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Alpha-Ketoglutarate as an Anti-Aging, Anti-Frailty Compound

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#121 yz69

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Posted 28 February 2021 - 06:10 PM

Reversing the methylation patterns does nothing for reversing the accumulated damage. 

 

 

How do you make such conclusion? Do you have any source to support this conclusion?


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#122 Guest

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Posted 28 February 2021 - 06:27 PM

How do you make such conclusion? Do you have any source to support this conclusion?

 

That's not how science works. You can't prove a negative.

 

But you can prove a positive - i.e. demonstrating, that reversing methylation is reversing your accumulation of damaged mitochondria and breaking up cross-links or lipofuscin (or cardiovascular plaque etc.).

 

 

Those studies, to my knowledge, do not exist (maybe there are some very recent ones).

 

 

To my knowledge there are studies in twins, that show lower mortality over time in association to certain methylation patterns. So there might be an effect on the accumulation of future damage. But to my knowledge there are no studies demonstrating reversal of the damages, that in summary constitute the aging phenotype.


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#123 yz69

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Posted 28 February 2021 - 07:20 PM

Would improving kidney function (better eGFR) be considered some sort of "reversing damage", according to Fahy's TRIIM paper, the participants saw increased eGFR after trial as well as lowered DNAm age.


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#124 Guest

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Posted 28 February 2021 - 07:26 PM

I would also suggest to read the Wikipedia article about this topic:

 

https://en.wikipedia...pigenetic_clock

 

....making clear, that it is very much uncertain, what methylation clocks actually mean in terms of interventions for biological age.

 

 

And ask yourself:

 

The human body lacks the enzymes, to break up the lipofuscin, that accumulates in lysosomes. How is reversing methylation patterns going to change that, to make autophagy function again?

 

Plaque are forming in your vascular system, because immune cells can't digest the fatty deposits - forming foam cells instead. How is reversing methylation patterns going to reverse that?

 

Cross-linked proteins/AGE are forming between cells, disturbing normal tissue function. Once established the human body has no effective mechanism to remove them. How is reversing methylation patterns going to change that, if even young people can't do it?

 

etc. 

 

etc.


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#125 yz69

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Posted 28 February 2021 - 08:02 PM

You are saying some "damages" are hard to reverse. But there are some "damages" can still be reversed, which is not bad, right? At least according to Fayh, Kennedy, they are making some progress.


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#126 TMNMK

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Posted 28 February 2021 - 08:09 PM

@TMNMK:

 

EVERY Vitamin is useful. The point was, that overdosing on Vitamin A is a problem. The in-vitro studies you are quoting don't change that.

 

Vitamin A is fat-soluble vitamin. It is in circulation much longer than water soluble Vitamins. Rejuvant contains 100% of the RDA for Vitamin A. We have studies in living humans (not mice cells in a dish) demonstrating long term liver damage, if you take about 10 times the RDA of Vitamin A for a prolonged duration. And if you want to have the mice effects you need to take more than the single serving of Rejuvant on their label (the mice consumed up to 30 times the amount, scaled for humans).

 

 

Yes I should have been more clear, I do agree with  your point entirely about that, mine was more from a general sense of one reason that they may be including vit. A in that product generally speaking.



#127 TMNMK

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Posted 28 February 2021 - 08:36 PM

 

To my knowledge there are studies in twins, that show lower mortality over time in association to certain methylation patterns. So there might be an effect on the accumulation of future damage. But to my knowledge there are no studies demonstrating reversal of the damages, that in summary constitute the aging phenotype.

 

There are appearing some demonstrations under very specific circumstances that suggest such things may be possible. Will studies such as the following be repeatable and further will they generalize? We won't know for some time yet.

 

These studies remind me of the development of immune checkpoint inhibitors; how quickly that changed the tone of tens of thousands of conversations had between oncologists and their patients. You can see it in their eyes, they smile much more often! A mere 5-10 years ago those conversations were often much darker.

 

https://www.biorxiv....710210.full.pdf

 

 

https://www.biorxiv....426786.full.pdf

 

 

https://www.research...nd_rejuvenation


Edited by TMNMK, 28 February 2021 - 08:38 PM.

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#128 QuestforLife

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Posted 28 February 2021 - 08:55 PM


And ask yourself:

The human body lacks the enzymes, to break up the lipofuscin, that accumulates in lysosomes. How is reversing methylation patterns going to change that, to make autophagy function again?

Plaque are forming in your vascular system, because immune cells can't digest the fatty deposits - forming foam cells instead. How is reversing methylation patterns going to reverse that?

Cross-linked proteins/AGE are forming between cells, disturbing normal tissue function. Once established the human body has no effective mechanism to remove them. How is reversing methylation patterns going to change that, if even young people can't do it?

etc.

etc.


Thanks but I've already read Aubrey's book.

I remind you that metabolic waste products being the root cause of aging is a theory.

That is not to say we shouldn't investigate such a theory. But let's not dismiss epigenetic changes out of hand.
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#129 TMNMK

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Posted 01 March 2021 - 07:53 AM

Well as usual people get to talking here and I wind up blowing an entire late Sunday evening. Relevant to some of what was being discussed here, so if you haven't seen it, it is a nice one: https://www.foundmyf...n=steve_horvath

 

Minutes 47+ gets pretty neat!

 



#130 Guest

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Posted 01 March 2021 - 01:04 PM

Thanks but I've already read Aubrey's book.

I remind you that metabolic waste products being the root cause of aging is a theory.

That is not to say we shouldn't investigate such a theory. But let's not dismiss epigenetic changes out of hand.

 

You are right, that Aubrey's propositions are a theory - but this does not mean, that they are "theoretical" in a sense, that they are speculative.

 

He is specifically looking at, what specific cellular/tissue changes are causing the aging-associated pathologies and death - and then tracing them back to a number of common root mechanisms. E.g. there is not much to debate about, that aging associated cardiovascular disease (stroke, heart attack, declining blood supply) is caused by ruptured plaque (that is foam cells) and stiffening of arteries (that is cross links).

 

 

Epigenetic changes as measured by methylation clocks (and their reversal) might tie in into some of the damages - e.g. stem cell exhaustion or senescent cells. So there is possibly some room for a role here, I agree. But which methylation changes you need to create, that are reversing those components of the "damage theory of aging" is still an open question and should not be concluded from the broad test that are currently commercially offered.



#131 QuestforLife

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Posted 01 March 2021 - 02:35 PM

You are right, that Aubrey's propositions are a theory - but this does not mean, that they are "theoretical" in a sense, that they are speculative.

 

He is specifically looking at, what specific cellular/tissue changes are causing the aging-associated pathologies and death - and then tracing them back to a number of common root mechanisms. E.g. there is not much to debate about, that aging associated cardiovascular disease (stroke, heart attack, declining blood supply) is caused by ruptured plaque (that is foam cells) and stiffening of arteries (that is cross links).

 

 

Epigenetic changes as measured by methylation clocks (and their reversal) might tie in into some of the damages - e.g. stem cell exhaustion or senescent cells. So there is possibly some room for a role here, I agree. But which methylation changes you need to create, that are reversing those components of the "damage theory of aging" is still an open question and should not be concluded from the broad test that are currently commercially offered.

 

I have been a supporter of SENS for many years, with a small direct debit per month contribution. I do think that ultimately we will need to deal with various ingestible metabolic products and that this should be done in tandem with other exciting treatments discussed here and elsewhere. It is not clear to me which treatments will have the greatest benefit, or if as Aubrey claims, nothing will work until everything works.

 

I do think it is a mistake to list various things that change with age and assume they are the cause of aging (whether these are the build up of waste products, or epigenetic changes). We just don't know.

 

SENS was invented 20 years ago. MitoSENS is looking shaky now; WILT never looked promising; extracellular and intracellular aggregates still look a good bet. Nothing about epigenetics was known. It is probably not the place here to discuss this further.

 

I wholeheartedly agree with you on the problems with epigenetic clocks. It seems unlikely that the changes Horvath sees for example, are the cause of aging; if they were we wouldn't find them in so many surviving old people. But some subset of those epigenetic changes probably do play a causal role in some fraction of the deterioration we see with age.  Time and testing will tell.


Edited by QuestforLife, 01 March 2021 - 02:37 PM.

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#132 platypus

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Posted 02 March 2021 - 02:42 PM

Is AAKG equally good as CaAKG and ohers, and what should be a conservative starting dosage?



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#133 aribadabar

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Posted 02 March 2021 - 02:57 PM

Is AAKG equally good as CaAKG and ohers, and what should be a conservative starting dosage?


It is close enough. 3g of AAKG fits your requirement.





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