17-Alpha Estradiol - Another Top Anti-Aging Drug

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#58

Did we miss this paper? (and yes, more good news on 17-alpha estradiol)…

Health benefits attributed to 17α-estradiol, a lifespan-extending compound, are mediated through estrogen receptor α

17α-estradiol treatment improves metabolic parameters and slows aging in male mice. The mechanisms by which 17α-estradiol elicits these benefits remain unresolved. Herein, we show that 17α-estradiol elicits similar genomic binding and transcriptional activation through estrogen receptor α (ERα) to that of 17β-estradiol. In addition, we show that the ablation of ERα completely attenuates the beneficial metabolic effects of 17α-E2 in male mice. Our findings suggest that 17α-E2 may act through the liver and hypothalamus to improve metabolic parameters in male mice. Lastly, we also determined that 17α-E2 improves metabolic parameters in male rats, thereby proving that the beneficial effects of 17α-E2 are not limited to mice. Collectively, these studies suggest ERα may be a drug target for mitigating chronic diseases in male mammals.

Full Paper:

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#59

Any idea where we can get it? I have yet to see a vendor offer it.

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#60

The only two sources I know - reputable lab/chemical supply companies (need to know someone who runs a chemistry/biology lab, or related company) but I’d be sure to avoid any Chinese suppliers (see messages from one user’s experience earlier in this thread), or:

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#61

One other idea - contact this company and try to get into the clinical trials:

17a Estradiol´s Application in Humans

We at Apollo Health Ventures are very optimistic, given that 17-α estradiol is one of only a handful of drugs that caused life extension in ITP trials. Due to the promising results in animals Apollo Health Ventures (Apollo.vc) has started the company Apollo Alpha Inc. and is currently working on developing 17-α estradiol as a human drug.

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#62

@RapAdmin

Re Apollo, drilled down into their stable of companies.

Did you see this one:

“Aeovian Pharmaceuticals is a San Francisco Bay Area-based R&D-stage biopharmaceutical company developing novel and highly selective therapeutics modulating the mTORC1 pathway.

Addressing the mTORC1 pathway has been challenging to-date however, because chronic treatment with conventional, non-selective mTOR inhibitors, such as rapamycin and Everolimus, leads to off-target inhibition of mTORC2 which results in dose-limiting deleterious effects on metabolic health and immune function. The associated toxicity leads to severe clinical adverse events that significantly reduce treatment safety, decrease compliance, and compromise therapeutic efficacy.

In contrast, by virtue of their selectivity, our compounds potently inhibit mTORC1, but avoid inhibition of mTORC2, and therefore are not expected to cause the mTORC2-related side effects that limit the conventional non-selective mTOR inhibitors. We believe that the exquisite selectivity of our compounds for mTORC1 will enable a significantly improved safety profile resulting in improved tolerability, patient compliance, and ultimately improved efficacy in treating mTORC1-mediated rare and age-related diseases.

Our proprietary platform is supported by an extensive intellectual property portfolio, part of which has been obtained by assignment from the Buck Institute of Novato, California, the nation’s first independent research facility focused solely on understanding the connection between aging and chronic disease.”

Lamming is a scientific advisor.

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#63

Yes - its listed in my summary of all the different types of rapamycin and rapalogs on the market: Rapamycin Naming Conventions (part 2)

I think this is a bit of an issue for Dudley Lamming as publicly he’s quite “cool” on rapamycin (generally speaking) and I suspect it could be because he stands to make a lot of money off Aeovian stock if they are successful with their mTOR inhibitor (a direct competitor to rapamycin).

Ultimately - the more effective drugs for aging, the better for all of us, though I wonder what the cost will be of these new mTOR inhibitors if they come to market. Everolimus was about $6K per month prior to going off patent (if you didn’t have coverage by insurance)… Will the Aeovian mTOR inhibitor be $6K a month better than rapamycin… we’ll see.

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#64

Lamming is highly conflicted, but I’m ok with that, as long as his science is above reproach and truly moves the longevity needle. I fear you are right re eventual cost for a new mTOR inhibitor. These folks are not running a charity.

#65

This quite the interesting molecule, apparently not working predominantly via mTOR (although it does signal), but major liver gene expression.

“In alignment with our previous reports, 17a-E2 reduced calorie intake, body mass, adiposity, and obesity-related metabolic perturbations in male WT mice. These studies, coupled with our current findings, led us to speculate that 17a-E2 may be signaling through ERa in the liver to reverse metabolic disease and potentially extend healthspan and/or lifespan in males. We found that 17a-E2 dramatically reduced liver mass and lipid content”

I found the male/female selective responses quite profoundly interesting, especially as it relates to some further confirmations of the loss of most likely protective estrogen in post menopausal women and elevated aging chronic disease risk.

“The loss of endogenous estrogen action due to menopause in humans or ovariectomy (OVX) in rodents eliminates these beneficial effects and elicits metabolic perturbations. Moreover, OVX following sexual maturation has also been shown to reduce lifespan in female mice, indicating that endogenous estrogens regulate lifespan in females; which we surmise is at least partially mediated through ERalpha” This is pretty profound stuff if translatable to human female aging.

There’s a huge stack of smoking gun literature, especially for neurodegeneration in females associated with loss of estrogen late life.

And fundamentally, castrating male mice (blocking testosterone) completely ABLATED the effects of this molecule…wow.

“Despite these contrasting observations, the studies by Garratt et al. do provide important insights into the interconnected and under appreciated relationship between androgen- and estrogen-signaling pathways and their roles in metabolism and aging.”

“Notably, it is plausible that 17a-E2 could be inducing metabolic benefits and lifespan-extending effects through several distinct mechanisms, including direct actions through ERa, suppression of DHT production, and/or aromatization of testosterone”

https://www.sciencedirect.com/topics/medicine-and-dentistry/17alpha-estradiol

“17-α Estradiol is a weak estrogen and a potent 5-α reductase inhibitor” Another fascinating connection.

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#66

Quick question - why 60 mg instead of the original 2mg/day as planned?

#67

Is Discussed again by Dr. Stanfield (towards the end):

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#68

I am really interested in trying this drug, and would be willing to do any type of group buy with anyone else here. That could potentially involve doing a very thorough 3rd party analysis if necessary.

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#69

Im an LP with Apollo. I’ll ask them if thats a possibility, as I’m interested also.

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#70

They could probably recruit a bunch of people for their clinical trial quite quickly here :smile:

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#71

Anyone interested in taking 17-alpha estradiol may want to review this 1999 Summary write-up on Estrogens in the male, variations by age, etc… It seems to cover normal levels of these types of hormones in males, and implications of higher and lower levels, etc. See below:

Estrogens in the Male.pdf (2.9 MB)

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#72

An interesting new 2022 Doctoral Thesis by Jose Victor Vieira Isola on the topic of 17 alpha estradiol and aging (incorporating a number of studies in mice).

It has some good information on the impact of 17 alpha estradiol’s effects on reproductive aging (with both Portuguese and English in the body of the paper. (scroll down to get to the english parts that are scattered throughout the document).

17 alpha-Estradiol and caloric restriction in male and female reproductive aging

Jose-Victor-Vieira-Isola.pdf (2.1 MB)

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#74

I asked. They are only testing animals atm.

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#75

“17a-Estradiol signicantly increased in the Shenling Baizhu Powder treatment group and was positively correlated with Lachnospiraceae and Allobaculum_ stercoricanis.”

Effects of Shenling Baizhu Powder on PyrotinibInduced Diarrhea: Analysis of Gut Microbiota,Metabonomics, and Network Pharmacology

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#76

Anyone know how to get this supplement?

#77

You’re talking about this supplement that @Toxidendron just mentioned: Shenling Baizhu Powder?

Just google it/shopping and there are many options, but from my perspective some random selection of chinese herbs is interesting, but not something I’d want to take on an ongoing basis, given the pollution / quality problems of chinese supplements and drugs. And, while its interesting that 17-alpha estradiol increased in the SBP group, who knows what else the herbal mixture is doing, and how it interacts with other supplements or drugs we are taking?

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#78

I would rather get a western version of 17 alpha estradiol. Is there anything available yet?