Inhibiting type 1 systemically is probably tilting towards being a net negative but I don’t know of any potent topical 5ar type 1 inhibitor that doesn’t go systemic. Topical dutasteride probably doesn’t even work at all.
How many people actually use oral alfatradiol?
It’s like claiming research substance XYZ doesn’t have any reddit anecdotes of negative side effects therefore it is more efficious and safe than known medication ABC that’s been around for 70 years and been researched thousends of times.
Either inhibiting 5ar, regardless of method, leads to PFS (despite no actual biological mechanism existing and case reports hinting at mental illness) in which case oral alfatradiol would lead to the same side effects or finasteride and dutasteride have properties that alfatradiol doesn’t have which is doubtful.
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17 alpha estradiol shows good lifespan effects in ITP, this is why I’m interested in it.
It is probably good for the skin applied topically.
You’re right though, not enough people using it to find negative effects compared to something like finasteride or dutasteride.
I’d say 17 alpha estradiol would have different properties to fin/dut. It’s not just 5AR inhibition.
I hear topical estriol cream is good for the skin as well. I wonder if men can use that without feminizing effects.
Yes, but my point is that barely any human on this planet is actually using it.
It is probably good for the skin applied topically.
At higher doses than currently available.
I’d say 17 alpha estradiol would have different properties to fin/dut. It’s not just 5AR inhibition.
But if used at high enough doses orally (or even topically), you get systemic DHT inhibition just like with finasteride and dutasteride. If side effects are related to that, using alfatradiol won’t help. And unlike finasteride I believe alfatradiol inhibits both 5ar type 1 and type 2.
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Any thoughts on topical estriol cream?
Estriol absorbs readily through the skin so you’ll absolutely experience some feminization from it.
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This thread seems to be a bit all over the place but if anyone is still looking for elastin neogenesis in the SKIN the answer is calcium hydroxyapatite — the same ingredient in remineralizing fluoride free toothpaste. It’s a key ingredient in bones and teeth but can also serve as scaffolding for new skin tissue and for revitalization, and has explicitly been shown to generate new elastin. The brand name is Radiesse and the way to optimize elastin generation is using it in hyperdilute form (i.e. cut with saline in a ratio of 1:2) via mesotherapy OR, in my case, dermoelectroporation. I couldn’t be happier with my results so far but at $45 / syringe from my Chinese supplier, I find it a bit pricey for just 3 cc. If there’s no better deal for it it’s still amazing but I will experiment with just buying the powder and mixing it with water myself. Will try to see if that also yields results on belly / arm skin (anywhere but face and neck to try). Still $45 every 4 weeks for 3-4 treatments a year is a piece of cake for most. And I can speak from experience that it’s awesome.
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According to this study no systemic hormonal side effects were noted with topical estriol used for reduction of skin aging:
“After treatment for 6 months, elasticity and firmness of the skin had markedly improved and the wrinkle depth and pore sizes had decreased by 61 to 100% in both groups. Furthermore, skin moisture had increased and the measurement of wrinkles using skin profilometry, revealed significant, or even highly significant, decreases of wrinkle depth in the estradiol and the estriol groups, respectively. On immunohistochemistry, significant increases of Type III collagen labeling were combined with increased numbers of collagen fibers at the end of the treatment period. As to hormone levels, only those of PRL had increased significantly and no systemic hormonal side effects were noted.” TREATMENT OF SKIN AGING WITH TOPICAL ESTROGENS
Full study without paywall:
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The full text link doesn’t work for me, but I can see the date of the paper and it says 1996?
You need to let it load for a while. That website has these studies hosted on a very slow server.
But I will upload it here for now:
TREATMENT OF SKIN AGING WITH TOPICAL ESTROGENS – JOLANTA B_ SCHMIDT; MARTINA BINDER; GABRIELE DEMSCHIK; – International Journal of Dermatology, #9, – 10_1111_j_1365-4362_1996_tb03701_x – 4458c31f904775bcf58e79.pdf (5.2 MB)
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I have extreme ongoing elastin production at age 64, it seems. Passed every relevant test I found via Grok-AI for it. Any questions you might have for me?
Yea what is your diet, lifestyle, exercise, supplement, drug protocol
I’m still interested in diet, lifestyle, exercise, supplement and drug protocol if you get this message. Also curious if you have any particular health issues/diseases/illnesses that might be unknowingly causing some kind of elastin generating effect.
Still interested if you see this message.
Thanks for the detailed summary! 
It’s really helpful to see all the current and emerging strategies for neoelastinogenesis in one place. From what you’ve outlined, it’s clear that combining daily protective measures like sunscreen and topical retinoids with clinical interventions such as microneedling, RF, or high-frequency ultrasound can maximize elastin preservation and regeneration.
I also appreciate the inclusion of emerging biotech approaches like ELR peptides, RiboScreen™, and cell-based therapies — exciting to see how regenerative medicine is moving beyond just cosmetic improvements to supporting tissue health and longevity.
For anyone looking to maintain healthy elastin as part of anti-aging routines, this thread is a great roadmap for evidence-backed strategies.
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Since elastin is critical for a healthy old age and there is currently no way to restore elastin in a systemic way, what we are currently left with is still a good thing. Fixing or improving CVD, Cancer, Stroke, COPD, etc. outcomes are quite possible in the next couple of decades.
While fixing the top 4 causes of death in the aged is not going to increase maximal life span, I’m still hoping to be on that train 
Fixing the elastin problem is significantly harder than any of those.
Which is why there is so little research in this area. Even the great AdG is not working on this. Why not? it is the hardest thing to fix compared to the 4 major killers related to aging.
No fix for the elastin problem on the horizon.pdf (290.2 KB)
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I think this is a splicing thing.
Damage accumulation in long-living macromolecules (especially extracellular matrix (ECM) proteins, nuclear pore complex (NPC) proteins, and histones) is a missing hallmark of aging. Stochastic non-enzymatic modifications of ECM trigger cellular senescence as well as many other hallmarks of aging affect organ barriers integrity and drive tissue fibrosis. The importance of it for aging makes it a key target for interventions. The most promising of them can be AGE inhibitors (chelators, O-acetyl group or transglycating activity compounds, amadorins and amadoriases), glucosepane breakers, stimulators of elastogenesis, and RAGE antagonists.
https://advanced.onlinelibrary.wiley.com/doi/10.1002/adhm.202400484
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I’ve gone through the very latest studies on elastin, picked the most relevant for what we are interested in and summarized why each of these studies are important. Here is what I’ve found:
Why this seems important: Afzelin is a potential collagen type 1 and elastin restoring compound.
“Results: Afzelin restored UVA-impaired cell viability and reduced β-galactosidase, p53, and p21 while recovering Lamin B1. It lowered ROS levels and restored mitochondrial membrane potential (2.8-fold) via AMPK-AKT/mTOR-ULK1 and PINK1-Parkin activation. Combined with GAA (50 mM), afzelin showed strong synergy (Bliss = 67.6 ± 5.1). In vivo, co-treatment reduced epidermal thickness ( ∼37.3 %), restored collagen I and elastin, and suppressed p53/p21 expression.
Conclusion: Afzelin alleviates UVA-induced photodamage by activating autophagy and mitophagy. Together with the anti-aging triterpenoid GAA, it exerts synergistic anti-photoaging effects, supporting its potential as a natural autophagy-targeting agent for skin rejuvenation.”
Afzelin resists UVA damage through autophagy and synergizes with ganoderic acid A to skin photoaging Afzelin resists UVA damage through autophagy and synergizes with ganoderic acid A to skin photoaging - PubMed
Why this seems important: Potentially important genes for rejuvenating elastin which could be explored in genetic reprogramming or other methods of targeting.
“The analysis revealed five protein-coding genes significantly associated with collagen III (P value < 2.44E-6, R2 > 0.5). Two protein-coding genes, including collagen III, were positively correlated with fibronectin, and five protein-coding genes were positively correlated with elastin.”
Transcriptome-wide analysis of genes associated with collagen III in human skin Transcriptome-wide analysis of genes associated with collagen III in human skin - PubMed
Why this seems important: By analysing mechanisms of elastin downregulation in diseased states we might uncover insights in how to recover elastin production or halt degredation/downregulation in all humans.
“In the diagnosed group, proteins such as MMP7, POSTN, and CD163 exhibited characteristic high-level expression. Furthermore, compared with the suspected group, the diagnosed group showed significant downregulation of proteins related to elastin fibers, indicating a more severe degree of fibrosis in the lacrimal gland tissues.”
Autoimmune fibroinflammation in IgG4-related ophthalmic disease: TLR8-dependent signaling pathways and fibrotic remodeling revealed by proteomic profiling Autoimmune fibroinflammation in IgG4-related ophthalmic disease: TLR8-dependent signaling pathways and fibrotic remodeling revealed by proteomic profiling - PubMed
Why this seems important: Synthetic elastic protein combined with ascorbic acid appears to improve elastic fibre formation.
“…imbalances in the components of the extracellular matrix (ECM) during tissue engineering often result in the deterioration of the mechanical properties and physiological relevance of dermal substitutes, in part due to the detrimental effect of ascorbic acid (AA) on elastic fibre biosynthesis. The objective of this study is to investigate the potential of a synthetic elastic protein (SEP) to improve ECM remodelling and to restore the equilibrium between collagen and elastin in reconstructed dermal tissues. Primary fibroblasts monolayers were treated with increasing concentrations of SEP in the presence or not of AA without affecting cytotoxicity. Western blot and immunofluorescence analyses showed that in the presence of AA - which typically reduced elastin synthesis- SEP improved elastic fibre formation without affecting type I collagen assembly.”
A Recombinant Elastic Peptide Rescues Elasticity From a Self-Assembled Dermal Sheet Model Treated With Ascorbic Acid A Recombinant Elastic Peptide Rescues Elasticity From a Self-Assembled Dermal Sheet Model Treated With Ascorbic Acid - PubMed
Why this seems important: Diabetes downregulates extracellular matrix remodeling genes and impairs elastin deposition after injury, suggesting that chronic inflammatory and metabolic signaling suppresses elastogenesis.
“…T1D and T2D mice displayed upregulation of genes associated with canonical chemokine/monocyte-mediated inflammatory pathways, and downregulation of genes associated with extracellular matrix remodeling… T1D and T2D delayed activation of M2-like (CD206+) macrophages in the heart, and impaired normal collagen and elastin deposition after MI.”
Distinct immunometabolic signatures of type 1 versus type 2 diabetes in a murine model of myocardial infarction Distinct immunometabolic signatures of type 1 versus type 2 diabetes in a murine model of myocardial infarction - PubMed
Why this seems important: Estrogen, and the agonism of various receptors appears to cause, among other seemingly good things, elastin synthesis.
“This review examines the mechanisms through which estrogen, acting via nuclear receptors (ERα and ERβ) and the membrane receptor G protein-coupled estrogen receptor (GPER), regulates pelvic floor connective tissue homeostasis through both genomic and non-genomic pathways. Key regulatory effects include the promotion of collagen and elastin synthesis, inhibition of matrix metalloproteinase (MMP) activity, modulation of fibroblast function-including mitigation of cellular senescence and enhancement of migratory and anti-apoptotic capacities-as well as integration with mechanical signaling through the integrin-YAP/TAZ axis.”
Multidimensional regulation of estrogen signaling in pelvic floor connective tissue homeostasis and remodeling Multidimensional regulation of estrogen signaling in pelvic floor connective tissue homeostasis and remodeling - PubMed
Why this seems important: Supraperiosteal implantation of polycaprolactone (PCL) microspheres appears to significantly promote elastin fiber formation.
“H&E and Masson’s trichrome staining revealed significantly enhanced collagen ingrowth in PCL microspheres compared to HA. Immunofluorescence staining showed substantial infiltration of type I and type III collagen within the PCL microspheres, with a predominance of type I collagen. EVG staining indicated that PCL microspheres significantly promoted elastin fiber formation.”
A Rat Model Investigation of Enhanced Facial Rejuvenation via PCL Microsphere-Induced Superior Collagen Neogenesis in the Supraperiosteal Plane A Rat Model Investigation of Enhanced Facial Rejuvenation via PCL Microsphere-Induced Superior Collagen Neogenesis in the Supraperiosteal Plane - PubMed
Why this seems important: Activation of the STING inflammatory pathway drives elastin disruption in abdominal aortic aneurysm, and its inhibition preserves elastin structure, suggesting STING signalling may be a key regulator of elastin degradation in inflammatory vascular aging.
“The STING signaling pathway was significantly activated in AAA tissues… Sting mutation slowed AAA formation, as confirmed by reduced AAA incidence, maximal abdominal aortic diameter, elastin disruption, collagen deposition, and inhibited immune cell infiltration…”
Inhibition of STING pathway attenuates experimental abdominal aortic aneurysm progression Inhibition of STING pathway attenuates experimental abdominal aortic aneurysm progression - PubMed
Why this seems important: Eggshell membrane appears to have some sort of skin structure regenerative property, seemingly related to collagen and elastin formation. Potentially biased industry funded study but worth further investigation.
“This study demonstrates that a 300 mg intake of fresh membrane MKARE® positively affects mechanical skin parameters compared to the group that consumed 8,000 mg of hydrolyzed collagen or the placebo group. These improvements suggest that MKARE® consumption regenerates the skin structure, primarily due to positive changes in collagen and elastin formation, which are key contributors to the improvement of skin firmness, elasticity, and barrier protection.”
Comparative effects of MKARE® eggshell membrane and hydrolyzed collagen as nutricosmetics on skin biophysical properties: a randomized clinical trial Comparative effects of MKARE® eggshell membrane and hydrolyzed collagen as nutricosmetics on skin biophysical properties: a randomized clinical trial - PubMed
Why this seems important: Vitamin B6 decreased elastin degradation. While I don’t think many people have vitamin B6 deficiencies and I don’t think vitamin B6 megadosing will solve elastin degradation, we may be able to create novel B6 like compounds or figure out what B6 is doing in the body to figure out new targets for elastin protection and/or regeneration.
“B6 supplementation significantly attenuated AD, as evidenced by reduced AD incidence, improved survival, preservation of aortic architecture, and decreased elastin degradation. B6 also exerted antioxidant effects, alleviating oxidative stress, which was associated with inhibition of smooth muscle cell phenotypic switching and reduced ECM degradation.”
Vitamin B6 attenuates aortic dissection by inhibiting pathological remodeling of the aortic extracellular matrix Vitamin B6 attenuates aortic dissection by inhibiting pathological remodeling of the aortic extracellular matrix - PubMed
Why this seems important: We already know that retinoids can have a positive effect on elastin production, but they are often irritating. Hydroxypinacolone 9-cis retinoate is a novel retinoid that may be able to be applied more often without irritation offering a more robust elastin and collagen rejuvenating effect for more effective aesthetic antiaging effect in the skin.
“Photoaging, driven by chronic ultraviolet radiation (UVR), disrupts skin structure and function. Traditional retinoids enhance extracellular matrix (ECM) regeneration but cause irritation. Hydroxypinacolone 9-cis retinoate (9-cis HPR), a derivative of 9-cis retinoic acid, selectively activates RARα and RXRα, improving efficacy and tolerability. In a UVR-induced SKH-1 mouse photoaging model, 9-cis HPR reduced erythema, desquamation, and loss of elasticity while promoting collagen and elastin production. Single-cell RNA sequencing and spatial transcriptomics revealed restoration of fibroblast, basal cell, and melanocyte proportions, suppression of myofibroblast differentiation, and upregulation of ECM-related genes (e.g., Col1a2, Col3a1, Elastin). Additionally, 9-cis HPR inhibited melanogenesis by downregulating melanogenesis-related genes (Tyr, Dct, Tyrp1), melanosome biogenesis genes (Mlana, Pmel), and the melanocyte proliferation gene Kit, likely via ROS suppression. Cell-cell interaction analysis showed that 9-cis HPR promoted fibroblast-driven repair via NPY-NPY1R, PTN-SDC2, and POSTN-ITGA/BV signaling, while inhibiting KITL-KIT-mediated melanocyte proliferation. In a single-blind, split-face clinical trial involving 31 Chinese women, 0.03% 9-cis HPR applied daily for 4 weeks demonstrated comparable or superior improvements in wrinkles, elasticity, hydration, dermal density, and radiance versus 0.3% retinol, without observed irritation. These findings support 9-cis HPR as a safe and effective retinoid that mitigates photoaging through ECM restoration, inflammation modulation, and pigmentation control.”
Hydroxypinacolone 9-cis Retinoate Mitigates UV-Induced Photoaging by Modulating ECM, Fibroblasts, Inflammation, and Melanogenesis Hydroxypinacolone 9-cis Retinoate Mitigates UV-Induced Photoaging by Modulating ECM, Fibroblasts, Inflammation, and Melanogenesis - PubMed
Why this seems important: The use of hydroxytyrosol loaded soluble microneedles upregulated elastin expression alongside a range of beneficial effects to reduce photoaging. This seems like a truly amazing treatment!
“Western blot analysis further revealed that HT MNs upregulated the expression of collagen type I alpha 1 (COL1A1), elastin (ELN), hyaluronan synthase 2 (HAS2), and filaggrin (FLG), while downregulating matrix metalloproteinase 1. Overall, these findings suggest that HT MNs effectively mitigate UV-induced photoaging through antioxidant, anti-senescence, and extracellular matrix (ECM)-regulating mechanisms, underscoring their potential as a novel transdermal anti-photoaging therapy.”
Anti-Photoaging Effect of Soluble Microneedles Loaded with Hydroxytyrosol Anti-Photoaging Effect of Soluble Microneedles Loaded with Hydroxytyrosol - PubMed
Why this seems important: This dual hyaluronic acid compound was shown to increase elastin and collagen production alongside numerous other beneficial effects promoting skin rejuvenation.
“This study investigated the multimodal rejuvenation potential of a dual hyaluronic acid compound (DHC), composed of low- and high-molecular-weight HA integrated within a minimally cross-linked hybrid complex. In vitro assays using dermal fibroblasts, melanoma cells, and macrophages demonstrated that DHC enhanced fibroblast viability, collagen I/III and elastin production, antioxidant enzyme activity, and wound-healing capacity while reducing senescence markers.”
Regenerative Skin Remodeling by a Dual Hyaluronic Acid Hybrid Complex in Multimodal Preclinical Models Regenerative Skin Remodeling by a Dual Hyaluronic Acid Hybrid Complex in Multimodal Preclinical Models - PubMed
Why this seems important: Tirzepatide, a GLP1/GIP receptor agonist, appears to have powerful anti-inflammatory effects. Part of this appears to protect elastin integrity. I also hypothesize that tirzepatide and this class of drugs prevent some damage from glycation which would also protect elastin.
“This study offers initial experimental evidence that tirzepatide (TZP), a novel dual GIP and GLP-1 receptor agonist, significantly reduces formation and rupture, maintains medial elastin integrity, and inhibits VSMC phenotype switching and vascular inflammation in a BAPN-induced mouse model of TAAD. These protective effects are partially mediated by inhibiting NLRP3 inflammasome activation, as indicated by decreased expression of NLRP3, Caspase-1, and pro-inflammatory cytokines like IL-1β.”
Tirzepatide mitigates thoracic aortic aneurysm and dissection by alleviating the loss of the contractile phenotype in vascular smooth muscle cells and reducing vascular inflammation https://www.sciencedirect.com/science/article/abs/pii/S1537189126000017
Why this seems important: Silk fibroin restores elastin deposition by reversing fibroblast senescence and suppressing ROS–MAPK–AP-1–MMP signaling, identifying cellular aging and oxidative stress as upstream regulators of elastic fiber loss.
“Skin aging is characterized by a progressive decline in regenerative capacity, primarily driven by fibroblast senescence, oxidative stress, chronic inflammation, and the degradation of type I/III collagen, culminating in an extracellular matrix (ECM) imbalance. Current injectable fillers-such as hyaluronic acid, collagen, and PLLA-provide temporary structural support but fail to address the underlying cellular senescence or restore ECM homeostasis, highlighting the need for regenerative biomaterials. Silk fibroin (SF), a natural protein, self-assembles into a β-sheet-rich scaffold that structurally supports fibroblasts in depositing collagen and elastin, thereby improving the skin’s ECM, accelerating wound healing, and promoting tissue regeneration. However, its role in modulating fibroblast senescence and ECM remodeling remains unclear. This study demonstrates that SF provides a suitable microenvironment for the adhesion and proliferation of fibroblasts, reducing the accumulation of SASP factors and facilitating the transition of fibroblasts from a senescent to a functional state. Furthermore, SF improves the skin microenvironment by reducing reactive oxygen species (ROS) and matrix metalloproteinase (MMP) expression through modulation of the ROS-MAPK-AP-1-MMP signal pathway, thereby delaying collagen degradation in aged skin. These findings reveal that SF uniquely rejuvenates fibroblasts and restores ECM homeostasis through a non-inflammatory mechanism, distinguishing it from conventional fillers that rely on inflammatory pathways for collagen induction. This work establishes SF as a next-generation injectable biomaterial with dual targeting of cellular senescence and ECM imbalance, offering a transformative strategy for regenerative dermatology and personalized anti-aging approaches.”
Silk Fibroin Counteracts Fibroblast Senescence to Restore ECM Homeostasis in Aged Skin Silk Fibroin Counteracts Fibroblast Senescence to Restore ECM Homeostasis in Aged Skin - PubMed
Why this seems important: IL-16 appears to be incredibly important not just for preventing the degradation of elastin and collagen but for a wide variety of vital health functions for longevity.
“IL-16 deficiency increased the necrotic core and reduced fibrous cap thickness in the plaques. IL-16 deletion accelerated the degradation of intraplaque collagen and elastin, increased matrixmetalloproteinase activity, and reduced TIMP-3 expression. Transplantation of wild-type IL-16 bone marrow into IL-16 knockout mice successfully attenuated the plaque instability caused by IL16 deficiency.”
Interleukin-16 upregulates tissue inhibitor of metalloproteinase 3 to promote atherosclerotic plaque stability Interleukin-16 upregulates tissue inhibitor of metalloproteinase 3 to promote atherosclerotic plaque stability - PubMed
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