New Groundbreaking Study Shows 24% Lifespan Extension By Blocking IL-11
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- Опубліковано 5 вер 2024
- Here we look through the recent study showing the lifespan and healthspan extending effects of inhibiting IL-11, either genetically or therapeutically with an anti-body.
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Inhibition of IL-11 signalling extends mammalian healthspan and lifespan
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#IL11 #lifeextension #healthspan
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BCAA restriction at below 8 grams, or protein restriction at 5-8% keeps me going on top of high dose Alpha lipoic acid. K2 MK7, D3 Megadosing and magnesium bisglycinate since it plays a important role in BCAA catabolism with glycine and both magnesium. My BHB ketones could be at 3-6 mmol. maybe 1.5 mmol if i do some targeted carbs at 60 grams with glass noodles. Screw senescent cells accumulating BCAAs and the age related chronic activation of mTOR and the role of elevated serum BCAAs in obese humans and animals and elderly sarcopenic muscle. Add in pro-metabolic saturated fat while avoiding anti metabolic MUFA and eliminating PUFA as much as possible to 3% of energy intake. (80% fat from coconut and dairy 4-8% protein and 0-10% Potato or glass noodle mung bean carbs) - Low protein/Classical Keto targeted SFA based Sprinter
Richard, thanks for the review. This paper is important for longevity!
Lamming Lab has also been doing critical ground breaking research with BCAA restriction/low protein diets and the role of hyperactivated MTOR in elderly humans, obese humans and animals alike. - Low protein/BCAA restricted targeted keto sprinter
Hi Ray, thanks. I agree!
Thanks Richard. Since I don't have time to do this stuff myself, I appreciate the good work that you do.
Hi Jonny thanks! I hope that you find the reviews useful!
Research paper reviews are very productive even if they spawn more questions. Thanks!
Controlling IL-11 seems like another reason to keep systemic inflammation low. Maybe mapping out what's upstream of IL-11 can help clarify potential lifestyle interventions. Also, as IL-11 is part of the IL-6 family of cytokines I wonder if tracking IL-6 (blood test) can provide insight into IL-11. Low IL-6 is a good marker on its own.
I wonder if CoQ10 would have an impact on IL-11 then. It’s currently the only supplement (that I’m aware of) that has a substantial effect on IL-6.
Hi Peter, thanks for sharing. It is an area I need to investigate more!
I've read that the leading cause of natural death in aged lab mice is cancer. Did the report provide any data on cause-of-death of the treated mice? The reason I'm asking is that perhaps inhibiting IL-11 in old-aged mice might have delayed development of cancer, thereby extending lifespan. Just curious, since that might point to IL-11 inhibition as a potential strategy in treating or preventing cancer.
A casual google scholar search shows a numerous papers that found IL-11 encouraged the growth and survival of various types of cancer. Common sense tells us this is probably the underlying reason for the life extension in mice.
Hi Rob, thanks for the question. In the paper they don't directly address this that I can see, but they did perform autopsies on the mice and look for cancer. Here is what they said "Cancers are a common cause of death in old mice44, and gross autopsy data revealed fewer macroscopic tumours in mice with Il11 deletion (pooled sexes: wild-type, 49 out of 84 mice had tumours; Il11−/−, 3 out of 25 mice had tumours; P
As mentioned elsewhere in the comments, Omega 3 fats can inhibit IL-11.
I remember reading that the painkiller Indomethacin is also a potent IL-11 blocker.
The anti inflammatory dexamethasone blocks IL-11 too.
Likely we can find other natural compounds and synthetic anti inflammatories that reduce IL-11 activity.
Hi guys, the most effective way to inhibit IL-11 with a supplement is currently fish oil, it also inhibits IL-6
Confirmed:
Liu Y, Lin J, Chen Y, Li Z, Zhou J, Lu X, Chen Z and Zuo D: Omega‑3 polyunsaturated fatty acids inhibit IL‑11/STAT3 signaling in hepatocytes during acetaminophen hepatotoxicity. Int J Mol Med 48: 190, 2021
Do you no the dosage ?
Don’t take too much .ll it is a blood thinner
@paulwolf3302 take care of your diet and then ultimately it is upto the Lord … when it is time to it is time to go
I haven't seen any study that shows that fish oil lowers IL-11. Only the effect of IL-6 have been shown. It's not the same. One IL type may go up while another may go down with any given supplement.
If you follow this flawed logic, curcumin and green tea would also do it.
It looks quite promising and perhaps available in the not too distant future? Thank you for this excellent review Richard 👌
Fish oil already does that:
Liu Y, Lin J, Chen Y, Li Z, Zhou J, Lu X, Chen Z and Zuo D: Omega‑3 polyunsaturated fatty acids inhibit IL‑11/STAT3 signaling in hepatocytes during acetaminophen hepatotoxicity. Int J Mol Med 48: 190, 2021
Hi Pierre, thank you! It is in human trials, so hopefully not too far away. It might also spawn more research on IL-11 that could lead to other ways of inhibiting it.
@@ModernHealthspan 🤞I saw (on YT) some days ago the conference of Professor Alessio on the Longevity Summit in Dublin from past month where she was presenting her research about the also very promising benefits of supplementing with D-limonene, who's interacting with cytokine IL-6. IL-11 is a cytokine that belongs to the IL-6 family of cytokines, so maybe D-limonene could indirectly play a role in IL-11 expression ?
The IL-11 pathway diagram shows that IL-11 inhibits LKB1 which would normally decrease MTOR, therefore inhibiting it indirectly raises MTOR. Took me a minute to get my head around that.
Yes, net effect of the therapy seems to be to inhibit MTOR.
Why not take Rapamycin to inhibit mTOR?
Hi Ken, thanks for sharing. Yes, there was more detail on the pathway in the paper and other sources but I was concerned it would get too much into the weeds if I went through all the steps. You are correct LKB1 and stopping it inhibiting mTOR is a key part of the process.
@@ModernHealthspan I think the flowchart says the opposite and that the net effect of inhibiting IL-11 is to inhibit MTOR. Note that other therapies strive to inhibit MTOR. Reading the flowchart: IL-11 inhibition reduces the inhibition of LKB1, so raises LKB1 and AMPK. Then more AMPK increases the inhibition of MTOR.
Thank you for all your doing , wish you well also
Hi Ashley, thank-you!
It is virtually unheard of for something that raises body temperature to increase lifespan. Almost all the life extension interventions that work in mice lower their body temperature.
Babies are warm and dead people are cold…
@@2piecesofwood1pieceofrope Scripps Institute scientists modified mice to decrease their body temp 0.3-0.5 degrees in 2006. Result: median lifespan was extended about 20 percent in females and about 12 percent in males. Other scientists checked other possibilities for the result. Not metabolism. Can't remember the other possibility, but it was ruled out too. The change in temperature is what lengthened their lives.
It is known that calorie restriction reduces body temperature. Metformin, berberine, rapamycin... all lower mouse body temp.
Babies feel warm because of brown fat. As we age, we lose most of that, which is why a draft can hurt. There is evidence that we can grow brown fat by ice bath submersion. I don't know how valid that research is. Maybe people with less brown fat just quit the experiments.
Have you not heard of the BCAA restriction studies from Lamming Lab? -Low protein/BCAA restricted targeted keto sprinter
Hi thanks for sharing. I need to think about this. BMR (basal metabolic rate) goes down with age, so you would think a higher BMR would imply a younger phenotype.
@@ModernHealthspan Or combine alpha lipoic acid with BCAA restriction? Without impaired BCAA catabolism clogging up the mitochondria, you massively boost thermogenesis that way.
OK but what supplements can you take for this?!
AI generated response:
Curcumin:
Curcumin, the active compound in turmeric, has been found to inhibit the production and signaling of IL-11 in various studies.
Curcumin can suppress the expression of IL-11 and its downstream signaling pathways, which may have potential therapeutic applications in conditions associated with elevated IL-11 levels.
Resveratrol:
Resveratrol, a polyphenol found in red wine and other plants, has been shown to inhibit the production and signaling of IL-11.
Resveratrol can downregulate the expression of IL-11 and disrupt its signaling cascade, leading to reduced IL-11-mediated effects.
Green tea polyphenols:
Compounds in green tea, such as epigallocatechin gallate (EGCG), have been observed to inhibit the production and activity of IL-11.
Green tea polyphenols can modulate the expression and signaling of IL-11, which may contribute to their anti-inflammatory and potential therapeutic properties.
Omega-3 fatty acids:
Omega-3 fatty acids, such as those found in fish oil, have been reported to inhibit the production and signaling of IL-11.
The anti-inflammatory effects of omega-3 fatty acids may be partly mediated through their ability to suppress IL-11 levels and signaling.
Fish oil:
Liu Y, Lin J, Chen Y, Li Z, Zhou J, Lu X, Chen Z and Zuo D: Omega‑3 polyunsaturated fatty acids inhibit IL‑11/STAT3 signaling in hepatocytes during acetaminophen hepatotoxicity. Int J Mol Med 48: 190, 2021
Not sure if this would work but CoQ10 can lower IL-6 and IL-11 is in the IL-6 cytokine family. There is evidence that CoQ10 can act synergistically with cancer therapy but the mechanism isn’t understood- it’s possible it could be reducing IL-11, which is pro-cancerous.
Also keep in mind that IL-11 reduction is going to have more impact on mice since they are far more likely to die of cancer.
Hi thanks for the question. And thanks to Roger and Elder for their responses. At the moment fish oil seems to be the favourite.
@@ModernHealthspan In humans, fish oil generally does not seem to reduce all cause mortality, at least according to a physionic review of the literature. Therefore, it may not be an effective therapy for extending lifespan in humans.
I think this is confusing. It's not lifespan extension. It's disease prevention. Because if if you eliminate all diseases you won't live longer than the natural lifespan maximum that is estimated to be 120 years old. If anyone can pass that it would be something new
Great review, thank you
Mice is one thing, we need human studies.
Hi thanks for your comment. This is true. There are on-going human trials for fibrosis so hopefully we will know more soon, at least the effects on the health biomarkers.
Lamming Lab studies and the BCAA restriction studies disagrees. - Low protein/Classical Keto SFA based targeted sprinter
Great thumbnail and news
Very interesting! Thanks!
Much of the effects from blocking IL-11 probably stems from the fact that it also inhibits mTOR. Taking rapamycin or fasting should provide similar results
how do you inhibit IL-11 ??
Omega-3 from krill oil.
Yes good health to you!I think the next 5-10 years they will be able to increase life span 20 years with a supplement but the life span will increase as new therapies and break throughs happen.
Is there a study in another mammal than mice with IL-11 blocking? iam always a bit sceptic when i hear "in mice" :)
So where does that leave us ? Should we be supplementing AMPK ?
Hi Mike, thanks for the question. Activating AMPK is generally a "good thing" so that sounds like something to do.
Call physionic
Do you suspect blocking IL-11 might extend life of people with shorter telomeres, but be less effective on those with longer telomeres?
Thanks Richard.
Hi Ron, thanks!
can i replace the fishoil for alges instead they have the omega 3 I am vegan ? Thank You
Not the same. Omega-3 from krill oil.
@@williammorgan7769 only option as am vegan 🙂
If IL-11 is part of SASP toxin emissions from senescent cells and IL-11 goes up along with senescence in aging, then my senolytic supplements will help.
Omega-3 from krill oil.
Is x203 a known substance or something proprietary and under wraps?
There was once a satirical comedy program on British TV called Never Mind the Quality; Feel the Width. As an old geezer, take it from me: there is no fun in prolonged decrepitude.
ok then, why dont you stop making youtube comments and end it all? also lost on you is the term 'healthspan'
We will eventually be able to treat that though.
if it inhibits MTOR then your going to heal and repair yourself slower correct?
Very interesting
How is this paper related to Altos Labs?
Ruchard how do we get the product?
Hi Kenneth, thanks for the question. X203 is an experimental antibody at the moment and not available for sale. There may be other substances which can inhibit IL-11. I need to investigate this more.
Omega-3 from krill oil.
Is their a supplement that inhibits IL-11 an what would the dosage be ?
Hi thanks for your question. I have not had time to investigate this enough. It is on my list and I will make a video when I have done this. However I do see other commentators suggesting fish oil, with omega-3 fats.
Omega-3 from krill oil.
Well those who think that we will be able to bring substantial increase in average and maximum lifespan just by oral supplements are wrong sadly.
At one moment,we will have to go to more aggressive routes like injections and or intravenously.
Hi Matt, thanks for your comment. I completely agree. It seems to me that we can tweak things with supplements (though lifestyle is one of the biggest levers) but for a substantial increase we will need something like partial reprogramming or E5/exosomes (or something completely new) to work reliably. BTW, the IL-11 intervention is an injection.
@@ModernHealthspan and yet currently the most powerful intervention we have is in the form of a little pill called rapamycin
Who knows
Anything is possible
You should be careful in making such sweeping statements.
You've no idea what advancements may come in packaing of oral supplements and modification of the gut lining and microbiome.
Also most normal people have no access to anything but oral and topical supplementation.
Also it really depends on what you mean by "substantial" - a 100% increase in lifespan? A 20% increase? A 5% increase? what?
Does this mean we should cut done on protein and/or fast more often as we get older.
It is mainly animal protein that tends to raise MTOR, so you could just switch to plant protein... eat more beans and veggies and less meat.
Lets find a medicine to prevent Alzheimer and other brain demolishing diseases.
Mice and cell cultures . . .😢
And maybe this will work in people and maybe not. In any case, I'm sure we're a long way off from actual human testing.
It's already being tested in humans
@@unutilisateur4729 really? By whom and where?
@@jontpt Can't find it right now, but to be clear, this isn't a trial targeting aging, this is for a specific condition.
@@unutilisateur4729 what is the specific condition? I thought this stuff is supposed to extend lifespan by 25%?
@@jontpt I don't know if UA-cam would allow me to post a link so just Google that: Boehringer Ingelheim begins clinical development of first-in-class treatment for fibrotic diseases
Ingelheim, Germany and Singapore, Tue, 05/09/2023 - 12:00
Unless u can extend my 20-40’s, I’ll pass. No one wants to be old n feeble. Post 80 is just waiting to die, dont want 25 years in a waiting room or being too old to do anything.
That's the idea cupcake
Life is too expensive to live 24% longer. You’ll have to work until you’re 80 to retire. That’s why the Controllers are keeping us sick and on pharmaceuticles.
Given that death is inevitable; what is this obsession with living longer? Why not become enlightened and awakened to your spirit beyond the death of the body? Buddha, Ramana Maharshi, Ramakrishna did not suggest living forever; they suggested waking up to the illusion of experience and your true nature as beingness itself. The fear of death has a stench; and all the great beings in history challenged within themselves to awaken by facing this fear and accepting their death utterly and finding in that great profound peace and awakening. Why not be healthy and live long certainly; but to turn it in to an obsession denies the inevitable fact that we all die; even jack la lane; even richard simmons; even if you live to be 120 in a wheelchair, then you'll die and discover your eternal deathless spirit.
chilling thought
"Why not be healthy and live long certainly". That's exactly what longevity is all about. Why don't people understand this?
Hi David, thanks for your comment. The primary aim is healthspan, being healthy for longer. This has a side effect of living longer (generally). Most of the paper and video were concerned with healthspan and what we cover on the channel is the same. My focus is not driven by a fear of death but by a desire to be healthy and able to make the most of my life for as long as I can.
@@robbertag808 People don't care until Visceral fat is staring at them. - Low protein/BCAA restricted targeted keto sprinter
Dead right! I see only diminishing returns after the late 70s.