hamtaro
#164
Excellent video. One of the most informative ever, and a very strong case for 17a-estradiol. Already taking a PDE5 inhibitor, and keeping my eye on the SGL2 inhibitors.
New paper:
The effects of 17α-estradiol treatment on endocrine system revealed by single-nucleus transcriptomic sequencing of hypothalamus
In this study, we investigated the role of 17α-estradiol in lifespan extension and its potential side effects for long-term administration. Pooled hypothalami from aged male Norway brown rats treated with 17α-estradiol (O.T), aged male controls (O), and young male controls (Y) were subjected to single-nucleus transcriptomic sequencing (snRNA-seq). To evaluate the effects of 17α-estradiol in anti-aging in neurons, supervised clustering on neurons by neuropeptides and their receptors were used to evaluate the responses of each neuron subtype during aging and after 17α-estradiol treatment. The elevated cellular metabolism, stresses and decreased synaptic activity in neurons initiated by aging were remarkably attenuated by 17α-estradiol. Assessment of changes in neuron populations showed that neurons related to food intake, reproduction, blood pressure, stress response and electrolyte balance were sensitive to 17α-estradiol treatment. 17α-estradiol treatment not only increased Oxytocin (Oxt), but also increased the activity of hypothalamic-pituitary-gonadal (HPG) axis, evidenced by significantly elevated levels of plasma Gnrh, bioavailable testosterone, and decreased estradiol. Elevated Gnrh1 was verified to be one of the causal effects mediating the role of 17α-estradiol in energy homeostasis, neural synapse, and stress response. Notably, Crh neurons displayed most prominently senescent phenotype among all checked neuron subtypes in O.T, which may be a potential side effect of 17α-estradiol treatment. Therefore, HPG axis and energy metabolism may be key targets of 17α-estradiol in male lifespan extension. Additionally, supervised clustering of neurons was shown to be a useful method to assess the responses to treatment among different neuron subtypes in the hypothalamus.
https://www.biorxiv.org/content/10.1101/2024.06.14.599053v1#:~:text=17α-estradiol%20treatment%20not%20only,bioavailable%20testosterone%2C%20and%20decreased%20estradiol.
PDF:
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Bicep
#166
I bought a small amount of pomegranate seed oil and started taking maybe 1cc per day. Maybe 4 days in a row. My skin has never been so smooth. I really didn’t expect anything to happen and have several questions since I have no knowledge on this subject at all.
How much do I absorb through the gut? I expected it to be digested and not survive the stomach. Since I’m taking estrogen with the 17 alpha, is that good too as long as the side effects aren’t annoying? My last checkup my estriol was 17 I think, which is low but not too low.
I welcome any input, thanks.
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I can find no studies that taking pomegranate seed oil raises estradiol in men.
In one study it reduced menopausal symptoms in women without raising serum estradiol levels. In another study it only mildly increased levels in women.
Several studies say that it increases collagen production and improves skin.
I don’t know for sure, but I don’t think it is going to significantly raise estradiol serum levels in men.
As for cognitive benefits: A study ([4]) investigated a nasal delivery system for pomegranate seed oil and found that nasal administration in a phospholipid oily gel formulation significantly improved memory and locomotor activity in animal models compared to oral administration, suggesting that nasal delivery may enhance the potential cognitive benefits of pomegranate seed oil."
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Characterization of craniofacial tissue aging in genetically diverse HET3 male mice with longevity treatment of 17-alpha estradiol
Conclusions:
The HET3 mice present an excellent model with which to study the heterogeneous nature of tooth aging and the effects of longevity interventions. We provide novel data on how 17αE2 improves healthspan by modifying age-related changes in the molar dentin and cementum of male mice.
Open Access Paper:
https://www.sciencedirect.com/science/article/pii/S0003996924002917
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I have an estradiol Rx for “gender dysphoria” (as 17-alpha-estradiol is hard to get), should I be worried about 17beta-E2’s DNA binding activity?
jnorm
#170
Sadly we don’t know the doses Longevica used in their patent. I doubt it’s a concern with Rx doses though, and the UK Biobank associations support this.
Out of the 406 drugs studied, 169 had a significant effect on lifespan, after multiple comparison correction (FDR < 0.05). From these 169, as expected, the majority (N = 155, 92%) were associated with increased mortality (Figure 1, Data Table 2 ). These included notably opioids like Morphine sulfate (HR 5.56, CI 4.51-6.86) and Oramorph (HR 5.38, CI 4.08-7.09), the diuretic Furosemide (HR 2.00, CI 1.86-2.15), pain medication Paracetamol (HR 1.48, CI 1.42-1.55) or chronic obstructive pulmonary disease treatment Tiotropium (HR 1.96, CI 1.77-2.17). Importantly, we identified 14 drugs that increased lifespan, compared to health matched controls, independently of current smoking, cancer diagnosis, diabetes, gender, and age at recruitment. These included notably the statin Atorvastatin (HR 0.91, CI 0.87-0.95), the PDE5 inhibitor Sildenafil (HR 0.85, CI 0.78-0.93), the anti-inflammatory drug Naproxen (HR 0.90, CI 0.85-0.96), and the estrogen related drugs Estraderm (HR 0.67, CI 0.51-0.88), Vagifem (HR 0.73, CI 0.59-0.91), Estriol (HR 0.74, CI 0.60-0.92) and Estradiol (HR 0.75, CI 0.59-0.95). Others included, Lymecycline, Otomize, Marvelon, and 2 vaccines (Avaxim, Revaxis).
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A new PHD dissertation on this topic:
Evaluating Mechanisms by Which 17α-Estradiol Elicits Health Benefits Across Species
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Protection against APOE4-associated phenotypes with the longevity-promoting intervention 17α-estradiol in middle-aged male mice
Conclusions
These findings demonstrate that APOE4 promotes systemic and neural aging phenotypes linked to AD and that 17αE2-mediated healthspan actions show a positive APOE4 bias. Collectively, the findings suggest that longevity-promoting interventions may be useful in mitigating deleterious age-related risks associated with the APOE4 genotype.
Open Access Paper:
https://www.nature.com/articles/s43856-025-00942-3
3 Likes
jnorm
#173
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Keto Diet creates oxidative stress promoting senescence cells in mice. Thanks to estradiol, female mice don’t suffer from this problem:
Divergent sex-specific effects on a ketogenic diet: Male, but not female, mice exhibit oxidative stress and cellular senescence
https://www.cell.com/cell-reports/fulltext/S2211-1247(25)00797-1
This is crucial when analyzing ketogenic studies, we need to check the gender of the mice used!
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hamtaro
#175
I’m curious. Has anyone tried making a topical 17-Alpha Estradiol cream for use on skin/face? Maybe in this case, sourcing from China would be ok??
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Bicep
#176
Pomegranate seed oil is intended for use on hair and skin. It contains trace amounts really nobody can tell you how much since it’s a natural product. Sure makes skin smooth.
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I agree - this is something that we should look into. I’m less concerned about small impurities for topical agents. What do other people here think?
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No thanks. It is designed to be absorbed dermally. If it is absorbed, I’d like to be reasonably sure that I know just what it is that I’m absorbing. And therefore my standard MO to China origin products applies: avoid as much as is feasible any food items, or anything going into your body. One day it may change, when the regulatory environment over there changes, but as of now we’re not there yet. Of course we simply can’t avoid some things where ingredients in meds or supps come from nowhere else and there are no alternatives, but you do what you can. YMMV.
hamtaro
#179
I would be willing to also to pay for a chemical analysis. To measure Beta percentage, and impurities/contaminants. Don’t know how much that would be though.
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I am less concerned about purity of topical as well.
The 17-alpha estradiol is likely to be absorbed transdermally, but I would suspect that most contaminants would not be. However, there is the issue brought up in some of the initial posts in this thread, that 17-Alpha estradiol is going to be, in most cases, manufactured with 17- beta estradiol and the trick in getting the 17 alpha version is the separation of these two chiral molecules. So there could very well be significant amounts of the beta version (i.e. regular “Estradiol”) that is very feminizing. So there is that risk to be aware of and test for if someone goes down this route.
5 Likes
59vw
#182
Yeah I think I’d want to test it regardless of the route of administration.
1 Like
How do we go about organizing this? Can we find a source people would be willing to put money towards ordering a sample from and testing, and then if it is good we do a group buy?
