Herbie
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I have herniated discs and recently tried dhea with dmso but I got extremely sick from dmso so will try tocopherals now
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Human Age Reversed By 2.5 Years By Combo Of Metformin, DHEA And GH
- Thread starter Goobz
- Start date
Interesting discussion guys.
For me, what was interesting was the results - age reversal as measured via methylation clocks and thymus regeneration... in humans! This is pretty big. Im less interested in the specific intervention they used.
And for that reason @haidut I think it's a pretty big leap to conclude those other practical interventions you mentioned would be better. What you posted seem to be animal studies of basic physiological mechanisms. This would need to be translated into interventional ones. And yeah... they're done on animals! They may or may not have similar effects in humans. Really nothing like the level of evidence from the study here, which was done in humans, and measuring methylation patterns before and after a specific intervention.
Not to say thyroid progesterone etc won't be a better alternative - it may well be. But we can't conclude that from those animal studies IMO.
And I guess I wouldn't really say this is "mainstream" science at all. This is the result of a man who has a specific interest in thymus regeneration, in California, and the study involves general anti-aging enthusiasts. And critically what they were doing personally in their own lives was working, both before and after the study, as measured by the methylation clocks at least.
Personally I'd be surprised if the HGH was the important ingredient here. Mitteldorf's take makes sense to me, that it's just as likely the zinc and vitamin D. But hopefully more research like this gets done, and we find out.
For me, what was interesting was the results - age reversal as measured via methylation clocks and thymus regeneration... in humans! This is pretty big. Im less interested in the specific intervention they used.
And for that reason @haidut I think it's a pretty big leap to conclude those other practical interventions you mentioned would be better. What you posted seem to be animal studies of basic physiological mechanisms. This would need to be translated into interventional ones. And yeah... they're done on animals! They may or may not have similar effects in humans. Really nothing like the level of evidence from the study here, which was done in humans, and measuring methylation patterns before and after a specific intervention.
Not to say thyroid progesterone etc won't be a better alternative - it may well be. But we can't conclude that from those animal studies IMO.
And I guess I wouldn't really say this is "mainstream" science at all. This is the result of a man who has a specific interest in thymus regeneration, in California, and the study involves general anti-aging enthusiasts. And critically what they were doing personally in their own lives was working, both before and after the study, as measured by the methylation clocks at least.
Personally I'd be surprised if the HGH was the important ingredient here. Mitteldorf's take makes sense to me, that it's just as likely the zinc and vitamin D. But hopefully more research like this gets done, and we find out.
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Sativa
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Except for DHEA, It all seems a bit dumb! Ideally, people would familiarise themselves with some of the 'forum basics'/Ray Peat articles before making posts, lol
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Are you referring to me? Are you saying that because this study seems to go against the forum basics / ray peat articles you mention, then it shouldn’t be posted? *scratches head*
I mean really, do you think Ray Peats articles are a better source of scientific fact than.... the latest published science? If you read science that contradicts Ray Peat, do you assume it must be wrong / poorly designed?
For psychological reasons I 100% understand why people turn to a guru to interpret complex things for them. That’s the way humans are wired.
But.... there is absolutely nothing scientific about that approach. It’s far more akin to religion.
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Terma
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lol at the religion bit
Here's a clue:
In a normal day (by most people's standards), the GH spike is released several hours after the last dinner [biggest meal of the day]. This means specifically: nighttime GH spike evolved [depending on whether people did this in prehistoric times] mostly under the influence of a bioavailable supply of amino acids - and quite possibly other things. This is why its IGF-1 production is amino acid-dependent. This IGF-1 is the real throttle on nighttime growth. This isn't really news.
Meaning, it's likely you can say that at least some of the problems caused by GH are due to nutrient insufficiency and could be proportional to the time between the GH release and the time the appropriate nutrients [and hormones] are introduced.
I don't fear GH because I've been eating high protein for 5+ years trying to repair my joints [plus the other hormones + etc.]. They always worsen when I lower my protein intake. This is why I cannot do amino acid restriction - gave up on that. If there is a hormone or process that can increase the amount of protein [that I consume] that is utilized for skeletal repair, that's what I have to do [i.e. localized IGF-1 and mTorC1, GH because of possible GH-specific effects, etc.].
This is just to say again that GH is not meant to work alone [remember also the methylation cycle is likely a big player here; noteworthy being the effects of spermidine on autophagy, etc.] and it is that nighttime peak's timing in the circadian rhythm that really matters [to me, anyway].
Here's a clue:
In a normal day (by most people's standards), the GH spike is released several hours after the last dinner [biggest meal of the day]. This means specifically: nighttime GH spike evolved [depending on whether people did this in prehistoric times] mostly under the influence of a bioavailable supply of amino acids - and quite possibly other things. This is why its IGF-1 production is amino acid-dependent. This IGF-1 is the real throttle on nighttime growth. This isn't really news.
Meaning, it's likely you can say that at least some of the problems caused by GH are due to nutrient insufficiency and could be proportional to the time between the GH release and the time the appropriate nutrients [and hormones] are introduced.
I don't fear GH because I've been eating high protein for 5+ years trying to repair my joints [plus the other hormones + etc.]. They always worsen when I lower my protein intake. This is why I cannot do amino acid restriction - gave up on that. If there is a hormone or process that can increase the amount of protein [that I consume] that is utilized for skeletal repair, that's what I have to do [i.e. localized IGF-1 and mTorC1, GH because of possible GH-specific effects, etc.].
This is just to say again that GH is not meant to work alone [remember also the methylation cycle is likely a big player here; noteworthy being the effects of spermidine on autophagy, etc.] and it is that nighttime peak's timing in the circadian rhythm that really matters [to me, anyway].
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Sativa
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No.
And no, that just sounds like an assumption on your behalf.
I was probably just stating the obvious in-case anyone assumed that metaformin/GH were desirable for longevity. It would be irresponsible for someone not to point out these issues.
LeeLemonoil
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Towards natural mimetics of metformin and rapamycin
Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals—safer, naturally-occurring compounds—that mimic the anti-aging effects of metformin and rapamycin without adverse effects. We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network-based Cellular Signatures (LINCS) dataset to map the gene- and pathway-level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds. We then predicted the safety of each compound with an ensemble of deep neural network classifiers. The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferin A (both). Four relatively unexplored compounds also scored well with rapamycin. This work revealed promising candidates for future experimental validation while demonstrating the applications of powerful screening methods for this and similar endeavors.
Aging is now at the forefront of major challenges faced globally, creating an immediate need for safe, widescale interventions to reduce the burden of chronic disease and extend human healthspan. Metformin and rapamycin are two FDA-approved mTOR inhibitors proposed for this purpose, exhibiting significant anti-cancer and anti-aging properties beyond their current clinical applications. However, each faces issues with approval for off-label, prophylactic use due to adverse effects. Here, we initiate an effort to identify nutraceuticals—safer, naturally-occurring compounds—that mimic the anti-aging effects of metformin and rapamycin without adverse effects. We applied several bioinformatic approaches and deep learning methods to the Library of Integrated Network-based Cellular Signatures (LINCS) dataset to map the gene- and pathway-level signatures of metformin and rapamycin and screen for matches among over 800 natural compounds. We then predicted the safety of each compound with an ensemble of deep neural network classifiers. The analysis revealed many novel candidate metformin and rapamycin mimetics, including allantoin and ginsenoside (metformin), epigallocatechin gallate and isoliquiritigenin (rapamycin), and withaferin A (both). Four relatively unexplored compounds also scored well with rapamycin. This work revealed promising candidates for future experimental validation while demonstrating the applications of powerful screening methods for this and similar endeavors.
Sativa
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Agmatine shares the properties of Ketamine's anti depressant effects, via the mTOR AMPA pathway, = neurogenesis. They activate mTOR.
Curiousman
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I wonder if the DHEA is playing one of the critical roles. I think this study...
A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention
... was posted on this forum before (DHEA helping in addiction) but what interested me was the specifics - the cocaine addicts had particular methylation patterns in their brain and T cells, and these changes were reversed by DHEA treatment (at a rather huge dose of 100mg though). The 2.5-year-age-reversal-study was using a DNA methylation clock to track their aging changes. So potentially its two studies showing DHEA can reverse harmful patterns of methylation.
Whats also interesting to me is how niacin/niacinamide/nad+ is also a treatment for both addiction and in theory, aging, and also has strong effects on methylation.
A DNA Methylation Signature of Addiction in T Cells and Its Reversal With DHEA Intervention
... was posted on this forum before (DHEA helping in addiction) but what interested me was the specifics - the cocaine addicts had particular methylation patterns in their brain and T cells, and these changes were reversed by DHEA treatment (at a rather huge dose of 100mg though). The 2.5-year-age-reversal-study was using a DNA methylation clock to track their aging changes. So potentially its two studies showing DHEA can reverse harmful patterns of methylation.
Whats also interesting to me is how niacin/niacinamide/nad+ is also a treatment for both addiction and in theory, aging, and also has strong effects on methylation.
LeeLemonoil
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Thanks @Goobz
Terma
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Very interesting. If DHEA pans out, it might be the ultimate molecule to take with a methylation protocol, to help ensure proper utilization of the methyl (although this seems to say nothing of histones). The combo with GH makes sense in this respect since GH is a methylation cycle promoter. GH makes resources available while DHEA and IGF-1 put them to use in the right places or prevent their misuse. The hormonal redistribution of resources between tissues at nighttime should be a key to healing, albeit the devil is in the details (tissue-specific actions; other hormones probably have to be involved too). AMPK and NAD should help implement this. Alternatively DHEA might simply make even more sense to take with high-protein meals in general, which was somewhat already a given given the IGF-1. That might evolve into an argument for avoiding large protein intake without cholesterol or any of the hormone-synthesizing cofactors, in other words tons of lean meats and powders. I slowly drift away from the notion of "good" and "bad" amino acids, rather looking for the factors that promote their optimal tissue distribution and usage, since they are all essential somewhere and in healing.
LeeLemonoil
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This sounds sensible, @Terma.
I personally think the life-extenders or death-defiers/Sith Lords are deluding themselves with thinking that immortality can be achieved. At least not in the time frame the prominent exponents of them think (50-100 years from now)
But still findings and trials like this might help us attain longer health-span than longer life span or at the very least help understanding pathology better. And you are right. Glycine here, Methione there... thi good, that bad.
No. Context matters. Under certain conditions, circumstances, depending on time and dose, substances are either more „beneficial“ or rather harmful. And then there is the limit of foresight - how would beneficial effects pan out in the long run in an ultracomplex, chaotic and entropic system.
That’s where intuition and body-feeling comes into play which naturally also only gets you so far and depends on a plethora of things.
I personally think the life-extenders or death-defiers/Sith Lords are deluding themselves with thinking that immortality can be achieved. At least not in the time frame the prominent exponents of them think (50-100 years from now)
But still findings and trials like this might help us attain longer health-span than longer life span or at the very least help understanding pathology better. And you are right. Glycine here, Methione there... thi good, that bad.
No. Context matters. Under certain conditions, circumstances, depending on time and dose, substances are either more „beneficial“ or rather harmful. And then there is the limit of foresight - how would beneficial effects pan out in the long run in an ultracomplex, chaotic and entropic system.
That’s where intuition and body-feeling comes into play which naturally also only gets you so far and depends on a plethora of things.
Terma
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Life is a constant battle against entropy, isn't it. I won't see that within my lifetime, let's say.
Some people can make it to old age on crap diets. So there is obviously major hormonal, metabolic, ROS-handling and environmental stress factors. That's why some cats make it to advanced years on diets whose equivalents would be cruel and unusual punishment to feed to humans. An organism should thrive on combined high NAD+ and NADPH levels, strong circadian rhythm, low inflammation, and low-stress environment all together... Either those insults (PUFA FFAs, amino acids) don't get released/triggered much, they are handled by the various systems, they are redirected or prevented from nefarious pathways, their negative side-effects can be healed from at a sufficient rate, or better yet the combination of these things (their proper handling) may even leave a net positive effect of the amino acid or other molecule on the organism beyond survival even in excess? High-protein diets have a place in health. I don't know how long we can live but I can see we are far from our potential and it will be essential to identify exactly where this happens and how this can be achieved.
Anyway maybe haidut was right the original study authors probably shouldn't be idolized or whatever level of depravity floats your boat. I'm not the best judge of character :P. But it's still worthwhile information to know GH wouldn't destroy your thymus as long as DHEA is there. And if you assume its conversion, it and estrogen wouldn't block DHEA's (or whatever else is going on there) effects on DNA methylation. That's actually quite encouraging. Unfortunately progesterone just does not cut it for me.
Some people can make it to old age on crap diets. So there is obviously major hormonal, metabolic, ROS-handling and environmental stress factors. That's why some cats make it to advanced years on diets whose equivalents would be cruel and unusual punishment to feed to humans. An organism should thrive on combined high NAD+ and NADPH levels, strong circadian rhythm, low inflammation, and low-stress environment all together... Either those insults (PUFA FFAs, amino acids) don't get released/triggered much, they are handled by the various systems, they are redirected or prevented from nefarious pathways, their negative side-effects can be healed from at a sufficient rate, or better yet the combination of these things (their proper handling) may even leave a net positive effect of the amino acid or other molecule on the organism beyond survival even in excess? High-protein diets have a place in health. I don't know how long we can live but I can see we are far from our potential and it will be essential to identify exactly where this happens and how this can be achieved.
Anyway maybe haidut was right the original study authors probably shouldn't be idolized or whatever level of depravity floats your boat. I'm not the best judge of character :P. But it's still worthwhile information to know GH wouldn't destroy your thymus as long as DHEA is there. And if you assume its conversion, it and estrogen wouldn't block DHEA's (or whatever else is going on there) effects on DNA methylation. That's actually quite encouraging. Unfortunately progesterone just does not cut it for me.
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Ruslan Andreev
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does anyone know what exactly the drugs are and if they work, combined ?
Veritas IV
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@LeeLemonoil , pardon me for bumping an old post, but am going to plant the following link in this thread.
Unauthorized Science | Josh Mitteldorf | Substack
Radical Empiricism at unauthorizedScience.org. Click to read Unauthorized Science, by Josh Mitteldorf, a Substack publication with thousands of subscribers.
mitteldorf.substack.com
Apparently Josh Mitteldorf has a substack whose content goes beyond aging/rejuvenation and into other neglected aspects of science, even politics. Can't wait for some downtime to sink my teeth into that one.
Edit: i've posted Josh Mitteldorf info elsewhere in this forum but misspelled his last name as Mittledorf, meaning it won't turn up as a result in a forum search.
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LeeLemonoil
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Im aware of that but never read into it. I think some time ago he said a lot of non mainstream things in politics field and consequently was character assassinated and they tried to delegitimize him in his original field of expertise too@LeeLemonoil , pardon me for bumping an old post, but am going to plant the following link in this thread.
Unauthorized Science | Josh Mitteldorf | Substack
Radical Empiricism at unauthorizedScience.org. Click to read Unauthorized Science, by Josh Mitteldorf, a Substack publication with thousands of subscribers.
Apparently Josh Mitteldorf has a substack whose content goes beyond aging/rejuvenation and into other neglected aspects of science, even politics. Can't wait for some downtime to sink my teeth into that one.
Edit: i've posted Josh Mitteldorf info elsewhere in this forum but misspelled his last name as Mittledorf, meaning it won't turn up as a result in a forum search.
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