#85

unfortunately all the natural anti IL11 discussed always failed to show any lifespan extension.

The only things that is proven without off target is the antibody as described in the nature paper.

To be clear, they VVB Bio doesnt say much about their antibody, but others coming target the receptor, instead of the ligand. The effect shouldnt be the same.

So its veryyyyy unfortunate VVB Bio is so far from reaching the market, they will start phase 1 by 2026…

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#86

I think this technology could provide the answer. I don’t know much about the company, but it seems as if they are already working on lowering certain Cytokines. I imagine it could be fairly straightforward if their technology works and it seems to in animals so far.

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#87

Boehringer Ingelheim started a clinical trial in 2023 for first-in-class IL-11 inhibitor antibody BI765423.
Their focus with this il-11 inhibitor is to treat fibrosis.

https://www.boehringer-ingelheim.com/science-innovation/human-health-innovation/il-11-inhibitor-antibody-clinical-development-launched

https://clinicaltrials.gov/study/NCT05658107#study-overview

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#88

DoNotAge which is a supplement company posted on X they were announcing something relating to IL-11. I deactivated my X account so I don’t have it.

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#89

This paper seems to indicate that lutein does a fairly good job of inhibiting IL-11. Not sure how it compares to the AB.
Apologies for the scrappy reference…I hope the link works.

Redox Biology

Volume 44 August 2021, 102020

Lutein attenuates angiotensin II- induced cardiac remodeling by inhibiting AP-1/IL-11 signaling

Youming Chen a 1, Lan Wang b 1, Shixing Huang c 1, Jiangfeng Ke d, Qing Wang e, Zhiwen Zhou f, Wei Chang g

https://doi.org/10.1016/j.redox.2021.102020

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#90

Problem is, I seem to remember that IL-11 AB was given to humans in a dose of about 300 mg?
So one would expect that a bigger dose of lutein than that would be needed to have a similar effect. But lutein only comes in 10-20 mg tabs. 300 mg might well be toxic. More research is needed!

1 Like
#91

Yes, I’ve tried various GPTs/LLMs for this. But unfortunately, most of these suggestions seem to be hallucinations. If you google them one by one, you find that most of the evidence is related to IL-6 or inflammation broadly, except maybe omega-3.

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#92

Since humans are not limb-regenerating organisms like lizards, IL-11 seems to accelerate aging only by creating hyperfunction in organs. Then we have to get rid of IL-11. Additionally, IL-11 is the cause of unnecessary scar formation called hyperfibrosis. So all this supports the hyperfunctional theory of aging.

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#93

It’s weird because rapamycin stops limb regrowth in axolotls.

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#94

To investigate the antifibrotic effect of the blockage of the trans-signaling pathway of IL−11, we used TJ301 (sgp130FC), an inhibitor of IL−11 trans-signaling, as the intervention reagent. We observed that TJ301 could ameliorate skin and lung fibrosis in BLM-induced SSc mice by reducing skin thickness, collagen deposition, and COL3 expression. Cells treated with TJ301 could inhibit the expression of COL3 induced by iono in fibroblasts overexpressing IL−11. We further investigated whether the inhibition of the STAT3 pathway could reduce the profibrotic effect of IL−11 and observed that WP1066 (a JAK2/STAT3 inhibitor) could significantly reduce IL−11-induced COL3 expression (both classical and trans-signal transduction pathways) in fibroblasts.

Elevated ADAM10 level indicates the increased expression of sIL−11 Rα in the skin of SSc patients. We found that the binding of IL−11 to sIL−11 Rα induced fibrosis with elevated collagen expression, which suggests that the IL−11 trans-signaling pathway plays an important role in the pathogenesis of SSc. Researchers have reported that sgp130FC can block sIL−11 Rα. As sgp130FC can non-selectively block sIL−11 Rα or sIL−6 Rα and IL−6 plays a role in fibrosis in SSc, more research is needed to understand the trans-signaling role of IL−6 and IL−11 in fibrosis. In other words, sgp130FC may be a great potential anti-fibrosis therapeutic agent because it can block the trans-signaling pathway of IL−11 and IL−6 simultaneously without blocking IL−11 Rα or IL−6 R. The JAK/STAT pathway has been studied in SSc-associated ILD and IPF. We have demonstrated that blocking the JAK2/STAT3 pathway could inhibit the profibrotic effect of IL−11, suggesting that the small molecular JAK/STAT inhibitor is also an attractive target for fibrotic disease.

Investigational new drug (IND)-enabling studies indicated that WP1066 had minimal toxicity and no dose-related changes in mean body weight or in group means of hematologic or chemical parameters in doses up to 200 mg/kg in canines. Mean peak plasma concentrations achieved using a preclinical dose of 40 mg/kg was 4.31 μM. When WP1066 is delivered i.v. at a dose of 40 mg/kg, the mean concentration of WP1066 within the brain of mice with an intact blood–brain barrier (BBB) was 162 μM at 15 min and 6 μM at 6 h – concentrations that exceed those necessary for in vitro anti-tumor and immune-modulatory activities. WP1066 can still be detected within orthotopic brain tumors at concentrations of 2.3 μM (range: 0.52–4.0) three weeks after the last administration. The therapeutic effects of WP1066 are partially ablated by in vivo depletions of CD4 and CD8 T cells or in immunocompromised animal subjects [23,25]. A methylcellulose-based oral nanoparticle formulation was devised to increase serum half-life since the lipophilic properties of the drug precluded standard intravenous formulation with sufficient bioavailability. The oral bioavailability of WP1066 is approximately 30%.

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#95

Blocking IL-11 may help to regenerate diseased kidneys while being “safe for long-term use”:

“We found that IL-11 is detrimental to kidney function and triggers the development of chronic kidney disease," said Cook. “We also showed that anti-IL11 therapy can treat kidney failure, reverse established chronic kidney disease, and restore kidney function by promoting regeneration in mice, while being safe for long term use.”

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#96

According to DNA

3 ingredients that have been shown to assist with IL-11 are quercetin, sulforaphane and berberine.

Quercetin has been shown to possess anti-inflammatory and anti-fibrotic properties. It can inhibit the activation of STAT3, which is a key pathway in IL-11 signalling.

Berberine has demonstrated anti-inflammatory effects and the ability to inhibit various cytokines and signaling pathways, impacting IL-11.

Sulforaphane is known for its anti-inflammatory properties and its ability to inhibit the activation of NF-κB and STAT pathways, which are involved with IL-11.

This info provided by a supplement company so take it with a grain of salt.

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#97

β-Caryophyllene oxide (Found in Guava and Oregano), and falcarinol (Present in carrots, Panax ginseng, and Parsnips) also down regulate STAT3.

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#98

You could take galantamine too.

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#99

Screen Shot 2024-07-27 at 12.17.45 PM
Screen Shot 2024-07-27 at 12.17.45 PM962×588 48.5 KB

Source: x.com

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#100

Results from a quick research of pubmed on potential repurpose of current drugs for IL-11 downstream (rapamycin and lithium):

Screenshot 2024-07-30 at 11.24.03 AM
Screenshot 2024-07-30 at 11.24.03 AM1616×1020 67.8 KB

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#101

A commentary by Richard Miller (of the ITP) on this research. If anyone has access to the full article, please post:

Blocking an inflammatory protein slows the pace of ageing

Mice live longer and healthier lives when a cytokine protein called IL-11 is inhibited. The findings show how researchers can move beyond broad generalizations to engage with the nuances that modulate the pace of ageing.

https://www.nature.com/articles/d41586-024-02300-0

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#102

Blocking an inflammatory protein slows the pace of ageing.pdf (139.7 KB)

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#103

I hope someone will have the oppertunity to ask Stuart about the effect of IL-11 on epigenetic clocks.

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#104

“Viewed from a great distance, Earth appears as
a pale blue dot(1). It is only at a closer scale that
interesting details emerge, such as mountains
and cities.”

Love it…especially the (1) reference to Carl Sagan…that’s like shouting “We ARE Scientists! (COSMIC!)”

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