Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. (Widjaja, Cook, et al 2024)

A drug has increased the lifespans of laboratory animals by nearly 25%, in a discovery scientists hope can slow human ageing too.

The treated mice were known as "supermodel grannies" in the lab because of their youthful appearance.

They were healthier, stronger and developed fewer cancers than their unmedicated peers.

The drug is already being tested in people, but whether it would have the same anti-ageing effect is unknown.

The quest for a longer life is woven through human history.

However, scientists have long known the ageing process is malleable - laboratory animals live longer if you significantly cut the amount of food they eat.

Now the field of ageing-research is booming as researchers try to uncover - and manipulate - the molecular processes of ageing.

The team at the MRC Laboratory of Medical Science, Imperial College London and Duke-NUS Medical School in Singapore were investigating a protein called interleukin-11.

Levels of it increase in the human body as we get older, it contributes to higher levels of inflammation, and the researchers say it flips several biological switches that control the pace of ageing.

Longer, healthier lives
The researchers performed two experiments.

• The first genetically engineered mice so they were unable to produce interleukin-11
  
  
• The second waited until mice were 75 weeks old (roughly equivalent to a 55-year-old person) and then regularly gave them a drug to purge interleukin-11 from their bodies
  

The results, published in the journal Nature,, external showed lifespans were increased by 20-25% depending on the experiment and sex of the mice.

Old laboratory mice often die from cancer, however, the mice lacking interleukin-11 had far lower levels of the disease.

And they showed improved muscle function, were leaner, had healthier fur and scored better on many measures of frailty.

I asked one of the researchers, Prof Stuart Cook, whether the data was too good to be believed.

He told me: "I try not to get too excited, for the reasons you say, is it too good to be true?

"There's lots of snake oil out there, so I try to stick to the data and they are the strongest out there."

He said he "definitely" thought it was worth trialling in human ageing, arguing that the impact "would be transformative" if it worked and was prepared to take it himself.


https://www.bbc.co.uk/news/articles/cv2gr3x3xkno

 

So first I need a drug to cure ME then a drug that can make me live another 20 years so I can make up for the years lost to this illness. Imagine!

Something a bit scary in a sci-fi kind of way about the potential implications of a life extending drug though.

 

Disabled people like us on limited income are likely the last who will have access to those drugs unfortunately. (Given both the political system, and the ableism that permeates healthcare.)

 

Yep, that's one of the things that makes it feel scary and dystopian.

 

2024 Jul 17. doi: 10.1038/s41586-024-07701-9. Online ahead of print.
Inhibition of IL-11 signalling extends mammalian healthspan and lifespan
Anissa A Widjaja # 1 , Wei-Wen Lim # 2 3 , Sivakumar Viswanathan 2 , Sonia Chothani 2 , Ben Corden 3 4 , Cibi Mary Dasan 2 , Joyce Wei Ting Goh 2 , Radiance Lim 2 , Brijesh K Singh 2 , Jessie Tan 3 , Chee Jian Pua 3 , Sze Yun Lim 2 , Eleonora Adami 5 , Sebastian Schafer 2 , Benjamin L George 2 , Mark Sweeney 6 , Chen Xie 3 , Madhulika Tripathi 2 , Natalie A Sims 7 8 , Norbert Hübner 5 9 10 , Enrico Petretto 2 11 , Dominic J Withers 6 12 , Lena Ho 2 , Jesus Gil 6 12 , David Carling 6 12 , Stuart A Cook 13 14 15
Affiliations

• PMID: 39020175
• DOI: 10.1038/s41586-024-07701-9

Abstract
For healthspan and lifespan, ERK, AMPK and mTORC1 represent critical pathways and inflammation is a centrally important hallmark1-7. Here we 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.

 

Results here are pretty striking. Will be interesting to see how it pans out in humans if they try it for fibrotic lung disease.

However the thing about ageing research in people is it takes a long time to collect data!





Still I'm very excited about ageing research because it seems to cut across health conditions. There are a lot of problems we are more prone to as we age. For example, as they make huge progress on cancer, it just feeds more people into the maw of dementia. I read that curing cancer would lift average lifespans only by some small amount, two or 3 years. Because ageing is about all our defences breaking down. Identifying the underlying process of ageing, if there is one, would allow us to make big progress in delaying disease.

From what i read, they think DNA methylation profiles are correlated with ageing. Long-lifespan animals like cockatoos and tortoises have different DNA methylation profiles than shorter-lifespan animals, like mice. That's just an observation for now, but it opens up the possibility for intervention.

They're also carving up the anti-ageing space into two parts. 1. extending potential lifepsan, i.e. moving out the maximum age a person can live to, vs 2. extending actualised lifepsan, the amount of the theoretical maximum we get, which is more akin to diet and exercise advice, etc. traditional healthcare. This study looks like that latter kind of intervention.

 

I should add that not only are the benefits visible in mice engineered to be low in IL-11 but also in mice given anti-IL-11 therapy once they were already old.

 

This is the drug.

To achieve this goal, we administered a neutralizing IL-11 antibody (X203) or IgG control to aged mice and studied healthspan indices29,38(Fig. 3a).


Anyone know what X203 is?

 

This is the Nature paper underlying multiple articles about "supermodel granny" mice. Eg 'Supermodel granny' drug extends life in animals (BBC News)

 

In the most excitable parts of the longevity research community they talk about "escape velocity". You live long enough to be there once the anti-ageing drugs begin accumulating fast enough that you don't die!

It's not realistic, but there's a germ of truth to it, and you can see it in the cystic fibrosis community. 50 years ago they died as kids, then as teens, then as young adults and now with trifakta they can expect normal lifespans. I read a heart-wrenching article about a girl with Cystic Fibrosis whose older sister died age 12 and she always thought she had a few years left but now she's facing the very unexpected and life-altering fact that she's actually ... fine?

I find the cystic fibrosis story very encouraging. Progress is possible!

 

It's an antibody, available to researchers. Quite expensive at $1486 for a milligram:

https://www.antibodysystem.com/product/8926.html

Perhaps one day everyone over 50 will be taking it each morning alongside their fish oil and celebrex and statins!

 

Absolutely, the CF community fundraised billions of dollars privately to get there. There are no miracles.