231 replies to this topic

[sensei]

I'm not sure if it's been previously discussed in this thread, but the original C60 paper by Baati appeared to demonstrate longevity effects that might have been by olive oil alone.  This paper and the work by the Brunet Lab points to unique life extension properties of MUFAs.  It may not be the polyphenols, but MUFAs themselves where there is some communication between germline cells and the intestine that are involved in a deficiency of the H3K4me3 methyltransferase (compass chromatin complex) in germline cells and fat accumulation in the intestine.  MUFAs alone seem to be sufficient for life extension in C. Elegans and mice.

 

 

Not exactly,

 

While the C60 only group did have a longer lifespan than the controls, the statistical comparison to the known lifespan range of Male Wistar Rats was consistent with the OO only group -- even if it was in the +2 SD range of normal lifespan.

 

At least one (possibly more) C60OO rat exceeded the maximum known wistar rat lifespan by several months

Edited by sensei, 03 December 2017 - 08:09 PM.

[Kentavr]

Эксперимент с C60 и витамином E

 

Тип оливкового масла, используемого в первоначальном исследовании крысы, отличался высоким уровнем E, и, возможно, E является активным ингредиентом.

 

Примечание. Я добавил намного больше E, чем вероятно, чтобы убедиться, что я получил эффект, но я не дал ему много времени, чтобы отреагировать.

 

Ацетатная форма

80 мг / мл d-альфа-токоферилацетата в MCT-масло с максимальным содержанием C60 (около 7 мг / мл)

Встряхивают в янтарной бутылке и дают сидеть в темноте в течение 4 часов.

 

Результат: ½ чайной ложки → фактически ноль.

Это неудивительно, так как ацетатная форма довольно нереактивна. Это то, что я использовал раньше, и, вероятно, почему я не видел для него никакого преимущества.

 

Неацетатная форма

Та же базовая смесь C60, но со смешанными токоферилами с одинаковой общей концентрацией -

d-альфа-токоферил + d-гамма, d-дельта и d-бета (марка Solgar)

Встряхивают в янтарной бутылке и дают сидеть в темноте в течение 4 часов.

 

Результат: ½ чайной ложки → хороший эффект на упражнение, равный 1 tsp C60 + CoQ10 без облучения.

Никакое нервное чувство, но огромное влияние на кровяное давление. Это продолжалось 24 часа и потребовало 4 раза обычного лекарства от гипертонии, чтобы снизить его.

 

В общем и целом-

Неацетатные токоферилы очень интересны, но 80 мг / мл E слишком высоки. Может быть, в десять раз слишком высоко. Может быть, сто. В то время как E, как говорят, возбуждает сердце (по словам  Эвана Шут, MD ), у меня никогда не было этой реакции раньше, поэтому C60, похоже, потенцирует эффект.

 

 

Perhaps it is better to use tocotrienols?

[Turnbuckle]

Perhaps it is better to use tocotrienols?

 

 

Perhaps so. I prepared some and found it not as good as with HT. See my post #128. Note the MCT oil dissolves many types of plastics, including the container shown in that post. See also post 12 in my "red light" thread.

Edited by Turnbuckle, 01 July 2018 - 09:00 PM.

[ortcloud]

Anyone still experimenting with c60 hydroxytyrosol mixtures?

 

I ran across some 99% hydroxtyrosol oil the other day from Seprox.

 

 

[Engadin]

Unfortunately, Seprox is gone as May, 15th. 2020. Here in spanish. Its web, therefore, is a zombie one.

[ortcloud]

Unfortunately, Seprox is gone as May, 15th. 2020. Here in spanish. Its web, therefore, is a zombie one.

 

WTF !

 

Some companies make great products but have no idea how to market them, what a shame.

[OlderThanThou2]

Could the lifespan extension of C60OO be due to an increase in catalase level inside the mitochondria?

 

This study shows that increasing MnSOD in mice mitochondria does not increase lifespan:

 

"Overexpression of Mn Superoxide Dismutase Does Not Increase Life Span in Mice"

https://www.ncbi.nlm...les/PMC2759571/

 

However an increase in catalase in mitochondria increases lifespan of mice by 21%:

"Second, Rabinovitch’s group showed that overexpressing catalase in mitochondria increased the life span of mice by 21%"

 

Here is the study:

 

Extension of murine life span by overexpression of catalase targeted to mitochondria

https://pubmed.ncbi....h.gov/15879174/

Also Olive oil does increase catalase:

 

Extra virgin olive oil (EVOO) consumption and antioxidant status in healthy institutionalized elderly humans https://pubmed.ncbi....h.gov/23642776/

"Recent studies show that the elderly have increased oxidative stress and impaired antioxidant defense systems. Our study aims to evaluate the effects of daily consumption of EVOO in the healthy institutionalized elderly. We studied anthropometric, biochemical and antioxidant parameters in 62 subjects aged 65-96 years after a 6-week daily intake of polyphenol-rich EVOO with high oleuropein derivative contents. Subjects were divided into a control group (CG) who maintained their dietary habits (n=39) and an olive group (OG) who consumed EVOO as the only added fat, plus a daily dose of 50ml (n=23). We found a significant reduction of total cholesterol (TC), HDL, LDL and TGs in OG subjects and a significant increase of HDL levels. There was no significant variation in the CG parameters. In OG the total antioxidant capacity (TAC) in plasma increased with significant differences over CG. Plasma hydroxytyrosol (OH-Tyr) concentration showed a significant increase after EVOO intervention. Daily consumption of EVOO was found to have positive effects on lipid profiles, OH-Tyr levels and TAC. The results also show a significant increase of catalase (CAT) in erythrocytes and a decrease (p<0.05) in superoxide dismutase (SOD) and glutathione peroxidase (GH-PX) activity after EVOO intake. To our knowledge, no other study has examined the effects of EVOO consumption on biochemical parameters, antioxidant capacity and antioxidant enzyme activity in healthy elderly subjects. In conclusion, our results show that nutritional intervention with EVOO improves antioxidant status in healthy elderly people."

 

OO polyphenols and fullerenes could also perhaps neutralize H2O2 inside the mitochondria besides an effect on catalase.

 

 

 

 

 

 

Edited by OlderThanThou2, 16 August 2020 - 05:11 PM.

[Turnbuckle]

Could the lifespan extension of C60OO be due to an increase in catalase level inside the mitochondria?

 

 

 

I now think that C60 blocks UCP2 pores in SC mitochondria. If done correctly, this can increase SC numbers and prolong life. If done incorrectly, it can reduce SC numbers.

[OlderThanThou2]

So you don't think OO has anything to do with it after all?

 

Regarding C60 blocking the UCP2 pores would it have to have the precise size of those pores for that? Do we know the size of those pores? 

 

Maybe a stupid question, would it be possible to know if a molecule has attached to C60, like after being put in OO, or in the urine to see if it would get rid of something in the body?

[Turnbuckle]

So you don't think OO has anything to do with it after all?

 

Regarding C60 blocking the UCP2 pores would it have to have the precise size of those pores for that? Do we know the size of those pores? 

 

Maybe a stupid question, would it be possible to know if a molecule has attached to C60, like after being put in OO, or in the urine to see if it would get rid of something in the body?

 

 

The point of this thread was the hypothesis that polyphenols had something to do with longevity results of C60 dissolved in olive oil. Olive oil is just a vehicle that is a triglyceride of mostly oleic acid, and other oils seem to work just as well, such as MCT oil, which has no oleic acid. As for blocking UCP2 pores, this appears to be a backdoor for stimulating stem cells into activity. SC mitochondria are loaded up with them, and they disappear just before stem cells wake up and begin dividing. These pores keep mitochondria quiescent by providing proton leakage, which stops ATP production. Protons are fantastically smaller than C60 molecules, but in water they from hydronium ions which are larger, and which are likely surrounded by clusters of water molecules, making them larger still. The UCP2 channel is a bit like a funnel, so blocking it with a spherical molecule seems possible. C60 is not unique in this regard. A cross-linker such as Genipin can also block them and stimulate SCs, but has a lot of side effects.

 

See the later thread, Stem cell self-renewal with C60

[OlderThanThou2]

Alright, perhaps there might be reasons why a spherical shape would be better able at blocking a funnel. Perhaps it is more likely to can come in contact with the walls of the funnel at 3 spots instead of 2 for a regular shape?  But the question then is, why doesn't it block other types of pores? I take it there might be lots or those in the body so it would take a lot of luck for C60 to block just the right one. But perhaps other types of pores would be blocked as well.

 

Also, if stem cells production is increased, wouldn't that do in sort that the Hayflick limit would be reached sooner? C60 would have to be able to lengthen the telomeres to compensate.  But I take it UCP2 pores also exist in  mitochondria of grown cells so blocking them might have an effect. If it prevents proton leakage, wouldn't it decrease oxidative stress on the telomeres and help them keep their length?

[Turnbuckle]

Alright, perhaps there might be reasons why a spherical shape would be better able at blocking a funnel. Perhaps it is more likely to can come in contact with the walls of the funnel at 3 spots instead of 2 for a regular shape?  But the question then is, why doesn't it block other types of pores? I take it there might be lots or those in the body so it would take a lot of luck for C60 to block just the right one. But perhaps other types of pores would be blocked as well.

 

Also, if stem cells production is increased, wouldn't that do in sort that the Hayflick limit would be reached sooner? C60 would have to be able to lengthen the telomeres to compensate.  But I take it UCP2 pores also exist in  mitochondria of grown cells so blocking them might have an effect. If it prevents proton leakage, wouldn't it decrease oxidative stress on the telomeres and help them keep their length?

 

 

It's only partly luck that C60 blocks those pores. Evolution would have designed them so nothing in the normal diet would block them. I suspect nanoparticles of gold or silver may also do the job, but C60 with fatty acid adducts would get a special pass into mitochondria,* and thus would be far more efficient. If it blocks other pores, it doesn't produce any significant effect, or blocks them for such a short time that nothing untoward happens. As for the Hayflick limit, that doesn't apply, as embryonic stem cells like VSELs are immortal.

 

Other fullerenes may go elsewhere. C70, for instance, likes to hang out in the endoplasmic reticulum, where it can screw up protein folding.

Edited by Turnbuckle, 17 August 2020 - 04:39 PM.

[OlderThanThou2]

If your theory is correct that means that the more spherical a molecule is the more likely it is to block the hole. I looked at the 3D animation of Genipin, it is in spread relatively well 3 dimensions and in under certain angle the outer atoms look somewhat like a piece of sphere. Unless it's me who wants to see what I want to see..

 

https://chemapps.sto...(=C/C[C@H]12)CO

Edited by OlderThanThou2, 17 August 2020 - 05:05 PM.

[Turnbuckle]

If your theory is correct that means that the more spherical a molecule is the more likely it is to block the hole. I looked at the 3D animation of Genipin, it is in spread relatively well 3 dimensions and in under certain angle the outer atoms look somewhat like a piece of sphere. Unless it's me who wants to see what I want to see..

 

https://chemapps.sto...(=C/C[C@H]12)CO

 

I'd thought it was the cross linking activity of genipin that was responsible for its action, but seems not. The derivative AG (1,10-anhydrogenipin) is not a cross-linker but still blocks UCP2 pores.

 

Of interest, AG inhibits UCP2-mediated proton leak, closes KATP channels, and stimulates insulin secretion in a UCP2-dependent fashion. These results suggest that the cross-linking activity of genipin is not required for its biological activity as a UCP inhibitor.

https://www.cell.com...4131(06)00129-X

 

 

 

Perhaps it is a key in a lock type effect for genipin, and ball in a funnel for C60.

[OlderThanThou2]

Perhaps if the shape of the pore was known in detail it would be possible to take the inverse image to determine the exact shape of the key. Then perhaps an AI could try to match that shape against genipin and C60, or even thousands of molecules to find other ones that could block UCP2. With that technique and a bit of luck maybe it might be possible to find molecules that could block any type of pore.

[Turnbuckle]

Perhaps if the shape of the pore was known in detail it would be possible to take the inverse image to determine the exact shape of the key. Then perhaps an AI could try to match that shape against genipin and C60, or even thousands of molecules to find other ones that could block UCP2. With that technique and a bit of luck maybe it might be possible to find molecules that could block any type of pore.

 

 

There are certainly groups modeling those pores-- https://biophysicall...cts-2/projects/

[OlderThanThou2]

If I get it right the 6 UCPs are intertwined helices. The article abstract says:

 

ATP, the principal energy currency of the cell, fuels most biosynthetic reactions in the cytoplasm by its hydrolysis into ADP and inorganic phosphate. Because resynthesis of ATP occurs in the mitochondrial matrix, ATP is exported into the cytoplasm while ADP is imported into the matrix. The exchange is accomplished by a single protein, the ADP/ATP carrier. Here we have solved the bovine carrier structure at a resolution of 2.2 Å by X-ray crystallography in complex with an inhibitor, carboxyatractyloside. Six α-helices form a compact transmembrane domain, which, at the surface towards the space between inner and outer mitochondrial membranes, reveals a deep depression. At its bottom, a hexapeptide carrying the signature of nucleotide carriers (RRRMMM) is located. Our structure, together with earlier biochemical results, suggests that transport substrates bind to the bottom of the cavity and that translocation results from a transient transition from a ‘pit’ to a ‘channel’ conformation.

 

If I understand correctly these pores don't have the shape of a regular funnel. Instead the openings are small and there's a cavity inside. Perhaps this team of scientists would have an idea on what's so special about genipin that it is able to block UCP2, and also perhaps why C60 could do it as well.

[Turnbuckle]

If I get it right the 6 UCPs are intertwined helices. The article abstract says:

 

If I understand correctly these pores don't have the shape of a regular funnel. Instead the openings are small and there's a cavity inside. Perhaps this team of scientists would have an idea on what's so special about genipin that it is able to block UCP2, and also perhaps why C60 could do it as well.

 

 

That's the Adenine nucleotide translocator, not the UCP2 -- UCPs contain the three homologous protein domains of MACPs.

[OlderThanThou2]

Oops... I think it's getting a bit too complicated for me. 

[Encoded222]

The time period was too short in the study you referenced.  And the subjects were untrained.  There has been an informal test I know of, reported in the resveratrol forum* a few years ago:  A cycling coach noticed and unexpected performance improvement in athletes he was training, and he asked them what they were on.  Resveratrol.    He tried it on himself, taking 500 gram 98% resveratrol daily, for 45 days, measuring his own performance.   The conclusion he drew is resveratrol can improve aerobic performance but only if one is already fit and training like hell.  I know of no formal study in human athletes of similar duration.

 

(Interesting that the Latvian ergogenic drug of choice, meldonium, seems to share many pharmacological properties with resverarol.)

 

* the topic link is here

 

Noticed a remarkable increase in running cappacity too when I took resveratrol. Pretty sure it wasn't placebo, because I didn't expect something like this. Was really surprised.

[Encoded222]

(11)

One teaspoon of—

 

MCT oil (Viva Labs: “100% capric and caprylic acid.”)

0.6 mg/ml C60

0.8 mg/ml hydroxytyrosol (HT)

 

Did you try the MCT oil/C60 combo without the HT already?

There shouldn't be any significant effect if the PPs are doing the magic.

[Turnbuckle]

Did you try the MCT oil/C60 combo without the HT already?

There shouldn't be any significant effect if the PPs are doing the magic.

 

I no longer think this is a valid hypothesis. See post 220.