3585 replies to this topic

[Turnbuckle]

If we do believe it, then we should start drinking EVOO. (I like EVOO, but 4/5 of a cup doesn't seem very appealing.)

You can do it for a week or two, right?

[Junk Master]

What's the theory behind a week or two of 4/5 cup of EVOO producing a marked effect on longevity versus smaller amounts over a longer period of time?

[arska]

Aggregates are filtered out, so if the hypothesis were that the tyrosol is sneaking in by hiding inside a very small aggregate that managed to pass through the filter, I don't think there could be enough mass of C60 in that form to bring in enough tyrosol to matter.

Yes, this was the idea..some sort of aggregate like [http://www.sciencedi...254058411004767]
and as tyrosol is some sort of alcohol I was curious...

regards,

[Turnbuckle]

What's the theory behind a week or two of 4/5 cup of EVOO producing a marked effect on longevity versus smaller amounts over a longer period of time?

That's the rat trial, right? A week, then once a week for six months. Doesn't sound too hard. As for a theory, you have to once again look to epigenetics.

Virgin olive oil in preventive medicine: From legend to epigenetics

and from Gene expression changes in mononuclear cells in patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil--

CONCLUSION:

This study shows that intake of virgin olive oil based breakfast, which is rich in phenol compounds is able to repress in vivo expression of several pro-inflammatory genes, thereby switching activity of peripheral blood mononuclear cells to a less deleterious inflammatory profile. These results provide at least a partial molecular basis for reduced risk of cardiovascular disease observed in Mediterranean countries, where virgin olive oil represents a main source of dietary fat.

Edited by Turnbuckle, 18 June 2012 - 10:31 PM.

[Junk Master]

Not bad at all. I'm curious about the anti-inflammatory properties of such high doses. I have a decent aerobic base at the moment and would be able to accurately (subjectively, of course) judge any improvement in recovery time, delayed onset muscle soreness, and I think we can all agree there's no harm in drinking olive oil. Unless you injure yourself vomiting.

[maxwatt]

It helps to put the olive oil on your linguini and spaghetti, in your salad and to use it instead of butter on your artisan baked bread and your grilled salmon and grilled vegetables.. It's easy to get 4/5 of a cup a day get that way.

Some of us have been using high phenolic EVOO for a while, but we don't swig it.

[smithx]

I just want to highlight this point because I think it's important.

Cell membranes are critical for cell functioning, and their shape is of utmost importance. Generally, the proteins float at
specific heights in the membrane and also can move across the membrane. These heights and that movement are also critical. In fact, agents such as plant lectins, which crosslink the glycoproteins, often cause cell death due to clumping of membrane proteins.


If something is sitting between the lipid layers, as C60 is believed to do, that could be fine up to a point. But if there's too much of it, it could alter membrane configuration in a bad way by reducing mobility of proteins, glycolipids, etc. or by changing the heights or angles at which they float.



In that image, taken from the article http://pubs.rsc.org/...1/CC/c1cc14650e linked by Metrodorus, we can see that the C60 is pushing the phospholipids up out of the membrane plane, which is likely to cause reduced mobility and other issues. If the benefit provided by the C60 outweighs these issues, that's fine.

But it's easy to imagine that too much C60 in a membrane would start to gum up the works, as it were, and cause some serious problems.

Based on this, and all the other unknowns and potential risks. I really urge people to be careful with this stuff. If you're going to use it, just use small quantities and stop after a short time.

Turnbuckle's reference to Eben Byers, who found that radium water worked wonders for him and so kept on taking it until it killed him is right on point:

http://en.wikipedia....wiki/Eben_Byers

Experimental confirmation (2011) that fullerene is taken up and incorporated in cell membranes:
http://pubs.rsc.org/...1/CC/c1cc14650e

[Metrodorus]

I

I think this computer simulation is closer to reality.
http://pubs.rsc.org/...009/sm/b912310e


Computer simulations of the interaction of fullerene with lipid membranes

Collaborations: Emppu Salonen (TKK, Finland), Pu-Chun Ke (Clemson Univ., USA) and Ilpo Vattulainen (TUT, Finland)
Fullerenes are biologically active and can enter easily both plant and animal cells. Yet, it is not clear how these nanomaterials enter cells through cell membranes and what are the mechanisms of their biological activity. It has been shown that natural organic matter (NOM) interacts strongly with carbon nanoparticles and alters their interaction with cells. In particular, it has been shown that a mixture of fullerene and gallic acid – an important component of NOM – can cause cell membrane damage and cell death by unknown mechanisms. My goal is to employ computer simulations to understand the molecular interactions between fullerene and model membranes, both in the absence and in the presence of NOM, and to explore different possible mechanisms of cell membrane damage.

slightly off topic - this video on YouTube on mitochondria is pretty amazing -

Edited by Metrodorus, 19 June 2012 - 01:56 AM.

[NewtonPulsifer]

...snip...
That said, I believe the "Cell-Membrane-ROS-Scavenging-As-Essential Mechanism-Explanation" folks should have have a backup hypothesis. The longer term life span enhancing effects experienced by the Baati rats have to be explained somehow. Earlier up thread, niner had tied these effects specifically to the C60 extended stay in the membrane hypothesis.
...snip...

I have to disagree; it is enough.

Pigeons have a 5-fold higher maximum lifespan than rats (35 vs. 7 years) with a similar weight and metabolic rate. Birds have vastly superior lungs and mitochondria compared to mammals, and live far longer.

Improved mitochondria function alone is enough.

http://en.wikipedia....ximum_life_span

[niner]

In that image, taken from the article http://pubs.rsc.org/...1/CC/c1cc14650e linked by Metrodorus, we can see that the C60 is pushing the phospholipids up out of the membrane plane, which is likely to cause reduced mobility and other issues. If the benefit provided by the C60 outweighs these issues, that's fine.

I saw this image in that article and it jumped out at me as bogus. I think these guys just took an existing 3D model of a membrane and translated the phospholipids out of the plane to make room for the curiously-clumped C60's. If you built an all-atom model of a membrane in water with appropriate counterions and boundary conditions, starting with this C60 configuration, and ran a few nsec of molecular dynamics on it, I would expect those C60's to disperse, the phospholipid chains to nestle around them, and the head groups to come back into the plane of the rest of the membrane. The model they show here didn't come from an experimental method or a simulation; I think it was just built that way to illustrate that based on the instrumental measurements they made, the data is best explained by C60 being inside the membrane. However, the details of this structure don't make thermodynamic sense.

There probably is a point at which membranes could be overloaded, although based on lifespan, it doesn't sound like Baati et al. hit it with the rats.

Edit: if I hadn't gotten a phone call while I was composing this, maybe I would have finished it before Metrodorus posted that nice simulation data.

Edited by niner, 19 June 2012 - 02:00 AM.

[Metrodorus]

A slightly longer cell modelling video - from the same studio

[niner]

...snip...
That said, I believe the "Cell-Membrane-ROS-Scavenging-As-Essential Mechanism-Explanation" folks should have have a backup hypothesis. The longer term life span enhancing effects experienced by the Baati rats have to be explained somehow. Earlier up thread, niner had tied these effects specifically to the C60 extended stay in the membrane hypothesis.
...snip...

I have to disagree; it is enough.

Pigeons have a 5-fold higher maximum lifespan than rats (35 vs. 7 years) with a similar weight and metabolic rate. Birds have vastly superior lungs and mitochondria compared to mammals, and live far longer.

Improved mitochondria function alone is enough.

I agree that improving mitochondrial function is huge, but I think what wccaguy wants to know is, what's the backup explanation if it should be demonstrated that the C60-fatty acid adducts don't hang around for very long? I can't think of a good backup that doesn't involve a lot of hand waving, but then again, do we need a backup? At the moment there is solid evidence that fullerenes get into membranes, particularly the mitochondrial membrane. As long as the cell stays alive, I don't see any reason for the adduct to leave, other than random statistical mechanics. Given the partition coefficient of a compound like the adduct, that sort of process is going to take a long time. I don't think that the fullerene content of the mitochondria will remain high forever. My guess would be that people would need to 'top up' every year or two. Eventually, I expect that a radiolabel experiment will shed some light on the rate of adduct loss.

[HighDesertWizard]

If the fullerene adducts generated in olive oil accumulate in the liver, then they may be redistributed from there to other organs.

In the last few days, in multiple posts, the idea has been floating around that C60 accumulates entirely/mostly/importantly in the liver. I understand the idea came from some more general study. That's not what the Baati study shows.

The Baati study says that the organs showing evidence of C60 accumulation were the blood, liver, urine, spleen, and brain. More specifically, the Baati rats showed "numerous spleen macrophages laden C60 crystals."

Microscopic examination at D8 of the spleen reticuloendothelial system (RES), where the highest concentrations are observed, shows the presence of some C60 aggregates that are larger and more numerous after i.p. administration (Fig. 2c and d) than after o.g. (Fig. 2a, b): thus C60 concentrations reached the limit of solubility in spleens. In contrast there are no observable deposits inside the livers in all cases indicating that C60 concentrations in these organs are not high enough to trigger precipitation.

While transmission electron microscopy (TEM) at D8 after i.p. administration shows numerous spleen macrophages laden C60 crystals (Fig. 2e) only some C60 crystals were observed inside liver macrophages and very rare crystals in lung (Fig. 2f) and kidney cells (Fig. 2g).

The rat spleen C60s, "laden with macrophages" were important enough to the Baati team that they thought to include snapshots of these C60s as the Figure 2 series.

Meanwhile, Kevin Tracey et al, in a 2008 study of the spleen, TNF, macrophages, and their role in the Cholinergic Anti-Inflammatory Pathway found...

Macrophages Are the Major Source of Spleen TNF During Endotoxemia... We previously established that the cholinergic antiinflammatory pathway regulates TNF production in the spleen (12), but the cellular source of spleen TNF during endotoxemia was previously unknown. Macrophages, a component of the reticuloendothelial system, are a major source of TNF in endotoxemia (18).

Given the profound relationships TNF has with several different dimensions of Longevity, including with major Longevity Genes and in Human Population Studies, this seems important.

Even more so, when the study about TNF inhibition in-vitro that Metrodorus found is added to the mix...

Going back to that TNF-alpha discussion earlier - there is one fullerene study that explicitly included TNF-alpha in the experimental design:

http://www.ncbi.nlm....les/PMC2775692/

The key finding was:
C60 significantly suppressed the TNF-α-induced production of proinflammatory cytokines in synovial fibroblasts, synovial infiltrating lymphocytes and macrophagesin vitro.

This seems significant enough that I'll do more looking around...

Edited by wccaguy, 19 June 2012 - 04:00 AM.

[HighDesertWizard]

TNF promotes/induces/increases ROS, damage, and/or oxidative stress in the Mitochondria...

Rapid reactive oxygen species production by mitochondria in endothelial cells exposed to tumor necrosis factor-alpha is mediated by ceramide

TNF-induced mitochondrial damage: a link between mitochondrial complex I activity and left ventricular dysfunction

TNF-alpha-induced mitochondrial oxidative stress and cardiac dysfunction: restoration by superoxide dismutase mimetic Tempol

Successful tumour necrosis factor (TNF) blocking therapy suppresses oxidative stress and hypoxiainduced mitochondrial mutagenesis in inflammatory arthritis

---------------------------------------
Transcriptional control of mitochondrial biogenesis and its interface with inflammatory processes

Background
Cells avoid major mitochondrial damage and energy failure during systemic inflammatory states, such as severe acute infections, by specific targeting of the inflammatory response and by inducing anti-inflammatory and anti-oxidant defenses. Recent evidence indicates that these cell defenses also include mitochondrial biogenesis and the clearance of damaged mitochondria through autophagy.
Scope of review
This review addresses a group of transcriptional signaling mechanisms that engage mitochondrial biogenesis, including energy-sensing and redox-regulated transcription factors and co-activators, after major inflammatory events.
Major conclusions
Stimulation of the innate immune system by activation of toll-like receptors (TLR) generates pro-inflammatory mediators, such as tumor necrosis factor-α (TNF-α)and interleukin-1β (IL-1β), necessary for optimal host defense, but which also contribute to mitochondrial damage through oxidative stress and other mechanisms. To protect its energy supply, host cells sense mitochondrial damage and initiate mitochondrial biogenesis under the control of an inducible transcriptional program that also activates anti-oxidant and anti-inflammatory gene expression. This multifunctional network not only increases cellular resistance to metabolic failure, oxidative stress, and cell death, but promotes immune tolerance as shown in the graphical abstract.

Edited by wccaguy, 19 June 2012 - 04:25 AM.

[HighDesertWizard]

I agree that improving mitochondrial function is huge, but I think what wccaguy wants to know is, what's the backup explanation if it should be demonstrated that the C60-fatty acid adducts don't hang around for very long? I can't think of a good backup that doesn't involve a lot of hand waving, but then again, do we need a backup?

Yes. That's what I was thinking. I think having a backup is a good idea. The more Explanations the better, IMHO.

Edited by wccaguy, 19 June 2012 - 04:34 AM.

[Logic]

Thx for the vids Metrodorus.
They and similar vids on YouTube have/are/will help my understanding of biology tremendously!

[HighDesertWizard]

Meanwhile, Kevin Tracey et al, in a 2008 study of the spleen, TNF, macrophages, and their role in the Cholinergic Anti-Inflammatory Pathway found...

Macrophages Are the Major Source of Spleen TNF During Endotoxemia... We previously established that the cholinergic antiinflammatory pathway regulates TNF production in the spleen (12), but the cellular source of spleen TNF during endotoxemia was previously unknown. Macrophages, a component of the reticuloendothelial system, are a major source of TNF in endotoxemia (18).

Given the profound relationships TNF has with several different dimensions of Longevity, including with major Longevity Genes and in Human Population Studies, this seems important.

Here's the key Kevin Tracey led study, published before the one above, that demonstrated the spleen was a significant source of TNF in the blood...

Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis

Here we show that vagus nerve stimulation fails to inhibit tumor necrosis factor (TNF) production in splenectomized animals during lethal endotoxemia. Selective lesioning of the common celiac nerve abolishes TNF suppression by vagus nerve stimulation, suggesting that the cholinergic pathway is functionally hard wired to the spleen via this branch of the vagus nerve. Administration of nicotine, an α7 agonist that mimics vagus nerve stimulation, increases proinflammatory cytokine production and lethality from polymicrobial sepsis in splenectomized mice, indicating that the spleen is critical to the protective response of the cholinergic pathway. These results reveal a specific, physiological connection between the nervous and innate immune systems that may be exploited through either electrical vagus nerve stimulation or administration of α7 agonists to inhibit proinflammatory cytokine production during infection and tissue injury.

[Metrodorus]

I was doing a google scholar search for 'fullerene enzyme stability' when I came across this paper:

http://csmres.co.uk/...loads/lynch.pdf


Protein-nanoparticle interactions

[PDF] from csmres.co.uk
I Lynch… - Nano Today, 2008 - Elsevier
... The highly curved surface of C 60 fullerenes have also been shown to enhance
enzyme stability



If fullerene promotes enzyme stability ( pointing perhaps to wider protein stability), then this would be another piece of the puzzle explaining a longevity effect. This (2007) study quoted below points to such an effect on enzyme stability.

http://www.ingentaco...020004/art00063


Enhanced stability of enzymes adsorbed onto nanoparticles

P Asuri, SS Karajanagi, AA Vertegel… - … of Nanoscience and …, 2007 - ingentaconnect.com

Edited by Metrodorus, 19 June 2012 - 07:19 AM.

[HighDesertWizard]

A supporting study for the Immunomodulatory Activity of Fullerenes via its effect on macrophages associated with liver cancer...

Tumor-Inhibitory Effect and Immunomodulatory Activity of Fullerol C60(OH)x

The tumor-inhibitory effect of C₆₀(OH)_x was tested on the murine H22 hepatocarcinoma model. Doses of 0.2 and 1.0 mg kg⁻¹ body weight both showed significant antitumor activity with tumor inhibition rates of 31.9 and 38.4%, respectively, when mice were treated for 17 consecutive days. The damnification of liver was prominently reduced. Furthermore, histological examination indicated that an envelope of fibroblasts and lymphocytes was formed surrounding tumor tissues in the C₆₀(OH)_x-treated group, which inhibited the infiltration of tumor to the neighboring normal skeleton muscle tissues. To understand the antitumor mechanism, the immunomodulatory activity of C₆₀(OH)_xwas investigated. The results indicate that C₆₀(OH)_x enhances the phagocytosis of peritoneal macrophages and elevates the activity of arginase and acid phosphatase in vivo. The tumor necrosis factor alpha production of C₆₀(OH)_x-treated macrophages also increases in vitro. These results suggest that C₆₀(OH)_x can enhance the innate immunity of tumor-bearing mice, and therefore inhibits growth of the tumor.

Edited by wccaguy, 19 June 2012 - 11:33 AM.

[HighDesertWizard]

I believe I've now posted much of the detailed evidence supporting another--the third?--Explanation of the life span extension Baati study result. As you may have observed, from time to time, I reach too far. If this Explanation doesn't turn out to be another instance of my reaching too far, I'll summarize the Explanation more formally in the next few days. At the moment, and after some sleep, I can't think of any evidence that Falsifies it. Also, it is a Hard to Vary Theory. I'm in a great hurry to get this done so this post may not contain every point it ought to contain. Consider it a first draft. The key elements of this Explanation of the Baati Study Result go something like this...

• Baati states that the rat spleens, among a few other organs, were unique in accumulating C60s in that the C60s were "heavily laden" with macrophages. (See Baati, et al, 2012)

• Baati states that "C60 concentrations reached the limit of solubility in spleens." (See Baati, et al, 2012)

• As I understand the study, (virtually) all the C60s in the rat spleens cleared with a few tens of hours. (See Baati, et al, 2012)

• Among other things, Kevin Tracey's work on the Cholinergic Anti-Inflammatory Pathway (CAIP) makes it clear that the spleen is a key organ of the the nervous and innate immune systems in storing the macrophages, including TNF Cytokines, that are released when necessary for Host Defense. (See my posts above.)

• An understanding of this Explanation requires some understanding of the CAIP. (See especially Kevin Tracey et al, 2007, for an overview of the CAIP.)

• TNF has been found to play a non-trivial role, in a non-trivial number of dimensions and studies, in Extreme Longevity. (See the Longecity thread I created on TNF.)

• The role of TNF in Extreme Longevity has specifically to do its role in the promotion of Immune, Auto-Immune, Inflammatory, and tumorous diseases.

• TNF promotes, induces, and/or increases ROS, damage, and/or oxidative stress in the Mitochondria. (See my post above.)

• I haven't had the time to get my head around enough studies yet, but I'm relatively certain it will also turn out that TNF has profound impact on global DNA (de)Methylation.

• Thus far, all known anecdotal reports to date of the use of the Baati potion in humans is consistent with profound TNF reduction. (See the anecdotal reports in this and other Longecity threads.)

Among other potential positive effects of C60/OO on life spans in the Baati study, the significant reduction of TNF laden macrophages from the C60/OO rat spleens profoundly reduced the probability of their earlier death by tumors and other diseases associated with the diseases of aging associated with Immune System and/or Inflammation related dysfunction.

Edited by wccaguy, 19 June 2012 - 12:06 PM.

[niner]

In the last few days, in multiple posts, the idea has been floating around that C60 accumulates entirely/mostly/importantly in the liver. I understand the idea came from some more general study. That's not what the Baati study shows.

The Baati study says that the organs showing evidence of C60 accumulation were the blood, liver, urine, spleen, and brain. More specifically, the Baati rats showed "numerous spleen macrophages laden C60 crystals."

Microscopic examination at D8 of the spleen reticuloendothelial system (RES), where the highest concentrations are observed, shows the presence of some C60 aggregates that are larger and more numerous after i.p. administration (Fig. 2c and d) than after o.g. (Fig. 2a, b): thus C60 concentrations reached the limit of solubility in spleens. In contrast there are no observable deposits inside the livers in all cases indicating that C60 concentrations in these organs are not high enough to trigger precipitation.

While transmission electron microscopy (TEM) at D8 after i.p. administration shows numerous spleen macrophages laden C60 crystals (Fig. 2e) only some C60 crystals were observed inside liver macrophages and very rare crystals in lung (Fig. 2f) and kidney cells (Fig. 2g).

The rat spleen C60s, "laden with macrophages" were important enough to the Baati team that they thought to include snapshots of these C60s as the Figure 2 series.

Meanwhile, Kevin Tracey et al, in a 2008 study of the spleen, TNF, macrophages, and their role in the Cholinergic Anti-Inflammatory Pathway found...

Macrophages Are the Major Source of Spleen TNF During Endotoxemia... We previously established that the cholinergic antiinflammatory pathway regulates TNF production in the spleen (12), but the cellular source of spleen TNF during endotoxemia was previously unknown. Macrophages, a component of the reticuloendothelial system, are a major source of TNF in endotoxemia (18).

Given the profound relationships TNF has with several different dimensions of Longevity, including with major Longevity Genes and in Human Population Studies, this seems important.

I think you're taking a wrong turn here. Macrophages do all kinds of things. They can be involved in inflammatory processes typically aimed at attacking microbes, in which they produce TNF. One of their other jobs is eating junk, like said microbes, or any particles that find their way into general circulation, which would include C60 aggregates. These are separate effects; phagocytosing a C60 particle after an ip megadose wouldn't be likely to induce or repress TNF production in general.

Note that this C60 aggregation was a consequence of i.p. injection, which is a good reason to take this stuff orally rather than jabbing a needle in your tummy. It was also a consequence of a 4mg/kg dose, IIRC, which would also be ill-advised.

[Turnbuckle]

Another point in support of the epigenetic theory of action: As previously discussed, a theoretical model suggests that C60 binds to the grooves of double stranded DNA, and the study quoted below shows that the model is correct (for water soluble C60, at least)--

Fullerenol C₆₀(OH)₂₄ binds significantly to the phosphate backbone of native dsDNA and to base-pairs within the major groove of sodium salt of dsDNA.

The theoretical model predicted that plain C60 would bind to the minor grooves and the fullerenol study found binding to the major grooves, but binding with either groove has been found to be associated with inhibitors of methyltransferase. The difference may be in the size of the fullerene or fullerenol molecule, and if so, a solution of mixed fullerenes--C60 plus C70, for instance--ought to be a more powerful inhibitor as it might bind to both grooves at once.

Edited by Turnbuckle, 19 June 2012 - 01:06 PM.

[niner]

Meanwhile, Kevin Tracey et al, in a 2008 study of the spleen, TNF, macrophages, and their role in the Cholinergic Anti-Inflammatory Pathway found...

Macrophages Are the Major Source of Spleen TNF During Endotoxemia... We previously established that the cholinergic antiinflammatory pathway regulates TNF production in the spleen (12), but the cellular source of spleen TNF during endotoxemia was previously unknown. Macrophages, a component of the reticuloendothelial system, are a major source of TNF in endotoxemia (18).

Given the profound relationships TNF has with several different dimensions of Longevity, including with major Longevity Genes and in Human Population Studies, this seems important.

Here's the key Kevin Tracey led study, published before the one above, that demonstrated the spleen was a significant source of TNF in the blood...

Splenectomy inactivates the cholinergic antiinflammatory pathway during lethal endotoxemia and polymicrobial sepsis

I changed the emphasis in the above quote to point out that this example of splenic involvement is specific to lethal endotoxemia/sepsis. That's a radically different situation than when the spleen picks up particulate junk in a healthy but very heavily dosed animal. I don't think that we can connect the two just because the spleen is involved in both cases.

[HighDesertWizard]

I think you're taking a wrong turn here. Macrophages do all kinds of things. They can be involved in inflammatory processes typically aimed at attacking microbes, in which they produce TNF. One of their other jobs is eating junk, like said microbes, or any particles that find their way into general circulation, which would include C60 aggregates. These are separate effects; phagocytosing a C60 particle after an ip megadose wouldn't be likely to induce or repress TNF production in general.

Note that this C60 aggregation was a consequence of i.p. injection, which is a good reason to take this stuff orally rather than jabbing a needle in your tummy. It was also a consequence of a 4mg/kg dose, IIRC, which would also be ill-advised.

Hey niner... Thanks for looking at this...

• The C60s ate the macrophages in the Baati rats and not the other way around.

• Thanks for making out the i.p. injection point. I hadn't looked at that closely but I will.

[HighDesertWizard]

I changed the emphasis in the above quote to point out that this example of splenic involvement is specific to lethal endotoxemia/sepsis. That's a radically different situation than when the spleen picks up particulate junk in a healthy but very heavily dosed animal. I don't think that we can connect the two just because the spleen is involved in both cases.

Thanks... I take your point... But I think this objection won't turn out to be significant. I think Kevin Tracey would say that the spleen is involved in storage of macrophages types of all sorts...

I appreciate ANY and ALL objections to the Explanation I'm proposing.

Thank you!

Edited by wccaguy, 19 June 2012 - 12:24 PM.

[Metrodorus]

Mathematical modelling of fullerenes of various diameters in lipid bilayers (full article) (2011)

http://utd.edu/~son0...entnano2011.pdf

[niner]

The C60s ate the macrophages in the Baati rats and not the other way around.

That can't be right. Macrophages are about a thousand times larger than a C60 molecule, for one thing. I thought that the C60 came out of solution in the form of a crystal or aggregate, and these were seen in the macrophages... There's really no way I can see that C60 could eat a macrophage.

[smithx]

Mathematical modelling of fullerenes of various diameters in lipid bilayers (full article) (2011)
http://utd.edu/~son0...entnano2011.pdf

That looks a lot better. Their diagrams are very similar to the other simulation you posted.

The diagram I posted from that other article resembles C540 more than C60.

[HighDesertWizard]

The C60s ate the macrophages in the Baati rats and not the other way around.

That can't be right. Macrophages are about a thousand times larger than a C60 molecule, for one thing. I thought that the C60 came out of solution in the form of a crystal or aggregate, and these were seen in the macrophages... There's really no way I can see that C60 could eat a macrophage.

niner... You're right... I misinterpreted a line from the Figure 2 caption. I'll look to see what needs to be changed in the statement of the Explanation. Good catch... Thanks.

I don't think it changes the essential point, namely, that the C60s did something profound to macrophages inside the spleen and the spleen is an important source of TNF for purposes of Host Defense.

I'll look to see what the C60 did... Meanwhile, we do know, from the study Metrodorus posted, that C60 reduces TNF, and we know from the studies I posted above that TNF reduction leads to reduction of ROS, damage, and oxidation for cell mitochondria per the studies I posted yesterday.

http://www.ncbi.nlm....pubmed/17999162

Given (1) the numerous profound relationships of TNF to Extreme Longevity and (2) the coincident, unusually positive life span result of Baati, I think this Explanation around spleen based macrophages with TNF/C60s is worth more research and reflection...

I also believe there will turn out to be linkages from this Explanation to other Explanations (of the Baati result as well as the other Longevity studies implicating TNF as being important). I've believed for a while now that a key test of any Explanation will turn out to be how "it fits and confirms" findings from other Explanation dimensions.

Thanks again for spotting my error...

Edited by wccaguy, 19 June 2012 - 08:31 PM.

[niner]

I'll look to see what the C60 did... Meanwhile, we do know, from the study Metrodorus posted, that C60 reduces TNF leading to reduction of ROS, damage, and oxidation for cell mitochondria per the studies I posted yesterday.

http://www.ncbi.nlm....pubmed/17999162

I think the causal chain in this paper is TNF caused damage by a ROS-based mechanism which was interrupted by the polyhydroxy C60. This was an in vitro experiment; it looks like TNF was added to the cell medium in the presence or absence of different C60 preparations.

Here's the abstract:

Pharm Res. 2008 Jun;25(6):1365-76.
Modulation of tumor necrosis factor-mediated cell death by fullerenes.
Harhaji L, Isakovic A, Vucicevic L, Janjetovic K, Misirkic M, Markovic Z, Todorovic-Markovic B, Nikolic N, Vranjes-Djuric S, Nikolic Z, Trajkovic V.

Institute for Biological Research, Belgrade, Serbia.

PurposE: The fullerene (C60/C70 mixture-C60/70) nanocrystalline suspension prepared by solvent exchange method using tetrahydrofyran (THF/nC60/70) and polyhydroxylated C60/70 [C60/70(OH)n] were compared for their ability to modulate cytotoxicity of the proinflammatory cytokine tumor necrosis factor (TNF).
MATERIALS AND METHODS:

TNF-induced cytotoxicity was assessed in L929 fibrosarcoma cells by crystal violet assay. The type of cell death (apoptosis/necrosis), production of reactive oxygen species, mitochondrial depolarization and caspase activation were determined by flow cytometry using the appropriate reporter dyes.
RESULTS:

THF/nC60/70 augmented, while C60/70(OH)n reduced the cytotoxicity of TNF. The numbers of cells undergoing apoptosis/necrosis, as well as of those displaying the activation of apoptosis-inducing enzymes of caspase family, were respectively increased or reduced by THF/nC60/70 or C60/70(OH)n. The antioxidant N-acetylcysteine and mitochondrial permeability transition inhibitor cyclosporin A each partly blocked the cytotoxic action of TNF, indicating the involvement of oxidative stress and mitochondrial dysfunction in the TNF cytotoxicity. Accordingly, THF/nC60/70 or C60/70(OH)n potentiated or suppressed, respectively, TNF-triggered oxidative stress and mitochondrial depolarization.
CONCLUSION:

The ability of different fullerene preparations to modulate TNF-induced oxidative stress and subsequent cell death suggests their potential value in the TNF-based cancer therapy or prevention of TNF-dependent tissue damage.

PMID: 17999162

The fact that the THF/nC60 made TNF more toxic is interesting. We know that fullerene products made in THF have their own set of toxicities that are due to THF artifacts. We've also seen reports of various problems with nC60, a nanoparticulate version. The avoidance of this was likely the point of Baati's preparation method that involved filtration and centrifugation. So this stuff is kind of doubly jinxed; it's hard to say what is the real cause of its toxicity enhancement.

Edited by niner, 19 June 2012 - 08:39 PM.