3585 replies to this topic

[pone11]

I'm not sure that adipose tissue consumption rates have much to do with the composition of membranes and how quickly that changes.  When we are fasting, we don't burn our membranes for energy-- If we did, we'd be dead in a hurry.  These are two very different categories of lipids.

 

That's also a great point, although do we have any estimate on the half life of cell membranes that use PUFA?

[sensei]

 

 

PUFAs are essential, but no one in this conversation ever said you shouldn't eat ANY of those fats.  Why do you bring that up?

 

I don't think any source you quoted proved the claim that "a 600 day half-life for ingested PUFAs bears no resemblance to known biochemical processes of the human body...."    Your own source said he couldn't get a number.  

 

What is your estimate for the half life of polyunsaturated fat?   At the end of the day, give us a credible number, not just a lot of hand waving about why Ray Peat's number is not great.  What's your number?  

 

Your source only implies that the right number is less than four years.  Fine.  Is it three?  Is it two?  Why is your number better than Peat's?   Can you prove it?

 

If the number is two years, then Niner's point is still valid.   

 

I don't have any need to defend Peat's point on half life.  But I don't think you have given us better information.  I accept that Peat's number is not precise and different people will argue it it higher or lower than some number based on more recent experiments.

 

I'd say months for total turnover at the most,  based on the way adipose cells release chemicals bound to stored fats.

 

And we do have evidence -- it's called the metabolism of marijuana. MJ is lipophylic and is stored in adipose tissue, only released upon lipolysis.

 

Metabolites of MJ are stored in adipose tissue and released as fat is released back into the body.  After heavy use, the metabolites are detectable for up to 77 days with a mean time to non-detection of 27 days. This implies an almost complete turnover of fat stores in that time, else persons would test positive 6 months, or even a year after abstinence which simply does not happen.

 

Excretion patterns of cannabinoid metabolites after last use in a group of chronic users.

 

The urinary excretion patterns of 86 chronic cannabis users were examined after their last cannabis use by two common screening methods, the semiquantitative EMIT-d.a.u. and the qualitative EMIT-st (Syva Company). We demonstrated that under very strictly supervised abstinence, chronic users can have positive results for cannabinoids in urine at 20 ng/ml or above on the EMIT-d.a.u. assay for as many as 46 consecutive days from admission, and can take as many as 77 days to drop below the cutoff calibrator for 10 consecutive days. For all subjects, the mean excretion time was 27 days. Subject excretion patterns were clearly biphasic, with initial higher rates of excretion not sustained. During the subsequent period of leveling off, most subjects had one or more separate sequences of cannabinoid-negative urine test results, lasting a mean of 3 days each and followed by at least one positive result. Demographic, body type, and drug history variables proved to be only moderate predictors of excretion patterns. Findings were discussed in the context of potential clinical and forensic application.

 

http://www.ncbi.nlm..../pubmed/3902318

 

And for a more appropriate comparison we should be looking at how long oleic acid based components remain in the membrane.  Are you suggesting that FA from olive oil stay in adipose or membranes for 2-3 years.

[pone11]

 

 

 

PUFAs are essential, but no one in this conversation ever said you shouldn't eat ANY of those fats.  Why do you bring that up?

 

I don't think any source you quoted proved the claim that "a 600 day half-life for ingested PUFAs bears no resemblance to known biochemical processes of the human body...."    Your own source said he couldn't get a number.  

 

What is your estimate for the half life of polyunsaturated fat?   At the end of the day, give us a credible number, not just a lot of hand waving about why Ray Peat's number is not great.  What's your number?  

 

Your source only implies that the right number is less than four years.  Fine.  Is it three?  Is it two?  Why is your number better than Peat's?   Can you prove it?

 

If the number is two years, then Niner's point is still valid.   

 

I don't have any need to defend Peat's point on half life.  But I don't think you have given us better information.  I accept that Peat's number is not precise and different people will argue it it higher or lower than some number based on more recent experiments.

 

I'd say months for total turnover at the most,  based on the way adipose cells release chemicals bound to stored fats.

 

And we do have evidence -- it's called the metabolism of marijuana. MJ is lipophylic and is stored in adipose tissue, only released upon lipolysis.

 

Metabolites of MJ are stored in adipose tissue and released as fat is released back into the body.  After heavy use, the metabolites are detectable for up to 77 days with a mean time to non-detection of 27 days. This implies an almost complete turnover of fat stores in that time, else persons would test positive 6 months, or even a year after abstinence which simply does not happen.

 

Excretion patterns of cannabinoid metabolites after last use in a group of chronic users.

 

The urinary excretion patterns of 86 chronic cannabis users were examined after their last cannabis use by two common screening methods, the semiquantitative EMIT-d.a.u. and the qualitative EMIT-st (Syva Company). We demonstrated that under very strictly supervised abstinence, chronic users can have positive results for cannabinoids in urine at 20 ng/ml or above on the EMIT-d.a.u. assay for as many as 46 consecutive days from admission, and can take as many as 77 days to drop below the cutoff calibrator for 10 consecutive days. For all subjects, the mean excretion time was 27 days. Subject excretion patterns were clearly biphasic, with initial higher rates of excretion not sustained. During the subsequent period of leveling off, most subjects had one or more separate sequences of cannabinoid-negative urine test results, lasting a mean of 3 days each and followed by at least one positive result. Demographic, body type, and drug history variables proved to be only moderate predictors of excretion patterns. Findings were discussed in the context of potential clinical and forensic application.

 

http://www.ncbi.nlm..../pubmed/3902318

 

And for a more appropriate comparison we should be looking at how long oleic acid based components remain in the membrane.  Are you suggesting that FA from olive oil stay in adipose or membranes for 2-3 years.

 

 

The marijuana evidence is poor.  The incorrect assumption is that marijuana has been stored uniformly across every adipose tissue.  Where is the proof of that?   If marijuana is stored only in some tissues, and those tissues end up metabolizing in 77 days, that says nothing about the overall metabolism of the remaining fats.

 

Where is your experimental evidence that all fats turnover in days?   That is your conjecture and if your evidence is marijuana studies that is much poorer evidence than the Hirsch study that your source criticized.   And your source didn't even want to make a guess about the real number.

 

I find several studies that either make their own conjectures at 1 to 4 years, or rely on Hirsch:

http://jn.nutrition..../3/925S.full#T3

http://www.jlr.org/c.../1/103.full.pdf

http://ajcn.nutritio...3/1/81.full.pdf

 

And here is the "controversial" Hirsch study:

http://ajcn.nutritio.../4/499.full.pdf

 

I don't find any studies that back your position, which isn't to say they don't exist.  But you haven't presented anything, and neither did the blog you quoted.

[sensei]

 

 

The marijuana evidence is poor.  The incorrect assumption is that marijuana has been stored uniformly across every adipose tissue.  Where is the proof of that?   If marijuana is stored only in some tissues, and those tissues end up metabolizing in 77 days, that says nothing about the overall metabolism of the remaining fats.

 

Where is your experimental evidence that all fats turnover in days?   That is your conjecture and if your evidence is marijuana studies that is much poorer evidence than the Hirsch study that your source criticized.   And your source didn't even want to make a guess about the real number.

 

I find several studies that either make their own conjectures at 1 to 4 years, or rely on Hirsch:

http://jn.nutrition..../3/925S.full#T3

http://www.jlr.org/c.../1/103.full.pdf

http://ajcn.nutritio...3/1/81.full.pdf

 

And here is the "controversial" Hirsch study:

http://ajcn.nutritio.../4/499.full.pdf

 

I don't find any studies that back your position, which isn't to say they don't exist.  But you haven't presented anything, and neither did the blog you quoted.

 

 

1. Every single one of those studies either cite Hirsch, or use Hirsch to validate their own assumptions. (look at the notes)

 

2. Tissue biopsies have shown that MJ metabolites are stored in all fatty tissues, even the TESTES./

 

3. We do understand biochemical processes much better now. Ingested fat is used for fuel or stored for future use depending on the amount of circulating blood sugar, and muscular energy demand. Yet when fat is used by the body it is not 100% of either ingested or stored.

 

If you are increasing fat stores, then obviously fat stays in the body longer. But if you are maintaining a stable weight, the fats turn over -- regardless if the % of various length FA remain the same.

 

If you are ketotic AT ALL FOR ANY REASON -- PURPOSEFUL OR NOT, large amounts of fat can be flushed from the body in days.

 

600 days is rubbish.  All YOUR Evidence uses Hirsch as a basis or outright cites his number.

[pone11]

 

 

 

The marijuana evidence is poor.  The incorrect assumption is that marijuana has been stored uniformly across every adipose tissue.  Where is the proof of that?   If marijuana is stored only in some tissues, and those tissues end up metabolizing in 77 days, that says nothing about the overall metabolism of the remaining fats.

 

Where is your experimental evidence that all fats turnover in days?   That is your conjecture and if your evidence is marijuana studies that is much poorer evidence than the Hirsch study that your source criticized.   And your source didn't even want to make a guess about the real number.

 

I find several studies that either make their own conjectures at 1 to 4 years, or rely on Hirsch:

http://jn.nutrition..../3/925S.full#T3

http://www.jlr.org/c.../1/103.full.pdf

http://ajcn.nutritio...3/1/81.full.pdf

 

And here is the "controversial" Hirsch study:

http://ajcn.nutritio.../4/499.full.pdf

 

I don't find any studies that back your position, which isn't to say they don't exist.  But you haven't presented anything, and neither did the blog you quoted.

 

 

1. Every single one of those studies either cite Hirsch, or use Hirsch to validate their own assumptions. (look at the notes)

 

2. Tissue biopsies have shown that MJ metabolites are stored in all fatty tissues, even the TESTES./

 

3. We do understand biochemical processes much better now. Ingested fat is used for fuel or stored for future use depending on the amount of circulating blood sugar, and muscular energy demand. Yet when fat is used by the body it is not 100% of either ingested or stored.

 

If you are increasing fat stores, then obviously fat stays in the body longer. But if you are maintaining a stable weight, the fats turn over -- regardless if the % of various length FA remain the same.

 

If you are ketotic AT ALL FOR ANY REASON -- PURPOSEFUL OR NOT, large amounts of fat can be flushed from the body in days.

 

600 days is rubbish.  All YOUR Evidence uses Hirsch as a basis or outright cites his number.

 

 

In the original Hirsch study, when they feed high polyfat diets to subjects for up to 10 WEEKS at a time, there are no changes in the adipose content of the patient.  How do you explain that if the adipose turns over rapidly?   From the Hirsch Study here:

http://ajcn.nutritio.../4/499.full.pdf

 

see page 508:

"Effects of Diet In adults in caloric balance, dietary effects on adipose tissue are produced only slowly; in short term studies no effects are seen.... After ten weeks on a formula containing forty percent of calories as corn oil, the adipose tissue of this subject was normal in fatty acid composition. Then, after thirty-eight days on a fat-free high carbohydrate formula, the adipose pattern was still unaffected. During ten weeks on high intakes of corn oil, this patient ingested more than 3.5 kg. of linoleic acid, an amount roughly three times that present in his entire adipose tissue. Yet, the adipose linoleic concentration did not rise. During thirty-eight fat-free days the patients caloric expenditure was of the same order of magnitude as the total caloric value of his entire adipose depot, yet body weight did not change nor was adipose composition altered.  Clearly, there must have been intense lipogenesis from carbohydrate; but, the lack of accumulation of 16:0 and 16:1 and lack of decrease in 18:2 strongly argues against the participation of the entire adipose depot in the new synthesis of fatty acids."

 

From the same page, Hirsch establishes that it took up to 160 WEEKS to make the adipose tissue reflect the polyfat composition of diet!   See the passage:

"When formulas rich in corn oil are fed over extremely long periods, slow changes in adipose composition are seen eventually, amid they continue until an adipose pattern is evolved which is very similar to that of the fed corn oil acids. Figure 10 is a composite of the adipose changes in eight different subjects receiving diets rich in corn oil (usually 40 per cent of calories ) from eight to 160 weeks. Changes are almost imperceptible up to twenty weeks. However, at 160 weeks the adipose tissue has become rich in diunsaturated acid (essentially all l8:2) and it closely resembles a mixture of corn oil and normal adipose triglyceride in proportions of 7 to 3. There is no reason to believe that even further adipose changes might not have occurred if the corn oil feedings had been continued for longer periods of time."

 

It's important to see from these direct measurement of adipose tissue that you cannot change the composition rapidly, either up OR down.

 

Finally, you are misreading your own blog reference about the criticism of Hirsch.   Hirsch was trying to develop a formula to extrapolate experimental data on adipose changes over time.    Your blog author never disputed the above experimental evidence of slow adipose changes.  His criticism was the formula used to generalize the effect.  He has the opinion that the formula overstates the actual turnover period, yet he is unable to commit to any specific number in reply to Hirsch.  I have no commitment to Hirsch's formula.  I do not care if the right number is two years or five years.   But I do respect the evidence, which is very clear that adipose composition changes very slowly over time, no matter what you do to the diet.

 

Using Marijuana in adipose tissue as a response to a study that actually measures the real fat composition of actual fat is completely ridiculous.   We don't know that marijuana is in every single fat cell; that is a completely different point than saying it distributes to different types of adipose tissues.  We don't even know that removing the marijuana from the adipose requires full use of the adipose for energy.   These marijuana studies measure marijuana metabolism.   Using them for adipose metabolism is grade D evidence.

 

Show us ONE study where they change the adipose fatty acid composition of a subject from diet alone and force a measurable change in polyfat composition of adipose tissues within 90 days.   No such study exists.  Studies that change polyfat composition rapidly all rely on starvation or exercise, not diet.   Ketosis is simulated starvation, so that is the dietary exception, but clearly use of ketosis to clean out fat stores is the stuff of experiments because 95% of the US population doesn't understand ketosis and would never use it.

Edited by pone11, 18 February 2015 - 07:59 PM.

[niner]

Marijuana getting in or out of an adipose cell isn't related to turnover of the lipids in the cell.  The canabinoids etc don't bind to the lipids, they just mingle among them.  It's a physical phenomenon, not a chemical one.  They just have a very long half life.

 

I still don't get why you guys are arguing over fat stored in adipose cells.

[sensei]

 

In the original Hirsch study, when they feed high polyfat diets to subjects for up to 10 WEEKS at a time, there are no changes in the adipose content of the patient.  How do you explain that if the adipose turns over rapidly?  

 

Easily, the body tends to store fats in the same %. unless you intentionally skew fat intake to virtually only 1 type (by feeding someone 40% of their dietary calories a day from corn oil), which Hirsch actually shows.  In fact he states you don't see any changes until 20 weeks.

 

Basically Hirsch proved that if you feed someone 40% of their calories from corn oil -- their body will eventually store that corn oil in their adipose tissues.  It's ridiculous on it's face. -- The reason for this is because there wasn't much of  ANY OTHER KIND OF FAT AVAILABLE TO STORE -- not because of it's half life.

 

I bet the same thing happens if you force feed people 800 calories of olive oil for 160 weeks -- their fat will be mostly oleic acid.

 

MJ metabolites serve the same function as if a study like Hirsch was conducted with radio-labeled PUFAS. (unfortunately they didn't do that much in 1960)  The metabolites are bound to the lipids stored in adipose cells and released upon lipolysis; thereby serving as a very good marker for fat turnover.

[sensei]

Marijuana getting in or out of an adipose cell isn't related to turnover of the lipids in the cell.  The canabinoids etc don't bind to the lipids, they just mingle among them.  It's a physical phenomenon, not a chemical one.  They just have a very long half life.

 

I still don't get why you guys are arguing over fat stored in adipose cells.

 

 

That's not entirely accurate (at least in rats and I don't expect it to be much different for humans.

 

Upregulation of lipolysis by ACTH or starvation results in increased release of THC from adipose tissues.

 

Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure

 

http://www.ncbi.nlm....les/PMC2782342/

Edited by sensei, 18 February 2015 - 08:39 PM.

[niner]

 

Marijuana getting in or out of an adipose cell isn't related to turnover of the lipids in the cell.  The canabinoids etc don't bind to the lipids, they just mingle among them.  It's a physical phenomenon, not a chemical one.  They just have a very long half life.

 

I still don't get why you guys are arguing over fat stored in adipose cells.

 

That's not entirely accurate (at least in rats and I don't expect it to be much different for humans.

Upregulation of lipolysis by ACTH or starvation results in increased release of THC from adipose tissues.

Reintoxication: the release of fat-stored Δ9-tetrahydrocannabinol (THC) into blood is enhanced by food deprivation or ACTH exposure

http://www.ncbi.nlm....les/PMC2782342/

 

 

In their Introduction, they say:

 

Under normal conditions, THC appears to passively diffuse from fat back into blood, thus explaining its long elimination half-life. However it is possible that under conditions of enhanced fat metabolism (lipolysis), THC might be released from fat at much higher concentrations than normal.

 

 

So you're correct in the event of something that causes unusual consumption of the stored fat in adipocytes.  I guess that means that if it's needed bad enough, the cell dumps its contents, or something to that effect.  I was thinking about the normal case, though, where it slowly comes out via passive diffusion.

[pone11]

Marijuana getting in or out of an adipose cell isn't related to turnover of the lipids in the cell.  The canabinoids etc don't bind to the lipids, they just mingle among them.  It's a physical phenomenon, not a chemical one.  They just have a very long half life.

 

I still don't get why you guys are arguing over fat stored in adipose cells.

 

Point taken.  But probably you would help end the argument if you published some data on half life of polyfats in cell membranes.  In effect, we are using adipose tissue composition and half life as a proxy for the membrane, in absence of relevant data.   That's wrong to do, but I don't have the relevant data.

[pone11]

 

 

In the original Hirsch study, when they feed high polyfat diets to subjects for up to 10 WEEKS at a time, there are no changes in the adipose content of the patient.  How do you explain that if the adipose turns over rapidly?  

 

Easily, the body tends to store fats in the same %. unless you intentionally skew fat intake to virtually only 1 type (by feeding someone 40% of their dietary calories a day from corn oil), which Hirsch actually shows.  In fact he states you don't see any changes until 20 weeks.

 

Basically Hirsch proved that if you feed someone 40% of their calories from corn oil -- their body will eventually store that corn oil in their adipose tissues.  It's ridiculous on it's face. -- The reason for this is because there wasn't much of  ANY OTHER KIND OF FAT AVAILABLE TO STORE -- not because of it's half life.

 

I bet the same thing happens if you force feed people 800 calories of olive oil for 160 weeks -- their fat will be mostly oleic acid.

 

MJ metabolites serve the same function as if a study like Hirsch was conducted with radio-labeled PUFAS. (unfortunately they didn't do that much in 1960)  The metabolites are bound to the lipids stored in adipose cells and released upon lipolysis; thereby serving as a very good marker for fat turnover.

 

 

He also fed low-fat high carbohydrate, and that diet also fails to change fatty acid compositions.  Why?

 

Obviously the body stores fats over time in the same composition of diet.   That's not the point at all we were arguing about.  The point is what happens to your existing fat stores, not the new ones from diet.  You are arguing they change over rapidly.  Where is the evidence of that?

[sensei]

 

Obviously the body stores fats over time in the same composition of diet.   That's not the point at all we were arguing about.  The point is what happens to your existing fat stores, not the new ones from diet.  You are arguing they change over rapidly.  Where is the evidence of that?

 

 

Aside from the case of new adipocyte genesis; adipose cells swell and shrink depending on whether they are storing fat or releasing it.  The lipid volume in the adipocyte holds a mixture of fats -- there is no preferential in-out order, just the amount needed based on signalling.

 

Furthermore, skeletal muscle recruits FFAs from adipocytes when needed. This happens during exercise -- fat released for energy comes from stored fat in the adipocytes -- which is replaced when more fat is consumed -- there is a constant turnover of fat in the adipocytes in a non-sedentary person that is maintaining a constant lean body mass and constant bodyfat.

 

That is how fatty acid metabolism works.

[niner]

Point taken.  But probably you would help end the argument if you published some data on half life of polyfats in cell membranes.

 

This thread is a pretty interesting discussion with some great contributions by Michael Rae.  You might find it in there, or references therein.  Even if you don't, you'd probably find it worthwhile.

[pone11]

 

 

Obviously the body stores fats over time in the same composition of diet.   That's not the point at all we were arguing about.  The point is what happens to your existing fat stores, not the new ones from diet.  You are arguing they change over rapidly.  Where is the evidence of that?

 

 

Aside from the case of new adipocyte genesis; adipose cells swell and shrink depending on whether they are storing fat or releasing it.  The lipid volume in the adipocyte holds a mixture of fats -- there is no preferential in-out order, just the amount needed based on signalling.

 

Furthermore, skeletal muscle recruits FFAs from adipocytes when needed. This happens during exercise -- fat released for energy comes from stored fat in the adipocytes -- which is replaced when more fat is consumed -- there is a constant turnover of fat in the adipocytes in a non-sedentary person that is maintaining a constant lean body mass and constant bodyfat.

 

That is how fatty acid metabolism works.

 

 

Who cares about any of this?   When you change diet to either high polyfat - or zero polyfat - the existing adipose tissue doesn't contain measurable changes in polyfats for very long periods of time.   That's the direct experimental evidence that supports the half life of those adipose tissues being very long.    Everything else is pure conjecture, and in this entire conversation you haven't produced a single study that contradicts that.   Show direct biopsy measurements of fat tissues that change significantly in short periods of time from diet alone, without starvation and without extraordinary levels of exercise that change total lipids.  You haven't done that.

Edited by pone11, 18 February 2015 - 10:53 PM.

[pone11]

 

Point taken.  But probably you would help end the argument if you published some data on half life of polyfats in cell membranes.

 

This thread is a pretty interesting discussion with some great contributions by Michael Rae.  You might find it in there, or references therein.  Even if you don't, you'd probably find it worthwhile.

 

 

That was a great thread, at least until MisterE tried to turn it into part of his crusade for high carbohydrate diets and then started using all of his login IDs to start downvoting everyone in the thread who pointed out he was off topic.

 

I did address questions in that thread to the original poster, and he apparently disappeared and never came back.

 

Here is a study that partially addresses half life issues on cell membranes:

http://ajcn.nutritio.../74.full#ref-16

 

I guess we could say it depends on the type of tissue involved.   A red blood cell that turns over every 90 days is probably subject to dietary changes.  A cardiac tissue that turns over 1% a year is probably going to use a much longer half life.   Given the huge differences in turnover rates for different types of tissue, answering the half life question is probably highly non trivial.

 

Edited by pone11, 18 February 2015 - 11:01 PM.

[ambivalent]

I suspect I, like many, am more inhibited to start threads than to simply add posts to current, general ones (such as this), as we probably side against cluttering the forum with too many threads. That said, we probably lose coherency on a number of topics because they are covered fragmentally. So, anyhow, what about a thread of suggested topic discussions? A brief description of the topic wishing to be raised and if there are, say, X number of thumbs up then a new thread can be confidently created (or reasons provided summarising why it is unnecessary).

 

e.g niner recently suggested, following his and mikey's experiences, a threadcomparing different marketed brands of c60oo - but it wasn't clear there was interest in it.

 

I had a few in mind:

 

1. An associated reference thread: every time a link to a study is posted in, say, the scientific discussions thread the same link is posted in the associated reference thread along with a brief description. A thread of just references.

 

2. Something like... the criteria necessary for the dissemination of c60oo and the value of delay.Like many, I suspect,  I deliberate over what point I should consider suggesting to people within my circle of family and friends to consider taking c60. What likely value is there in delaying 6 months or up to say 10 years? When might certain developments, research occur along this timeline - eg the longecity cancer study.   

 

3. Criteria for a new poll: a thread eliciting measurements for c60 users for a new poll (and reviewing the old one) - there is a more comprehensive understanding of the expected effects now, compared to the early months over a couple of years ago when I believe the first poll/questionnaire was submitted.

 

Any thoughts?

Edited by ambivalent, 25 February 2015 - 01:08 AM.

[seescaper]

 

If it lengthens' lifespan, then it seems reasonable to assume that it must lengthen telomeres as there's a direct corelation between telomere length and lifespan. As well, there's TA-65 and its competitor TSX that lengthen telomeres. I chose to experiment with C60 rather than them, but they were considered.
 

It might not be that great of a correlation.

Conclusion: This longitudinal study of the elderly and oldest old does not support the hypothesis that telomere length is a predictor for remaining lifespan once age is controlled for.

Source

There are two DNA systems in the body, and they both age, so if you're serious about life extension you'll look into both of them. C60 may improve the health of mitochondria, but not necessarily nDNA, at least not by any presently known mechanism. As for supplements to extend telomeres, you might consider astragalus extract, which I take and at least one person here has experimented with and found it did extend telomeres.

In the post partially quoted below, GreenPower compares the effects of cycloastragenol, astragaloside IV, and astragalus extract on telomeres and finds the latter to be superior. He says--

ANALYSIS/DISCUSSION

Using Astragaloside IV had a quite large negative effect on the telomere lengths. All of the telomeres in the measured cell types decreased in length. Several of the changes were quite large and well outside the possible fault limits of the test. Based on these results and the similar results Anthony had, I would hesitate to recommend anyone from taking Astragaloside IV as a supplement.

Using Cycloastragenol had a more neutral result. The changes were within the fault limits of the test, but at least 75% of the cell types which showed any change at all showed a slight increase in telomere length. I'm still waiting to see the results Anthony got from his test. If they are posted in this thread I must have missed them.

Using "Standardised Astragalus Root Extract" for six months (+ physical training, meditation, less work, gingko biloba, orlistat and LCHF ) had a more interesting result. The median telomere length of my NK cells increased in length by a whopping 1 800 base pairs. This is an increase with 44 percent and well outside the error margin of the test!

http://www.longecity...060#entry444060

 

 

[seescaper]

Regarding telomeres:

 

The rat study was done to determine how c60 might be a poison. It was unexpected that the rats survived so long. So looking at rat telomeres was not done. However on theoretical grounds, if one presumes that maximum lifespan has at least some correlation to telomeric length, then a practical doubling of lifespan would not be reasonable without some lengthening of telomeres. This does not imply a direct effect. Further, telomeres might be short at the end when the rats eventually died, so one must look earlier in the treatment course. Remember though that the rats were left untreated for several years till they died, so had they received ongoing treatment who knows how long they might have survived? Another interesting fact is that it is postulated that lengthening telomeres will increase cancer risk, as cancer cells require long telomeres for their immortality. Yet these rats, despite the very significant likelihood of a lengthening of their telomeres, uncharacteristically did NOT get cancers. This suggests that there are mechanisms to lengthen telomeres, involving c60, that do not cause or promote cancer. This does not however mean that other methods or compounds that might lengthen telomeres also do so without increasing cancer risk. The interesting questions therefore, are: 1) Does c60 directly or indirectly promote increased telomere length? Nuclear, mitochondrial, or both?If so, is this the ultimate cause of the increased lifespan and if so, would ongoing supplementation extend lifespan indefinitely? 2) Would taking c60 concomitantly with other agents known to promote increased telomeres increase their margin of safety with respect to cancer risk? and 3) There have been many other proposed mechanisms for c60, involving DNa and mitochondrial methylation, etc. How would these proposed mechanisms affect telomere length as well?

[Logic]

Regarding telomeres:
 
The rat study was done to determine how c60 might be a poison. It was unexpected that the rats survived so long. So looking at rat telomeres was not done. However on theoretical grounds, if one presumes that maximum lifespan has at least some correlation to telomeric length, then a practical doubling of lifespan would not be reasonable without some lengthening of telomeres. This does not imply a direct effect. Further, telomeres might be short at the end when the rats eventually died, so one must look earlier in the treatment course. Remember though that the rats were left untreated for several years till they died, so had they received ongoing treatment who knows how long they might have survived? Another interesting fact is that it is postulated that lengthening telomeres will increase cancer risk, as cancer cells require long telomeres for their immortality. Yet these rats, despite the very significant likelihood of a lengthening of their telomeres, uncharacteristically did NOT get cancers. This suggests that there are mechanisms to lengthen telomeres, involving c60, that do not cause or promote cancer. This does not however mean that other methods or compounds that might lengthen telomeres also do so without increasing cancer risk. The interesting questions therefore, are: 1) Does c60 directly or indirectly promote increased telomere length? Nuclear, mitochondrial, or both?If so, is this the ultimate cause of the increased lifespan and if so, would ongoing supplementation extend lifespan indefinitely? 2) Would taking c60 concomitantly with other agents known to promote increased telomeres increase their margin of safety with respect to cancer risk? and 3) There have been many other proposed mechanisms for c60, involving DNa and mitochondrial methylation, etc. How would these proposed mechanisms affect telomere length as well?

"...Under increased oxidative stress telomerase is excluded from the nucleus and can be found within the mitochondria..."
http://www.sciencedi...531556509000862

"...While TERT maintains telomere length under standard conditions, telomeres under increased stress shorten as fast as in cells without active telomerase. This is because TERT is reversibly excluded from the nucleus under stress in a dose- and time-dependent manner..."
...Extranuclear telomerase colocalises with mitochondria. In TERT-overexpressing cells, [mitochondrial DNA] is protected, mitochondrial membrane potential is increased and mitochondrial superoxide production and cell peroxide levels are decreased, all indicating improved mitochondrial function and diminished retrograde response. We propose protection of mitochondria under mild stress as a novel function of TERT.
..."
https://www.fightagi...dysfunction.php

The Emerging Role of Telomerase Reverse Transcriptase in Mitochondrial DNA Metabolism
http://www.hindawi.c...na/2010/390791/

A new study provides insight into aging and age-related diseases by linking telomere dysfunction to a decline in mitochondrial number and function.
http://circres.ahajo.../108/8/903.full


@ the 2 disagreers:
Maybe more clicking on Google and less on the nice convenient voting system is in order.
I do hope you have the good grace to regret your ill informed impulse!?

 

(click away!)

Edited by Logic, 02 March 2015 - 11:22 PM.

[pone11]

Regarding telomeres:

 

The rat study was done to determine how c60 might be a poison. It was unexpected that the rats survived so long. So looking at rat telomeres was not done. However on theoretical grounds, if one presumes that maximum lifespan has at least some correlation to telomeric length, then a practical doubling of lifespan would not be reasonable without some lengthening of telomeres. This does not imply a direct effect. Further, telomeres might be short at the end when the rats eventually died, so one must look earlier in the treatment course. Remember though that the rats were left untreated for several years till they died, so had they received ongoing treatment who knows how long they might have survived? Another interesting fact is that it is postulated that lengthening telomeres will increase cancer risk, as cancer cells require long telomeres for their immortality. Yet these rats, despite the very significant likelihood of a lengthening of their telomeres, uncharacteristically did NOT get cancers. This suggests that there are mechanisms to lengthen telomeres, involving c60, that do not cause or promote cancer. This does not however mean that other methods or compounds that might lengthen telomeres also do so without increasing cancer risk. The interesting questions therefore, are: 1) Does c60 directly or indirectly promote increased telomere length? Nuclear, mitochondrial, or both?If so, is this the ultimate cause of the increased lifespan and if so, would ongoing supplementation extend lifespan indefinitely? 2) Would taking c60 concomitantly with other agents known to promote increased telomeres increase their margin of safety with respect to cancer risk? and 3) There have been many other proposed mechanisms for c60, involving DNa and mitochondrial methylation, etc. How would these proposed mechanisms affect telomere length as well?

 

In reference to telomeres in mice, I think the main objection would be that rodents have extremely long telomeres and rarely use those up before they die.  This idea is summarized here:

http://www.the-scien...res-in-Disease/

 

From the linked article:

"Mice are not the ideal model for telomere attrition and its effects on aging as murine telomeres are 5 to 10 times longer than human telomeres, in spite of mice having a much shorter life span. When telomerase is knocked out in mice, they live a healthy life for several generations, and even late-generation animals with very short telomeres do not display the clinical phenotypes characteristic of human telomeropathies. Telomerase-deficient mice also do not have a higher incidence of cancer, which happens only if the p53 gene also is modulated, in contrast to humans with telomerase deficiency, who are at very high risk of developing cancer."

 

Humans are the ones with telomere issues, so it seems a stretch to argue that C60 extended a rat's lifespan because of telomerase activation or telomere lengthening.

 

To contrast, rats are much more subject to oxidative stress than humans.   Humans have far more antioxidant buffers than do rodents.   Since C60 is a primary antioxidant to free radicals, you could argue that rats are much more likely to need its benefits than are humans.  That doesn't mean that the effect of C60 on human lifespan won't be measurable.  It just means that rodents might benefit from its effects on free radicals more than humans.

[sensei]

"...Under increased oxidative stress telomerase is excluded from the nucleus and can be found within the mitochondria..."
http://www.sciencedi...531556509000862

"...While TERT maintains telomere length under standard conditions, telomeres under increased stress shorten as fast as in cells without active telomerase. This is because TERT is reversibly excluded from the nucleus under stress in a dose- and time-dependent manner..."
...Extranuclear telomerase colocalises with mitochondria. In TERT-overexpressing cells, [mitochondrial DNA] is protected, mitochondrial membrane potential is increased and mitochondrial superoxide production and cell peroxide levels are decreased, all indicating improved mitochondrial function and diminished retrograde response. We propose protection of mitochondria under mild stress as a novel function of TERT.
..."
https://www.fightagi...dysfunction.php

The Emerging Role of Telomerase Reverse Transcriptase in Mitochondrial DNA Metabolism
http://www.hindawi.c...na/2010/390791/

A new study provides insight into aging and age-related diseases by linking telomere dysfunction to a decline in mitochondrial number and function.
http://circres.ahajo.../108/8/903.full


@ the 2 disagreers:
Maybe more clicking on Google and less on the nice convenient voting system is in order.
I do hope you have the good grace to regret your ill informed impulse!?

 

(click away!)

 

 

 

I posted the same info a few months ago.

 

One possible mechanism of C60OO that I propose is :  C60OO vastly decreases ROS in the cell especially near the mitochondria -- this in turn allows TERT to stay in the nucleus preventing damage and also maintaining telomere length

[Logic]

xEva:

'..."Most importantly, trusty lab mice have telomeres that are five times longer than ours but their lives are 40 times shorter. That is why the relationship between telomere length and lifespan is unclear."

A paper a was published about a year ago that showed that mice telomeres shorten 100 times faster than human http://www.cell.com/...1247(12)00263-X

If we take the data cited in this paper, telomere length is "50 kb in young ..mice, compared with15 kb in young humans", then a very crude calculation will show :

m = h(50kb/15kb)/100 = 0.033h

where m and h stand for mouse and human lifespan respectively

or that the average mouse lifespan should be 0.033 of the human. If we take human life for 80 years, then a mouse should live for 2.6 years, which seems to match the data. It appears telomeres do matter, no?..."

http://www.longecity...ndpost&p=617036

 

Reason:

"...Even before the telomeres shorten to the critical length that damages the DNA, the slow erosion in length has an effect on the cell's regulation of genes that potentially contributes to aging and the onset of disease. The [findings] required the researchers to develop new methods for mapping interactions that occur near the endcaps and to use an extensive array of methodologies to verify the impact. Specifically, the team showed that when a telomere is long, the endcap can form a loop with the chromosome that brings the telomere close to genes previously considered too far away to be regulated by telomere length. Once the telomere and the distant genes on the same chromosome are close to each other, the telomere can generally switch those genes off.

Conversely, when telomeres are short, the chromosome does not form a loop and the telomere can no longer influence whether target genes are switched on or off. The researchers were able to identify three genes whose expression patterns are altered by telomere length but believe this number is the just the tip of the iceberg. "We have developed the concept that telomere shortening could be used as a timing mechanism to respond to physiological changes in very long-lived organisms, such as humans, to optimize fitness in an age-appropriate fashion..."

http://www.longecity...ene-regulation/

 

There is some contention about the validity of the findings of the rat telomere attrition rate study, but I think that we can accept that their long telomeres don't discount previous telomere attrition theories quite as much as was thought?

Then, the fact that telomeres affect the expression of genes in an epigenetic-like way well before they become critically short looks distinctly similar to the programmed theory of aging to me!?

 

Now, if you'll excuse me, I'm of to go and pick some Purslane to go with my C60oo!

 

[pone11]

xEva:

'..."Most importantly, trusty lab mice have telomeres that are five times longer than ours but their lives are 40 times shorter. That is why the relationship between telomere length and lifespan is unclear."

A paper a was published about a year ago that showed that mice telomeres shorten 100 times faster than human http://www.cell.com/...1247(12)00263-X

If we take the data cited in this paper, telomere length is "50 kb in young ..mice, compared with15 kb in young humans", then a very crude calculation will show :

m = h(50kb/15kb)/100 = 0.033h

where m and h stand for mouse and human lifespan respectively

or that the average mouse lifespan should be 0.033 of the human. If we take human life for 80 years, then a mouse should live for 2.6 years, which seems to match the data. It appears telomeres do matter, no?..."
 

 

That Cell study is very cool and definitely changes my understanding of rat telomeres.   So, preserving length of telomeres does appear to be a primary candidate for extending lifespan.   And it is probably not crazy to then hypothesize that the rats in Baati's study saw preservation of telomere length.

 

However I would point out in that study you link from Cell, the groups with long and short telomeres did NOT have different rates of cancer.   From your study:

 

"We first determined whether the incidence of malignant cancers (lymphoma, sarcoma, and adenocarcinoma) showed any differential prevalence in mice belonging to either the higher or lower quartile of rate of increase in the percentage of short telomeres. We found a similar incidence of cancer or degenerative diseases in both cases, in spite of the fact that mice belonging to the higher quartile of rate of increase in the percentage of short telomeres showed a median age at death of 105 weeks, compared with 140 weeks in the case of mice belonging to the lower quartile (Figure S5). "

 

So the original post I was responding to - that had a long string of chained hypotheses regarding C60 -> oxidative stress -> telomere length -> cancer - still seems like it was really stretching.

[Logic]

That was Seescaper's 19th post and showed a surprising amount of insight for such a new member.
Its also posed as more of a question than a statement...

My feeling is that if telomeres stay long cancer is kept at bay.
Its when they get short (which affects neighbouring DNA) and we start getting 'glitches in the program' and the cell is already pre/senescent/cancerous that it is dangerous to activate telomerase.

C60oo might help keep telomeres long as well as prevent mitochondria from being 'switched off' in pre/cancerous cells.

(I think it wise to do an anti cancer stack similar to the one on AntiAgingFirewalls' blog site (+ C60oo) for a good while before a telomerase activation stack to clean out such cells, so that only healthy (hopefully) cells are left when telomerase activation is done.

Also upregulation of Phagy.)

The epigenetic-like gene regulation by long telomeres probably plays a role in all this, but I don't want to hazard a guess as to how?

I think C60oo may keep telomerase in the nucleus where they can increase telomere length when on a telomerase activation stack may help or even be synergistic with activators.
It may well be that C60oo dramatically slows, or even reverses, telomere attrition as well as protects mitochondrial DNA etc.

(I saw dramatic results from C60oo - Telomerase activation combo stack)

It may also slow lipid peroxidation etc.
It may be all or none of these things which doubled the lifespan of Baati's rats. Probably somewhere in-between?

At this point there just isnt enough research to be sure and all semi informed/educated guesses are and have been welcome at the debating table IMHO?

[pleb]

I think the original theory proposed two years ago is probably nearer the actual way it works.
It mops up ROS by electron transfer. It's known that 70 per cent of damage to our cells and 80 per cent of damage to our telomeres are caused by ROS. as its an inorganic molecule it can't work the way some suggest it's not a hormone in any sense so is unlikely to be able to switch on or off any genes.
but by mopping up ROS and slowing down damage the cells live longer as the attrition on telomeres is slowed down giving a longer period before reaching the Hayflick limit. and also fewer pre cancerous cells are formed. enough that the bodies repair mechanism is not overwhelmed as is usual in later life.

[Logic]

I don't see it as a case of C60oo signalling the Telomerase to stay in the nucleus Pleb; it works as you say, and because there is 'no' oxidative stress in the mitochondria, telomerase stays in the nucleus by whatever means it normally would under good/young conditions.

 

If you then increase telomerase you have more where you want it.

If you keep them long enough to be able to affect the genome in an epigenetic-like manner, you may just be able to overcome 'the Programmed Theory of Aging' and C60oo may just do that if started early enough.

 

ie: Taking the ROS produced by mitochondrial respiration 'out of the equation' would probably have all sorts of positive downstream effects.

 

If we can take an educated guess at what they may be and find ways of to further optimise these processes, we might well get a bit of  rejuvenation happening.

 

I for one found that the telomerase activation stack I had taken before, suddenly seemed to work incredibly well when I added C60oo.

I was 44 at the time and had university students smiling at me.!

 

 

[pleb]

I don't think it upregulates telomerase at all. It just cuts down the amount of damage to our telomeres so the cell has a longer life and the Hayflick limit is extended. It can only do things as a side effect simply because it is inorganic.
as for the students.you vain bugger. lol

[sensei]

I don't think it upregulates telomerase at all. It just cuts down the amount of damage to our telomeres so the cell has a longer life and the Hayflick limit is extended. It can only do things as a side effect simply because it is inorganic.
as for the students.you vain bugger. lol

 

It does effectively upregulate telomerase in the nucleus.  TERT has been definitively shown to migrate OUT of the nucleus -- to the mitochondria when the cell is under oxidative stress.

 

The migration of TERT out of the nucleus effectively downregulates the expression of telomerase within the nucleus.

 

Preventing the migration of TERT to the mitochonria (this is obviously a survival mechanism as the telomerase upregulation in the mitochondria protect the mitochondria from the ROS -- thereby preventing cellular senescence caused by mitochondrial damage) means that the TERT is available in the nucleus to induce telomerase expression.

 

C60OO provides a plausible mechanism by which ROS are neutralized lowering the oxidative stress on the cell -- likely keeping whatever cellular mechanism that causes the TERT to migrate out of the nucleus from happening.

 

Therefore TERT is expressed in the nucleus at higher levels than would otherwise be physiologically normal under metabolic ROS induced stress. -- effective upregulation of nuclear telomerase (where it can do its job of preventing damage to Nuclear DNA as well as maintaining or lengthening telomeres).

[pleb]

It's still only a side effect not a direct effect. The telomerase is not upregulated it is just staying in the same place rather than being moved or more produced.

[Logic]

It's still only a side effect not a direct effect. The telomerase is not upregulated it is just staying in the same place rather than being moved or more produced.

True. but as side effects go; I'll take it!

I actually see both your points of view.
You are saying its not actively increasing the total amount of telomerase in the cell just causing more to stay in the nucleus where its needed.
and
Sensei is saying that be keeping it in the nucleus where its needed you could argue that it is in fact actively increasing Telomerase activity.

Two different ways of seeing the same thing really.
I'm just happy to have got my point across!

Edited by Logic, 03 March 2015 - 09:26 PM.