related to blood color. Follow-ups were performed for 2 years to analyze the risk factors for their survival. Regression analysis showed that C-reactive protein and white blood cell count were negatively correlated with blood color. In addition, blood color was positively correlated with mean corpuscular hemoglobin concentration and serum sodium concentration as well as blood oxygen saturation. During a follow-up, 34 (20.4%) patients died. Cox regression analysis revealed that darkened blood color was an independent significant risk factor of mortality in hemodialysis patients as well as low albumin and low Kt/V. These results suggest that inflammation independently affects blood color and quantification of blood color is useful to estimate prognosis in patients undergoing hemodialysis. It is possible that early detection of blood color worsening can improve patients' survival.

© 2012, Copyright the Authors. Artificial Organs © 2012, International Center for Artificial Organs and Transplantation and Wiley Periodicals, Inc.

 

Edited by Sholrak, 20 December 2014 - 04:55 PM.

[pone11]

I am completely new to this C60 research on mice, which on the face is pretty exciting stuff!    The one thing I pick up on right away that seems quite weird is that the mice fed just olive oil also lived almost twice as long.   The C60 plus olive oil had the best result, but the most dramatic difference was between the control group and the group fed just olive oil.  The incremental extension from C60+olive oil was not huge.   (I do realize the mice in that group might have lived longer if the experiment had continued.)

 

Has anyone come up with good ideas on why the mice fed just olive oil lived so long?

[Turnbuckle]

I am completely new to this C60 research on mice, which on the face is pretty exciting stuff!    The one thing I pick up on right away that seems quite weird is that the mice fed just olive oil also lived almost twice as long.   The C60 plus olive oil had the best result, but the most dramatic difference was between the control group and the group fed just olive oil.  The incremental extension from C60+olive oil was not huge.   (I do realize the mice in that group might have lived longer if the experiment had continued.)

 

Has anyone come up with good ideas on why the mice fed just olive oil lived so long?

 

You should read the actual paper, which says--

 

The survival distributions for C60-olive oil-treated rats and

controls were estimated by the non-parametric KaplaneMeier

estimator (Fig. 3) and compared by a log-rank estimated test. The

estimated median lifespan (EML) for the C60-treated rats was 42

months while the EMLs for control rats and olive oil-treated rats

were 22 and 26 months, respectively. These are increases of 18 and

90% for the olive-oil and C60-treated rats, respectively, as compared

to controls.

 

http://extremelongev...0-Fullerene.pdf

 

 

 

[Turnbuckle]

 

 

All clear now thanks and yes an impressive result.  I hope it is duplicated.

 

 

The results for olive oil are still impressive. So not surprising that the oldest woman in the world claimed that olive oil was the secret to long life, at least in part. She finally died at 121--

 

Calment ascribed her longevity and relatively youthful appearance for her age to a diet rich in olive oil (which she also rubbed onto her skin), as well as a diet of port wine, and ate nearly one kilogram of chocolate every week. 

 

http://en.wikipedia..../Jeanne_Calment

 

 

 

She died 2 years after a doctor convinced her to improve her diet.

[HighDesertWizard]

C60-OO Common Anecdotal Effects and Catalase Expression...

Thinking out loud here about a C60-OO Common Anecdotal Effects Explanation focused on Catalase and H2O2... A few studies...
 
Gray Hair Reduction

• Premature Graying as a Consequence of Compromised Antioxidant Activity in Hair Bulb Melanocytes and Their Precursor

Increased Alcohol Tolerance

• Reduction in Central H2O2 Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2 System in Alcohol Binge Drinking

Reduced Skin Wrinkling

• H2O2 Accumulation by Catalase Reduction Changes MAP Kinase Signaling in Aged Human Skin In Vivo

And there's this, with implications for dosage regimen?

• Bioaccumulation of fullerene (C60) and corresponding catalase elevation in Lumbriculus variegatus

 

A question... Do the anecdotal effects of C60-OO ingestion related to Gray Hair, Alcohol Tolerance, and Reduced Skin Wrinkling take place through a mechanism involving increased Catalase Expression? Or not?

 

If Not, isn't the implication this? That there is a mechanism for catalase expression impacting Gray Hair, Increased Alcohol Tolerance, and Reduced Skin Wrinkling and a mechanism that does Not involve Catalase? Two different mechanisms? What sense does that make? 

 

Is there a reason not to make the simple assumption that C60-OO increases catalase expression?

 

Catalase and Telomerase

 

The idea that increased Telomerase expression had anything to do with the benefits to life span for the Baati study C60-OO rats has been dismissed. Still, there are those scientific reference links about catalase and the question they raise noted above. And then there is this...

 

Telomerase deficiency promotes oxidative stress by reducing catalase activity

 

An implication? Increased Telomerase expression reduces oxidative stress by increasing catalase activity?

 

Isagenix Product B and Catalase

 

In a time of accelerating increases in knowledge, when published research doesn't keep pace with research done, it's useful to understand where the work of significant figures in the LE movement (like Bill Andrews) is going, published or not.

 

Isagenix Announces New Findings on Product B

 

At the end of the study, the subjects using Product B showed a significant elevation of catalase in subjects’ red blood cells. Compared to those who took the placebo, the subjects on Product B had increased their catalase activity by more than 30 percent. The findings suggest profound benefits attributed to Product B supplementation.

 

The relevance of this finding was not lost on the researchers, who commented, “The increase in catalase observed by Product B is an exciting development considering the relationship between the enzyme and increased lifespan in animal studies."

 

Now that the study is completed, it’s expected to be submitted for publication in a peer-reviewed journal in 2015.

 

Thoughts?

Edited by HighDesertWizard, 25 December 2014 - 10:01 PM.

[sensei]

Of interest is that in the presence of (high?) levels of ROS, telomerase migrates from the nucleus to the mitochondria to help.

 

http://www.anti-agin...ase-activators/

 

http://jcs.biologist...121/7/1046.full

 

"

Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress"

 

 

So, if high levels of oxidative stress cause telomerase to be used for combating ROS to protect mitochondria 

 

Is it a baseless assumption to posit that the presence of C60OO in/near the mitochondria reducing ROS, allows the naturally occurring telomerase in the nucleus to stay put and lengthen telomeres or protect nuclear DNA like it should?

Edited by sensei, 25 December 2014 - 09:57 PM.

[niner]

C60-OO Common Anecdotal Effects and Catalase Expression...

Thinking out loud here about a C60-OO Common Anecdotal Effects Explanation focused on Catalase and H2O2... A few studies...
 
Gray Hair Reduction

• Premature Graying as a Consequence of Compromised Antioxidant Activity in Hair Bulb Melanocytes and Their Precursor

Increased Alcohol Tolerance

• Reduction in Central H2O2 Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2 System in Alcohol Binge Drinking

Reduced Skin Wrinkling

• H2O2 Accumulation by Catalase Reduction Changes MAP Kinase Signaling in Aged Human Skin In Vivo

And there's this, with implications for dosage regimen?

• Bioaccumulation of fullerene (C60) and corresponding catalase elevation in Lumbriculus variegatus

 

A question... Do the anecdotal effects of C60-OO ingestion related to Gray Hair, Alcohol Tolerance, and Reduced Skin Wrinkling take place through a mechanism involving increased Catalase Expression? Or not?

 

If Not, isn't the implication this? That there is a mechanism for catalase expression impacting Gray Hair, Increased Alcohol Tolerance, and Reduced Skin Wrinkling and a mechanism that does Not involve Catalase? Two different mechanisms? What sense does that make? 

 

Is there a reason not to make the simple assumption that C60-OO increases catalase expression?

 

The grey hair effect might be an antioxidant effect, but it wouldn't necessarily have anything to do with catalase expression levels.  If c60oo suppresses superoxide levels, then there will be less H2O2, which would look the same as catalase upregulation.

 

The effect in the mice goes in the wrong direction, in that the antioxidants caused mice to drink less.  Some of us are probably drinking more rather than less, because we're missing the usual alcohol cues.  I think this is probably a receptor-mediated rather than an antioxidant effect.

 

Catalase activity was reduced in photoaged skin, which might be one of the things that leads to wrinkling.  It's plausible that an exogenous antioxidant could make up for this problem, if it was in place over a long (years) period.  If there is a rapid change in skin wrinkling from c60, meaning that long-damaged tissue had been repaired in some way, then I think something else is going on.  Stem cell related, perhaps?

 

The bioaccumulation paper used large aggregates, and they are very different from c60oo, which is a molecular species.  Aggregates of c60 can be pro-oxidant, rather than anti.  That might raise catalase by a hormetic effect.

[niner]

Of interest is that in the presence of (high?) levels of ROS, telomerase migrates from the nucleus to the mitochondria to help.

 

http://www.anti-agin...ase-activators/

 

http://jcs.biologist...121/7/1046.full

 

"Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress"

 

So, if high levels of oxidative stress cause telomerase to be used for combating ROS to protect mitochondria 

 

Is it a baseless assumption to posit that the presence of C60OO in/near the mitochondria reducing ROS, allows the naturally occurring telomerase in the nucleus to stay put and lengthen telomeres or protect nuclear DNA like it should?

 

I don't think that's baseless.  We know that oxidative stress causes telomere shortening, and TERT getting sidetracked into protecting the mitochondria may well have something to do with it.  (Another possible reason is that oxidative damage to telomeric DNA isn't repaired as well as it would be in coding DNA.)  So yeah, if you effectively knock down oxidative stress, you might preserve telomeres through either of these mechanisms, or both.

[sensei]

 

Of interest is that in the presence of (high?) levels of ROS, telomerase migrates from the nucleus to the mitochondria to help.

 

http://www.anti-agin...ase-activators/

 

http://jcs.biologist...121/7/1046.full

 

"Telomerase does not counteract telomere shortening but protects mitochondrial function under oxidative stress"

 

So, if high levels of oxidative stress cause telomerase to be used for combating ROS to protect mitochondria 

 

Is it a baseless assumption to posit that the presence of C60OO in/near the mitochondria reducing ROS, allows the naturally occurring telomerase in the nucleus to stay put and lengthen telomeres or protect nuclear DNA like it should?

 

I don't think that's baseless.  We know that oxidative stress causes telomere shortening, and TERT getting sidetracked into protecting the mitochondria may well have something to do with it.  (Another possible reason is that oxidative damage to telomeric DNA isn't repaired as well as it would be in coding DNA.)  So yeah, if you effectively knock down oxidative stress, you might preserve telomeres through either of these mechanisms, or both.

 

 

That is my theory regarding the Baati effect.

 

1. ROS reduction by C60OO effect on mitochondria increases mitochondrial turnover -- which has been directly linked to slower telomeric shortening

2. ROS reduction by C60OO effect on mitochondria decreases migration of TERT from the nucleus to the mitochondria, thereby allowing telomerase to repair nuclear DNA damage and also lengthen telomeres (both of which may arrest cellular senescence, or revert the cell to a younger state)

3. I believe there may also be some mechanism by which C60OO helps remove garbage from the cell as well.

[niner]

3. I believe there may also be some mechanism by which C60OO helps remove garbage from the cell as well.

 

Maybe by creating less of it in the first place.  One of the major garbage molecules is an oxidized form of cholesterol that lysosomal enzymes can't degrade.  It builds up over time until the lysosome gets large and dysfunctional.  Oxidized PUFAs are a major component of lipofuscin.  The formation of such forms of garbage might well be reduced by c60oo.  Unfortunately, it's unlikely that c60oo can do anything about garbage that has already accumulated.

[sensei]

 

3. I believe there may also be some mechanism by which C60OO helps remove garbage from the cell as well.

 

Maybe by creating less of it in the first place.  One of the major garbage molecules is an oxidized form of cholesterol that lysosomal enzymes can't degrade.  It builds up over time until the lysosome gets large and dysfunctional.  Oxidized PUFAs are a major component of lipofuscin.  The formation of such forms of garbage might well be reduced by c60oo.  Unfortunately, it's unlikely that c60oo can do anything about garbage that has already accumulated.

 

 

Unless they happen to have an affinity for the molecular structure of C60 -- and ride out with it when it leaves

[HighDesertWizard]

 

C60-OO Common Anecdotal Effects and Catalase Expression...

Thinking out loud here about a C60-OO Common Anecdotal Effects Explanation focused on Catalase and H2O2... A few studies...
 
Gray Hair Reduction

• Premature Graying as a Consequence of Compromised Antioxidant Activity in Hair Bulb Melanocytes and Their Precursor

Increased Alcohol Tolerance

• Reduction in Central H2O2 Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2 System in Alcohol Binge Drinking

Reduced Skin Wrinkling

• H2O2 Accumulation by Catalase Reduction Changes MAP Kinase Signaling in Aged Human Skin In Vivo

And there's this, with implications for dosage regimen?

• Bioaccumulation of fullerene (C60) and corresponding catalase elevation in Lumbriculus variegatus

 

A question... Do the anecdotal effects of C60-OO ingestion related to Gray Hair, Alcohol Tolerance, and Reduced Skin Wrinkling take place through a mechanism involving increased Catalase Expression? Or not?

 

If Not, isn't the implication this? That there is a mechanism for catalase expression impacting Gray Hair, Increased Alcohol Tolerance, and Reduced Skin Wrinkling and a mechanism that does Not involve Catalase? Two different mechanisms? What sense does that make? 

 

Is there a reason not to make the simple assumption that C60-OO increases catalase expression?

 

The grey hair effect might be an antioxidant effect, but it wouldn't necessarily have anything to do with catalase expression levels.  If c60oo suppresses superoxide levels, then there will be less H2O2, which would look the same as catalase upregulation.

 

The effect in the mice goes in the wrong direction, in that the antioxidants caused mice to drink less.  Some of us are probably drinking more rather than less, because we're missing the usual alcohol cues.  I think this is probably a receptor-mediated rather than an antioxidant effect.

 

Catalase activity was reduced in photoaged skin, which might be one of the things that leads to wrinkling.  It's plausible that an exogenous antioxidant could make up for this problem, if it was in place over a long (years) period.  If there is a rapid change in skin wrinkling from c60, meaning that long-damaged tissue had been repaired in some way, then I think something else is going on.  Stem cell related, perhaps?

 

The bioaccumulation paper used large aggregates, and they are very different from c60oo, which is a molecular species.  Aggregates of c60 can be pro-oxidant, rather than anti.  That might raise catalase by a hormetic effect.

 

 

My post above also contained the study below making specific reference to the relationship of telomerase to catalase. A single study does not a point prove but, it seems to me, ought to trigger more openness about a potential role for catalase rather than quick dismissal.

 

Telomerase deficiency promotes oxidative stress by reducing catalase activity

 

Telomere shortening and redox imbalance have been related to the aging process. We used cultured mouse embryonic fibroblasts (MEF) isolated from mice lacking telomerase activity (Terc−/−) to analyze the redox balance and the functional consequences promoted by telomerase deficiency. Comparison with wild-type (WT) MEF showed that Terc−/− MEF had greater oxidant damage, showing higher superoxide anion and hydrogen peroxide production and lower catalase activity. Restoration of telomerase activity in Terc−/− MEF increased catalase expression and activity. TGF-β1 and collagen type IV levels were higher in Terc−/− than in WT MEF. TGF-β1 promoter activity decreased when Terc−/− MEF were incubated with exogenous catalase, suggesting that catalase deficiency is the cause of the TGF-β1 increase. Similar results were obtained in vivo. Homogenized renal cortex from 6-month-old Terc−/− showed higher oxidant capacity, lower catalase activity, greater oxidative damage, and higher TGF-β1 and fibronectin levels than that from WT mice. In summary, telomerase deficiency reduces catalase activity, determining a redox imbalance that promotes overexpression of TGF-β1 and extracellular matrix proteins.

[pone11]

A question... Do the anecdotal effects of C60-OO ingestion related to Gray Hair, Alcohol Tolerance, and Reduced Skin Wrinkling take place through a mechanism involving increased Catalase Expression? Or not?

 

If Not, isn't the implication this? That there is a mechanism for catalase expression impacting Gray Hair, Increased Alcohol Tolerance, and Reduced Skin Wrinkling and a mechanism that does Not involve Catalase? Two different mechanisms? What sense does that make? 

 

Is there a reason not to make the simple assumption that C60-OO increases catalase expression?

 

 

Just to enumerate more of the possible mechanisms that might be at play:

 

* C60+OO could be increasing superoxide dismutase (SOD) or catalase levels, possibly through genetic changes

 

* C60+OO could be somehow increasing the bioavailability of endogenous SOD or catalase levels, possibly through genetic changes

 

* C60+OO could be preventing the superoxide radical from forming, thereby making endogenous catalase levels more effective

 

* C60+OO could be a totally novel and self-sufficient antioxidant, effectively replacing the role of SOD and/or catalase

 

I could go on....   But the freakish thing is that C60 is short lived and was only dosed weekly in the Baati study.   That tends to argue for it making changes that affect endogenous systems, possibly genetic changes.     I hope one of the new studies tries to give C60 for a short time and then just stops it cold turkey.   Won't it be interesting if those rats also live a long time, due to some sustained genetic manipulation.

Edited by pone11, 27 December 2014 - 11:47 PM.

[Kalliste]

Did not see this posted in this forum. It will be interesting to see. Kudos to the Ukrainians for keeping at it in the face of war. Lets hope the war does not expand.

 

 

4) Ongoing C60 experiments

After many difficulties in setting the experiment (cross-border transportation in current geopolitical times, checking absorption in mice/ detecting C60/correct source of C60, administration tried in food and replaced by gavage, training for gavage and various measures) we have transposed the popular lifespan test with c60 fullerenes reported in rats by Baati et al. to mice (CBA strain, common in the lab) and with more animals (N=17 per group). There are three groups (gavage of water, of olive oil, of C60 dissolved in olive oil), there are ... a lot of health measures and a lot of gavage (at the beginnings of the experiment as administrations are first very frequent and then gradually less frequent). Given that the experiment starts with mid-aged animals, the results are expected for the beginning of 2016.

The original C60 results from a few years back were greeted with some skepticism in the research community, given the very large size of the effect claimed and the small number of animals tested. There was, I think, also a certain annoyance: now that someone had made what was on the face of it an unlikely claim of significant life span extension via administration of C60, then some other group was going to have to waste their time in disproving it. We'll see how that all turns out, I suppose. This is science as it works in practice.

At some point the broad structural classes of research illustrated by the Interventions Testing Program and this crowdfunded mouse study will meet in the middle, and the process of funding and organizing scientific programs will be a far more complicated, dynamic, and public affair than is presently the case. I think this will be for the better. All that we have we owe to science, and a majority of the public thinks all too little of the work that will determine whether they live in good health or suffer and die a few decades from now. The more they can see what is going on the better for all of us in the end, I think.

 

 

¨https://www.fightagi...-span-study.php

[niner]

 

 

C60-OO Common Anecdotal Effects and Catalase Expression...

Thinking out loud here about a C60-OO Common Anecdotal Effects Explanation focused on Catalase and H2O2... A few studies...
 
Gray Hair Reduction

• Premature Graying as a Consequence of Compromised Antioxidant Activity in Hair Bulb Melanocytes and Their Precursor

Increased Alcohol Tolerance

• Reduction in Central H2O2 Levels Prevents Voluntary Ethanol Intake in Mice: A Role for the Brain Catalase-H2O2 System in Alcohol Binge Drinking

Reduced Skin Wrinkling

• H2O2 Accumulation by Catalase Reduction Changes MAP Kinase Signaling in Aged Human Skin In Vivo

And there's this, with implications for dosage regimen?

• Bioaccumulation of fullerene (C60) and corresponding catalase elevation in Lumbriculus variegatus

 

A question... Do the anecdotal effects of C60-OO ingestion related to Gray Hair, Alcohol Tolerance, and Reduced Skin Wrinkling take place through a mechanism involving increased Catalase Expression? Or not?

 

If Not, isn't the implication this? That there is a mechanism for catalase expression impacting Gray Hair, Increased Alcohol Tolerance, and Reduced Skin Wrinkling and a mechanism that does Not involve Catalase? Two different mechanisms? What sense does that make? 

 

Is there a reason not to make the simple assumption that C60-OO increases catalase expression?

 

The grey hair effect might be an antioxidant effect, but it wouldn't necessarily have anything to do with catalase expression levels.  If c60oo suppresses superoxide levels, then there will be less H2O2, which would look the same as catalase upregulation.

 

The effect in the mice goes in the wrong direction, in that the antioxidants caused mice to drink less.  Some of us are probably drinking more rather than less, because we're missing the usual alcohol cues.  I think this is probably a receptor-mediated rather than an antioxidant effect.

 

Catalase activity was reduced in photoaged skin, which might be one of the things that leads to wrinkling.  It's plausible that an exogenous antioxidant could make up for this problem, if it was in place over a long (years) period.  If there is a rapid change in skin wrinkling from c60, meaning that long-damaged tissue had been repaired in some way, then I think something else is going on.  Stem cell related, perhaps?

 

The bioaccumulation paper used large aggregates, and they are very different from c60oo, which is a molecular species.  Aggregates of c60 can be pro-oxidant, rather than anti.  That might raise catalase by a hormetic effect.

 

 

My post above also contained the study below making specific reference to the relationship of telomerase to catalase. A single study does not a point prove but, it seems to me, ought to trigger more openness about a potential role for catalase rather than quick dismissal.

 

Telomerase deficiency promotes oxidative stress by reducing catalase activity

 

Telomere shortening and redox imbalance have been related to the aging process. We used cultured mouse embryonic fibroblasts (MEF) isolated from mice lacking telomerase activity (Terc−/−) to analyze the redox balance and the functional consequences promoted by telomerase deficiency. Comparison with wild-type (WT) MEF showed that Terc−/− MEF had greater oxidant damage, showing higher superoxide anion and hydrogen peroxide production and lower catalase activity. Restoration of telomerase activity in Terc−/− MEF increased catalase expression and activity. TGF-β1 and collagen type IV levels were higher in Terc−/− than in WT MEF. TGF-β1 promoter activity decreased when Terc−/− MEF were incubated with exogenous catalase, suggesting that catalase deficiency is the cause of the TGF-β1 increase. Similar results were obtained in vivo. Homogenized renal cortex from 6-month-old Terc−/− showed higher oxidant capacity, lower catalase activity, greater oxidative damage, and higher TGF-β1 and fibronectin levels than that from WT mice. In summary, telomerase deficiency reduces catalase activity, determining a redox imbalance that promotes overexpression of TGF-β1 and extracellular matrix proteins.

 

The question you asked was whether or not catalase was involved in the observed effects of c60oo.  I don't see what an artificial telomerase deficiency even has to do with this, which is why I didn't respond to it.  My response was not a "quick dismissal".   I looked at the papers you posted, and responded to your points.  You may not like the answer, but it wasn't quick.

[pone11]

Does anyone know what is the maximum lifespan of the breed of mouse used in the C60 study?   

 

Most studies only manage to improve average lifespan of a species, and they almost never alter the maximum lifespan.

[niner]

 But the freakish thing is that C60 is short lived and was only dosed weekly in the Baati study.   That tends to argue for it making changes that affect endogenous systems, possibly genetic changes.

 

Baati's report that c60oo was cleared from blood in a relatively short time has led to a lot of confusion.  In fact, Baati couldn't tell that c60 was leaving the rat, only that they were no longer seeing it in blood.  "Not seeing it" doesn't mean it's not there, it means that it's below the limit of detection.  What many of us think is going on is that the c60-fatty acid adduct is getting incorporated into membranes.  This could explain its disappearance from blood.  It's also clear from various reports in the literature as well as our own experiences with it that c60 is extremely potent, and is active at very low concentrations.  (Andrievsky has published on this at length.)  The combination of being located in membrane lipid depots, as well as being active at extremely low concentration makes it active for a very long time, due to very long half life in membranes and very low threshold concentration.  This could explain our observations without resorting to a genetic explanation for which a mechanism is lacking.

[pone11]

 

 But the freakish thing is that C60 is short lived and was only dosed weekly in the Baati study.   That tends to argue for it making changes that affect endogenous systems, possibly genetic changes.

 

Baati's report that c60oo was cleared from blood in a relatively short time has led to a lot of confusion.  In fact, Baati couldn't tell that c60 was leaving the rat, only that they were no longer seeing it in blood.  "Not seeing it" doesn't mean it's not there, it means that it's below the limit of detection.  What many of us think is going on is that the c60-fatty acid adduct is getting incorporated into membranes.  This could explain its disappearance from blood.  It's also clear from various reports in the literature as well as our own experiences with it that c60 is extremely potent, and is active at very low concentrations.  (Andrievsky has published on this at length.)  The combination of being located in membrane lipid depots, as well as being active at extremely low concentration makes it active for a very long time, due to very long half life in membranes and very low threshold concentration.  This could explain our observations without resorting to a genetic explanation for which a mechanism is lacking.

 

 

Can you tag the C60 with any kind of radioactivity, or are they too small for that?

 

There is no technology to count them from the collected urine?

 

To test your theory, couldn't they just try to evaluate the amount of C60 present in some individual tissue cells and RBC, and attempt to extrapolate from those samplings to the entire animal?

 

Your idea is interesting, and if true then given the half life of poly fats is about 600 days, that implies after three years you still have about 25% of the original dose in the cell membrane.   What would be the mechanism for extending life if they are in the membrane?

[Kalliste]

I am not sure how to interpret these results. Did the fullerenol molecule somehow inhibit the activity of E.Coli? That would not be too bad. The N-c60 did not seem to have that effect.

 

Fullerenes are exciting chemicals having great promise in biomedical applications. The toxicity of these nanoparticles on organism's metabolism remains a longstanding challenge in biomedical science. Toward this objective, we explored the interaction of two commonly used fullerene species, nano-C₆₀ and fullerenols, with bacterial cells and their impact on cell growth and metabolism using Escherichia coli under aerobic and anaerobic conditions. Results revealed that fullerenol interactions could promote cell growth and affect cellular metabolism significantly. Here we report potent inhibition of the ethanol generation caused by fullerenols. In comparison, nano-C₆₀ interaction can hardly affect ethanol production and other bacterial activities. Enzyme assay studies suggested that the inhibition of ethanol generation was not due to the gene regulation. These data implicated the application of fullerenols could have considerable impact on cell growth, and enzymatic and metabolic performance of Escherichia coli.

http://www.ingentaco...000007/art00014

 

[ambivalent]

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?

Edited by ambivalent, 14 January 2015 - 07:40 PM.