Human Age Reversed By 2.5 Years By Combo Of Metformin, DHEA And GH

[Goobz]

Just saw this then. Pretty interesting stuff

First hint that body’s ‘biological age’ can be reversed

 

[Terma]

Thanks that's beautiful man

Scientists like this are why I read this ***t

https://www.gwern.net/docs/longevity/2019-fahy.pdf

[I'm about to read it lol]

[Maybe a little later...]

Sugar funnels into my 2L bottle... like the sands of time.

 

[Goobz]

Thanks that's beautiful man

Scientists like this are why I read this ***t

https://www.gwern.net/docs/longevity/2019-fahy.pdf

[I'm about to read it lol]

[Maybe a little later...]

Sugar funnels into my 2L bottle... like the sands of time.

Let us know if you have any thoughts!

I only read over it quickly, but I found it interesting, the link between thymus regeneration and aging. The point of the study was to regenerate the thymus, testing the biological age via DNA methylation clock was an afterthought.

 

[LeeLemonoil]

So now they finally published the data.

Thymus rejuvenation has been a main focus of the life-extenders for quite some time. Her Josh Mitteldorf discussed the results:

https://joshmitteldorf.scienceblog....results-is-it-hgh-or-something-else/#comments

 

[LeeLemonoil]

The approach with high dose DHEA and Metformin seems risky if all that’s „needed“ is increased HGH but offsetting of its insulin-resistance needs to be achieved simultaneously.

Maybe the compiled knowledge of the RPF could come up with a better stack. Note that thymus-degeneration seems to go hand in hand with androgen-homeostasis. This life extension comes at a price

 

[Goobz]

The approach with high dose DHEA and Metformin seems risky if all that’s „needed“ is increased HGH but offsetting of its insulin-resistance needs to be achieved simultaneously.

Maybe the compiled knowledge of the RPF could come up with a better stack. Note that thymus-degeneration seems to go hand in hand with androgen-homeostasis. This life extension comes at a price

Thanks for that link - i like that guy's thinking.

I like his little takeaway - it may well not be about HGH at all.

There is no known mechanism whereby HGH is expected to affect the methylation profile. This is not to say that it does not do so, but it is just as viable to think that the combination of vitamin D and Zn is affecting methylation age.

High blood levels of vitamin D and zinc are known to be correlated with lower all-cause mortality and longer life expectancy. Metformin is being investigated in its own right as an anti-aging drug. DHEA has been promoted as an anti-aging supplement for decades, though existing studies indicate DHEA does not increase lifespan in mice. The principal effect of HGH is to increase the hormone IGF1, and DHEA also does this, far more cheaply and over-the-counter, but to a much smaller extent.

HGH is both expensive and theoretically suspect for long-term use. Elevated levels of IGF1 are known to decrease lifespan in rodents; dwarf mice and dwarf humans without IGF1 receptors live longer, healthier lives [ref]. Readers looking to make immediate changes to their personal stack based on the results of this experiment might try the four cheap and proven ingredients, leaving out the HGH for now.

 

[LeeLemonoil]

Yep, however it is turned or interpreted, i would never touch that combo of Dhea 50mg, Metformin and HGH. If that’s the combined wisdom of prolific life-extenders than let them have fun.

 

[Goobz]

Yep, however it is turned or interpreted, i would never touch that combo of Dhea 50mg, Metformin and HGH. If that’s the combined wisdom of prolific life-extenders than let them have fun.

Yep I agree.

Though I was impressed by this part, too:

• At the start of the test, the average epigenetic age of the group was already well below average chronological age. This is presumably because the subjects tended to be highly-motivated anti-aging enthusiasts. Whatever they were doing before the TRIIM study was already working well. By the Levine Clock, they were 17 years (!) younger than their chronological age, and by the GrimAge clock they were 2 years younger.

 

[LeeLemonoil]

Yes, lifespan-variances are to be exploited, I think that’s what we health-oriebtated peaters do too.
But they still can’t know if that’s legit measurement or if what they think makes them chronologically younger will have other disadvantages that might nullify that effect longterm.
I doubt humans will ever attain immortality, I think there are unconquerable death-switches in our philology - literaly

 

[ddjd]

Sylvester Stallone used and still uses a ***t load of GH and he's doing pretty good

 

[Herbie]

Sylvester Stallone used and still uses a ***t load of GH and he's doing pretty good

Fake hair, unatural looking teeth, make up.

 

[ddjd]

Fake hair, unatural looking teeth, make up.

owning and starring in movie franchises worth hundreds of millions of dollars, in your 70s. yeah terrible performance. he probably looks better than you do now

 

[reality]

Is it right to say anything that increases methylation can speed up aging? Or slow down?

 

[haidut]

The approach with high dose DHEA and Metformin seems risky if all that’s „needed“ is increased HGH but offsetting of its insulin-resistance needs to be achieved simultaneously.

Maybe the compiled knowledge of the RPF could come up with a better stack. Note that thymus-degeneration seems to go hand in hand with androgen-homeostasis. This life extension comes at a price

This! Thanks for bringing it up. This study, while welcome for finally showing that there is nothing irreversible about aging and aging is likely not much different than disease and should be treated as such, is designed extremely poorly. The authors themselves say that growth hormone is known to cause diabetes so that's why they added the DHEA - i.e. to offset the negative effects of HGH. However, such high DHEA dose has negative effects of its own, including conversion into estrogen. There are much simpler and safer approaches to regenerating thymus. Namely, thyroid hormone and/or blocking estrogen/cortisol. The latter approach immediately shows why this study above was of very poor design. If blocking estrogen regenerates thymus then taking high dose DHEA does not seem like a very wise idea. I am constantly amazed at just how idiotic mainstream research is. It is astonishing that any progress is being made at all and corroborates the claims of Nobel laureate Luc Montagnier that progress in today's medicine is akin to randomly colliding 15 billiard balls and waiting for them to arrange themselves spontaneously into the familiar triangle at he beginning of the game.
Oh, and needless to say, the links below once again corroborate Peat's views. Hey, @charlie, do you have that emoticon about Peat being right again?

So, what does that mean in terms of practical interventions? Well, taking T3 is one an obvious intervention given the studies below. However, it is a prescription drug and many people struggle with finding the right dosage. An OTC approach that both mimics the study in the OP and actually goes above and beyond would be to use a progesterone/DHEA combination. Progesterone (P4) is the most potent endogenous antagonist of both estrogen and cortisol, and DHEA is also a glucocorticoid antagonist. So, a ratio of 1:1 up to 10:1 for P4HEA can likely replicate the anti-aging effects much more safely and likely exceed them, because unlike the OP study which did not use any estrogen blockers to prevent DHEA from wreaking havoc, adding P4 to DHEA would have an anti-estrogenic effect. In addition, progesterone has pro-thyroid effects and may mimic to a degree the thymotropic effects of T3 mentioned in the studies below.

Reducing Estrogen Synthesis Regenerates Thymus Destroyed By Aging
Pleiotropic influence of triiodothyronine on thymus physiology. - PubMed - NCBI
"...It is well demonstrated that the thymus gland is under neuroendocrine control. Thymic endocrine function can be modulated by a variety of hormones including those secreted by the thyroid gland. This prompted us to investigate putative influences of T3 in further aspects of thymus physiology. We showed that T3-treated animals exhibited an increase in thymus weight, cellularity and cycling cells. Moreover, Thy1+ thymocytes as well as CD4-CD8 defined subsets were augmented in absolute numbers, whereas PgP.1+ cells increased in both absolute and percentage values. In parallel, the total numbers of thymic nurse cells were also increased. Regarding the expression of extracellular matrix components (ECM) by microenvironmental cells, we observed an enhancement in the intrathymic ECM upon T3 in vivo treatment. Similar effects were found in vitro by treating a thymic epithelial cell line or thymic nurse cell-derived epithelial cultures with T3. This treatment also increased the expression of ECM receptors by thymic epithelial cultures. Interestingly, an enhancement in thymocyte/thymic epithelial cell adhesion ratio was observed after T3 treatment of epithelial cells. Our data suggest that T3 exerts a pleiotropic effect upon thymus physiology, stimulating thymocyte differentiation, not only by modulating epithelial cell hormonal secretion but also their production of ECM proteins and respective receptors."
Thyroid function modulates thymic endocrine activity. - PubMed - NCBI
Thyroid-thymus interactions during development and aging. - PubMed - NCBI

 

[charlie]

Hey, @charlie, do you have that emoticon about Peat being right again?

Yes sir!

 

[Terma]

You could be right about enhanced conversion into estrogen/estrone depending on circumstances, haidut, but GH is a nighttime healing hormone. It replaces cortisol and permits the liver methylation cycle. It works together with thyroid and DHEA. In my opinion he is wrong about that hormone insofar as we evolved an importance for it in the circadian rhythm. He sees nighttime as a stressor to be counteracted in every way and in his mind nighttime food restriction should be abolished for our ultimate benefit - which someday might be the optimal solution - but that is unrealistic for our current knowledge - he is really thinking what we could do with the knowledge we'd have 25-100 years from now or something. He does not have the knowledge to do that successfully for people. i.e. Jaminet for some of his errors was more level-headed about this part of biology and GH fits into his ideas. Not trying to be a **** for no reason, I have been falling into this line of thinking about GH for some time - food at nighttime always ends up poorly for me - so personally I will be looking for this hormone at some point in my life (since I have been so sick I don't expect to outlive Peat or anything so maybe the scope of some of his ideas just doesn't apply to me). Anyway I didn't finish reading it (one helluva night) but I've been waiting for studies on GH + DHEA combined so this made me giddy like a schoolgirl. Metformin is kind of interesting because I wouldn't have thought to throw that in, so I dunno about that one, though one or two enzymes come to mind The Antidiabetic Drug Metformin Activates the AMP-Activated Protein Kinase Cascade via an Adenine Nucleotide-Independent Mechanism...

(I'm willing to bet my life on it, so whenever I get there I'll let you know how it goes :3)

 

[haidut]

You could be right about enhanced conversion into estrogen/estrone depending on circumstances, haidut, but GH is a nighttime healing hormone. It replaces cortisol and permits the liver methylation cycle. It works together with thyroid and DHEA. In my opinion he is wrong about that hormone insofar as we evolved an importance for it in the circadian rhythm. He sees nighttime as a stressor to be counteracted in every way and in his mind nighttime food restriction should be abolished for our ultimate benefit - which someday might be the optimal solution - but that is unrealistic for our current knowledge - he is really thinking what we could do with the knowledge we'd have 25-100 years from now or something. He does not have the knowledge to do that successfully for people. i.e. Jaminet for some of his errors was more level-headed about this part of biology and GH fits into his ideas. Not trying to be a **** for no reason, I have been falling into this line of thinking about GH for some time - food at nighttime always ends up poorly for me - so personally I will be looking for this hormone at some point in my life (since I have been so sick I don't expect to outlive Peat or anything so maybe the scope of some of his ideas just doesn't apply to me). Anyway I didn't finish reading it (one helluva night) but I've been waiting for studies on GH + DHEA combined so this made me giddy like a schoolgirl. Metformin is kind of interesting because I wouldn't have thought to throw that in, so I dunno about that one, though one or two enzymes come to mind The Antidiabetic Drug Metformin Activates the AMP-Activated Protein Kinase Cascade via an Adenine Nucleotide-Independent Mechanism...

(I'm willing to bet my life on it, so whenever I get there I'll let you know how it goes )

Did you read the actual anti-aging study? Its authors themselves caution about growth hormone causing diabetes and that's why they added DHEA - i.e to negate those pro-diabetic effects of HG. In fact, they themselves say that in the doses they used in the study HGH can have harmful effects on the thymus! Again, what a bizarre study design, yet so common in mainstream medicine. Let's give you a drug that can give you cancer and diabetes and may even be unproductive for the very purpose we need it for. But not to worry, we will give you 2 other drugs that can (maybe) block these side effects. /s
From the study itself:
"...Because GH‐induced hyperinsulinemia (Marcus et al., 1990) is undesirable and might affect thymic regeneration and immunological reconstitution, we combined rhGH with both dehydroepiandrosterone (DHEA) and metformin in an attempt to limit the “diabetogenic” effect of GH (Fahy, 2003, 2010; Weiss, Villareal, Fontana, Han, & Holloszy, 2011).

I am not going to get into a debate about GH except to say that it is a known carcinogen when used in doses needed for ergogenic or anti-aging effects. Not at all surprising considering HGH increases fatty acid oxidation, which btw is the mechanism through which it causes diabetes as well.
https://www.webmd.com/colorectal-cancer/news/20020725/growth-hormone-linked-to-cancer
https://medicalxpress.com/news/2017-10-growth-hormone-cancer.html

Oh, last but not least - metformin. A known inducer of lactic acidemia and carcinogenesis. It really is hard to imagine a more dangerous approach to anti-aging.
Baking Soda May Treat Cancer, Metformin May Cause It

 

[LeeLemonoil]

@Terma.
Metformin is the staple-drug in anti-age and longevity circles and research, along with Rapamycin.
Reducing mTor-pathway and activating AMPK is what most of the thinking circles around yes.

In this Forum we have compiled data and publications against Metformin, especially because it is mitotoxic - life-extenders though consider it mito-hormetic and thus health-enhancing by mitophagy of defective mitos. I prefer to err on the side of caution and abstain from Metformin, my insulin sensitivity is in order and Mito health can be influenced by other more risk-free means.

As can GH. Taking Gaba plain and simple before sleep for example.
GABA - An Effective Sleep Aid W/ GH Boosting Effects that Works Within 30 Minutes - Only 100 mg Pre-Bed Will Suffice - SuppVersity: Nutrition and Exercise Science for Everyone

If you are interested, there is much recent research and screening going on for Metformin and Rapamycin - mimetics.
Allantoin is a potent Metformin-mimetic and freely available.
Interestingly, Withaferin A was found to mimic both Rapa and Met. It’s a steroidal lactone and might be interesting from a peaty perspective. Don’t know if it’s possibly estrogenic though, i think not but not read up on it

@haidut
Those indications on GH being pro-cancerous are concerning, though I take it as always context matters. 100mg of GABA seem to triggers GH and also elastin synthesis, both seems pro-regenerative and probably also cancer protective when used sensibly

 

[Terma]

Yes, it increases fatty acids and causes a state of pseudo insulin resistance. At nighttime. For peripheral and skeletal healing. To spare glucose for the brain. Glucose is a poor substrate for nighttime skeletal healing. GH is doing exactly what it needs to do in that circumstance. That's the same time carnitine reaches its top importance.

This is not a focus on the thymus.

I already know about the problems with metformin, but simply knowing an AMPK inducer was for some reason involved in this is potentially important information for me.

Don't worry, I prefer to keep things nice and short too, that's why I'm not going full Travis on you (he would probably hate me even more right now for promoting methylation - whatever guys I'm just following the leads :) ).

 

[Terma]

@Terma.
As can GH. Taking Gaba plain and simple before sleep for example.
GABA - An Effective Sleep Aid W/ GH Boosting Effects that Works Within 30 Minutes - Only 100 mg Pre-Bed Will Suffice - SuppVersity: Nutrition and Exercise Science for Everyone

Yeah I still have to get that, thanks for that one. I forgot lol