Inhibition of IL-11 signalling extends mammalian healthspan and lifespan- Nature
Female Il11-deleted mice are protected from age-associated obesity, frailty, and metabolic decline. Male mice lives 22.5% longer and female mice 25% longer.
The effects were similar to rapamycin but had less negative effects on liver and other organs when rapamycin is used for extended times.
For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark. Here they examined whether IL-11, a pro-inflammatory cytokine of the IL-6 family, has a negative effect on age-associated disease and lifespan. As mice age, IL-11 is upregulated across cell types and tissues to regulate an ERK–AMPK–mTORC1 axis to modulate cellular, tissue- and organismal-level ageing pathologies. Deletion of Il11 or Il11ra1 protects against metabolic decline, multi-morbidity and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improves metabolism and muscle function, and reduces ageing biomarkers and frailty across sexes. In lifespan studies, genetic deletion of Il11 extended the lives of mice of both sexes, by 24.9% on average. Treatment with anti-IL-11 from 75 weeks of age until death extends the median lifespan of male mice by 22.5% and of female mice by 25%. Together, these results demonstrate a role for the pro-inflammatory factor IL-11 in mammalian healthspan and lifespan. We suggest that anti-IL-11 therapy, which is currently in early-stage clinical trials for fibrotic lung disease, may provide a translational opportunity to determine the effects of IL-11 inhibition on ageing pathologies in older people.
The major signalling mechanisms that regulate lifespan across species include ERK, STK11 (also known as LKB1), AMPK, mTORC1 and IGF1–insulin modules. These pathways are collectively perturbed in old age to activate hallmarks of ageing, which include mitochondrial dysfunction, inflammation and cellular senescence1. In aged organisms, the AMPK–mTORC1 axis is uniquely important for metabolic health, with notable effects in adipose tissue and therapeutic inhibition of mTOR extends lifespan in mice.
Ageing studies to date have focused largely on lifespan extension, particularly in yeast, worms and fruit flies, but lifespan extension does not necessarily reflect longer healthspan. There is a need for integrated studies to determine the effects of interventions on both healthspan and lifespan. Laboratory mice are particularly suited for such experiments, as ageing pathologies that are important for human wellbeing and function are apparent and lifespan studies are well established in mice.
The importance of chronic sterile inflammation for ageing pathologies is increasingly recognized and inflammation itself is a central hallmark of ageing. In simplified terms, ageing is associated with a dysfunctional adaptive immune system that is characterized by immunosenescence and thymic involution along with inappropriate activation of innate immune genes such as IL-67. The pro-inflammatory signalling factors NF-κB and JAK–STAT3 are specifically implicated in ageing and JAK inhibitors can alleviate age-related dysfunction.
they proposed that IL-11, a pro-inflammatory and pro-fibrotic member of the IL-6 family, may promote age-associated pathologies and reduce lifespan.
Brian Wang is a Futurist Thought Leader and a popular Science blogger with 1 million readers per month. His blog Nextbigfuture.com is ranked #1 Science News Blog. It covers many disruptive technology and trends including Space, Robotics, Artificial Intelligence, Medicine, Anti-aging Biotechnology, and Nanotechnology.
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As IL-11 is downstream of TGF-beta’s role in fibrosis and H2S signaling keeps TGF-beta latent, it’s possible these lifespan effects are merely downstream of pathways like AMPK/FOXO/DAF-16. Has this been tested yet? (Also note the tradeoff you’d get in lifespan vs. fertility with blanket IL-11 inhibition; embryos wouldn’t implant. Interesting how this tradeoff keeps reappearing.)
N.B. that IL-6 signaling is also suppressed by H2S. Low H2S triggers IL-6 and then hepcidin to sequester iron.
The lowly ignorance medical science over keeps us in. They don’t tell us what inflammation is, per the medical medium information inflammation Is a result of toxins released from pathogenes in our body and harming its systems and organs especially the nerve system. Adopting a diet that Straightens your liver so it can better fight them is how fundamentally you reduce inflammation. They are hiding from us how our body work and sway our understanding of how our body works in order to keep us sick and alive. That’s how they keep making more money on us by giving us more medication and more medical treatment.
https://www.medicalmedium.com/blog/truth-about-inflammation
Straightens your liver? So like quack chiropractors for internal organ alignment?
Yeah, like they did to your brain. You probably don’t remember it.
True advances in Anti-aging will likely require Medical Tourism with locations that simultaneously allow significant, minimally-regulated experimentation -and- a modern, trustable governing system like the Charter City Prospera in Honduras – though it is unclear whether much of that original libertarian, ultra-tech, freedom-snadbox still exists.
Cool, humans will live 1% longer and healthier. Seriously, messing with pathways or with the creation of damage won’t do it, you need to reduce the damage. You can do all the gene therapies you want on humans, you will still die of old age, getting only an extra decade at best by combining everything you can, which is not feasible for the mass.
Plus gene therapies in vivo are way too expensive. Reducing damage will be much cheaper. First generation therapies developped by the likes of Cyclarity or Oisin will cost almost nothing, and will add 2 or 3 years or lifespan each.
Reducing damage is way easier, way cheaper, way less invasive, than messing with pathways or the creation of damage.
Unless you just have a soft spot for mice this is more likely to bear fruit for us Homo Sapiens:
“Human Age Reversal with TRIIM – XA Trial/ Dr Greg Fahy
Dr. Greg Fahy presents about the latest results from TRIIM-XA Trial in this video. In a significant advancement, researchers have successfully duplicated the outcomes of the inaugural human age-reversal trial. This replication bolsters the original findings, suggesting that treatments targeting thymus regeneration could be crucial in reversing certain aspects of aging. The TRIIM-X trial is an expanded pilot clinical study designed to assess a personalized combination treatment regimen for thymus regeneration. The thymus, a crucial component of the immune system, significantly deteriorates with age. Regenerating it may help prevent or reverse critical aspects of immunosenescence (the aging of the immune system) and potentially mitigate or reverse key elements of the aging process more broadly.
their website:
https://interveneimmune.com/ ”
https://www.youtube.com/watch?v=QvFycdA3osQ
Thanks for the tip. I wrote to Dr. Fahy since his website offers that option for interest in further trials, though he’s based in California so me in NYC might not be able to participate practically.
I wish they had done a larger trial, preferably double-blind because people might be doing other things to reduce their epigenetic clock while in the 1-year program to confound the results. Still, losing a net 1.5 years after 1 year of treatment is significant, especially if there are functional results as well.
I think they’re expanding the trials as fast and as much as funding permits.
I agree that this is the most promising thing going in HUMAN life extension at the moment. Most successful mouse therapies don’t work in humans, after all.
And Dr. Fahy’s approach is seriously scaleable. It doesn’t HAVE to be expensive.
Your welcome; can’t understand why he (Fahy) struggles to get the media attention/funding he deserves. I think the likely reason is that the 3 drug cocktail is already out there DHEA/HGH/Metformin; so no easily way for big pharma to patent the process. My understanding is that you have to pay to participate in the trial(s) to the tune of 12-15K/yr. Don’t know how long said trial would last maybe 1-2 yrs initially but don’t quote me. My biggest issue is that I live in Ohio and they are based in California. I don’t know if he/they have any authorized “satellite” programs in other States available.
help me, so can this gene editing be done in adults or only embryos?
Why would you do gene editing when they demonstrated in this very paper that pharmacological inhibition is sufficient and is already in phase I human trials?