IL-17 Protein Plays an Important Role in Skin Aging, FDA Approved Therapies Available

They measured in blood. What I think we really want to know is how much IL-17 inhibition happens in the skin… wouldn’t we want a skin biopsy / tissue sample measure to better understand that. I don’t have much experience in this area - how representative is the blood measure, for skin measures?

Methods: Blood samples were drawn from 10 active VKH patients and 10 healthy individuals. PBMCs were cultured with or without anti-CD3 and anti-CD28 antibodies in the presence or absence of different concentrations of RAPA or DEX for 72 h

Full Research Paper here:

Inhibitory effect of rapamycin and dexamethasone on production of IL-17 and IFN-γ in Vogt–Koyanagi–Harada patients

https://sci-hub.ee/10.1136/bjo.2008.142489#

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This might help make an argument for higher dosing pulsed over longer periods of time… similar to the blood brain barrier issue / argument: Rapamycin and the Issue of Getting Through the Blood Brain Barrier

But it also suggests that with whatever dosing levels of rapamycin that people are using, they are likely getting some skin anti-aging benefits along with other organ, etc. anti-aging benefits.

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There are some companies offering blood tests for systemic IL-17 levels…

What I really wanted to find was a skin-level test that was commercially available. I found this paper on a skin biopsy method of evaluating IL-17 levels and it seemed to work when evaluating skin with psoriasis lesions, but not in regular skin … so it doesn’t sound like the IL-17 skin testing technology is quite where I’d like to see it.

Full Paper Available for Download (PDF): https://sci-hub.ee/10.1208/s12248-017-0094-4

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I’ve been researching RAPA as a potential substitute for Methotrexate, which I take for psoriatic arthritis. MTX doesn’t work that well and has frustrating side-effects, thinning skin being one of them. Thank you for this information.

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Th17 cells have recently emerged as a major player in inflammatory and autoimmune diseases via the production of pro-inflammatory cytokines IL-17, IL-17F, and IL-22. The differentiation of Th17 cells and the associated cytokine production is directly controlled by RORγt. Here we show that ursolic acid (UA), a small molecule present in herbal medicine, selectively and effectively inhibits the function of RORγt, resulting in greatly decreased IL-17 expression in both developing and differentiated Th17 cells. In addition, treatment with UA ameliorated experimental autoimmune encephalomyelitis. The results thus suggest UA as a valuable drug candidate or leading compound for developing treatments of Th17-mediated inflammatory diseases and cancer.

Ursolic Acid Suppresses Interleukin-17 (IL-17) Production by Selectively Antagonizing the Function of RORγt Protein*

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Yep, I think I will just stick to rapa to inhibit IL-17.
From the article you cite:

Both RAPA and DEX were able to significantly inhibit the production of IL-17 and IFN-γ by PBMCs from patients and healthy controls. RAPA was able to completely inhibit IL-17 production at a dosage of 10 ng/ml but only partially suppressed IFN-γ production even at a much higher concentration (1000 ng/ml). DEX inhibited the production of both IL-17 and IFN-γ by approximately 70%.

Conclusions: This study indicates that both RAPA and DEX inhibit the production of IL-17 and IFN-γ by PBMCs. RAPA is much stronger in inhibiting the production of IL-17 than DEX.

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That IL-17 inhibition might explain why rapamycin may help with hair growth and graying:

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Just realized that yes, we’ve discussed this compound in the past in the hair graying thread: Reverse Gray Hair, Hair Repigmentation - #38 by HawksFan

Seems like multiple lines of evidence are converging a bit here…

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Interesting comments by “Reason” of Fight Aging, seems to confirm the idea that trying to target just the skin may be a winning approach with this IL-17 protein and the existing drugs that can be used to inhibit it. At some point in the not too distant future I think I’d like to try the mesotherapy approach that @LaraPo has described in the past, using the existing IL-17 inhibitor drugs that were mentioned earlier in this thread. Perhaps this might also work with micro-needling approaches on the scalp for hair regrowth and repigmentation.

I also wonder if there is potential to use a mesotherapy version of a rapamycin injection formulation given the good inhibition of IL-17 that rapamycin has shown in studies. Sort of a “rapamycin injection Lite” version of what @Mac has done with his protocol: Intramuscular (IM) + Intranasal (IN) Rapamycin - A new paradigm for human longevity translation

The researchers show that blocking IL-17 slows the manifestations of skin aging. The challenge in this sort of approach is that inflammatory signal molecules are needed for the normal immune response to function correctly. The treatment of autoimmune conditions via blockade of various inflammatory signals has meaningful side-effects that include suppression of necessary immune responses. This is less of a concern if treatments target only the skin, but we should hope that researchers can identify more targeted, subtle ways to eliminate only excess inflammatory signaling in the rest of the aging body.

Source: https://www.fightaging.org/archives/2023/06/targeting-pro-inflammatory-cytokine-il-17-to-slow-skin-aging/

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What is considered a “typical dose” of Rapa for aging? I take 5mg per week and am curious if that’s considered typical.

Yes - that is about average, or the median. See our poll here: What is the Rapamycin Dose / Dosage for Anti-Aging or Longevity?

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@desertshores What dose of Rapa are you currently taking?

Thank you for referring me back to that thread, completely forgot about it.

5 mg per week is definitely a typical dose. For more detail see the poll RapAdmin linked to.

5mg once weekly with EVOO.

Are you still taking it with GFJ?

Lara what intradermal injections are you doing if I could ask?

I do all kinds of mesotherapy injections for my face and hands. I use Citocare 532, Mesohyal, Korean Ultra White and Ultrahilo. I also used Juvederm products (skin fillers).

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Here’s another

IL-17 mediates immune responses against extracellular pathogens, and it is associated with the development and pathogenesis of various autoimmune diseases. The expression of IL-17 is regulated by various intracellular signaling cascades. Recently, it has been shown that mechanistic target of rapamycin (mTOR) signaling, comprised mainly of mTORC1 signaling, plays a critical role in IL-17 expression. Here, we review the current knowledge regarding mechanisms by which mTORC1 regulates IL-17 expression. mTORC1 positively modulates IL-17 expression through several pathways, i.e. STAT3, -HIF-1α, -S6K1, and -S6K2. Amino acids (AAs) also regulate IL-17 expression by being the energy source for Th17 cells, and by activating mTORC1 signaling. Altogether, the AA-mTORC1-IL-17 axis has broad therapeutic implications for IL-17-associated diseases, such as EAE, allergies, and colitis.

Full Paper (open access):

https://onlinelibrary.wiley.com/doi/10.1002/eji.201545886

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