summary: Researchers have found that blocking the protein IL-11 extends the lifespan of mice by up to 25%. The treatment also reduces cancer and age-related diseases. This groundbreaking discovery could potentially lead to anti-aging treatments for humans in the future. Further clinical trials are needed to confirm safety and efficacy.
Key Facts:
- Life Extension: Blocking IL-11 extends mouse lifespan by 25%.
- Health Benefits: A reduction in cancer and age-related diseases was observed.
- Future possibilities: Currently undergoing clinical trials, it could potentially lead to anti-aging treatments for humans.
sauce: UK Research and Innovation
Scientists from the Medical Research Council’s Institute of Medical Sciences and Imperial College London have found that ‘switching off’ a protein called IL-11 can significantly extend the healthy lifespan of mice by around 25%.
The scientists, working with colleagues at Duke-NUS Medical School in Singapore, tested the effects of IL-11 (interleukin 11) in mice lacking the gene that produces it, which extended the mice’s lifespan by an average of more than 20%.
The researchers also treated 75-week-old mice (equivalent to about 55 human years) with injections of an anti-IL-11 antibody, a drug that blocks the action of IL-11 in the body.
Result is, NatureThe results were dramatic: the average lifespan of mice treated with the anti-IL-11 drug from 75 weeks of age until death was increased by 22.4% in males and 25% in females, to 155 weeks, compared with 120 weeks for untreated mice.
The treatment significantly reduced cancer mortality in the animals, as well as mitigating many of the diseases caused by fibrosis, chronic inflammation, and metabolic decline that are hallmarks of ageing, with minimal observed side effects.
Co-corresponding author Professor Stuart Cook from the UK Medical Research Council Institute of Medical Sciences (MRC LMS), Imperial College London and Duke-NUS Medical School in Singapore said: “The results of this study are very exciting. Treated mice had less cancer and did not show common signs of ageing and frailty, but we also saw less muscle wasting and improved muscle strength. In other words, old mice given anti-IL11 were healthier.”
“Life-extending drugs and treatments proposed to date have had adverse side effects, been ineffective in both men and women, or were able to extend life but not healthy lifespan, but this does not seem to be the case with IL-11.”
“Although these findings were only made in mice, they raise the intriguing possibility that this drug might have a similar effect in older people. Anti-IL-11 treatments are currently in clinical trials for other diseases, which could provide exciting opportunities to study their effects in older people in the future.”
Researchers have been studying IL-11 for many years and in 2018 were the first to show that IL-11 is a pro-fibrotic and pro-inflammatory protein, overturning its long-standing mischaracterization as anti-fibrotic and anti-inflammatory.
Co-corresponding author Assistant Professor Anissa Wijaya from Duke-NUS Medical School in Singapore said: “This project began in 2017 when our collaborator sent us tissue samples for another project. Out of curiosity, we ran some experiments to look at IL-11 levels. The measurements clearly showed that IL-11 levels increased with age, which really got us excited.”
“We found that these elevated levels contribute to adverse effects in the body, such as inflammation and the inhibition of organ healing and regeneration after injury. Although our study was conducted in mice, we have seen similar effects in studies of human cells and tissues, so we are hopeful that these findings will be highly relevant to human health.”
“This study is an important step towards a deeper understanding of aging, and we have demonstrated in mice a treatment that has the potential to extend healthy aging by reducing frailty and the physiological signs of aging.”
Previously, scientists had hypothesized that IL-11 was an evolutionary vestige in humans because it is essential for limb regeneration in some animal species but is thought to be largely dispensable in humans.
However, in humans, IL-11 production increases after age 55, and previous studies have shown that this is associated with chronic inflammation, organ fibrosis, metabolic disorders, muscle wasting (sarcopenia), frailty, and cardiac fibrosis – many of the symptoms associated with aging.
When an individual has two or more such conditions, it is known as multimorbidity and encompasses a range of conditions including lung disease, cardiovascular disease, diabetes, vision and hearing loss, and many more.
Professor Cook said: “IL-11 gene activity increases in all tissues as mice age. When this gene is activated it causes multimorbidity, a condition that is associated with ageing and decline throughout the body, from vision to hearing, muscle to hair, and the pumping ability of the heart to the kidneys.”
Multimorbidity and frailty are recognised as one of the greatest global healthcare challenges of the 21st century, according to many leading health organisations, including the NHS and WHO.
Currently, there is no cure for multimorbidity other than treating the multiple underlying causes individually.
The scientists caution that the results of this study are in mice, and that the safety and efficacy of these treatments in humans needs to be further established in clinical trials before considering using anti-IL-11 drugs for this purpose.
Funding: The study was primarily funded by the National Medical Research Council (Singapore) and the Medical Research Council (UK).
About this research news on inflammation and longevity
author: Hilary Jones
sauce: UK Research and Innovation
contact: Hilary Jones – UK Research and Innovation
image: Image courtesy of Neuroscience News
Original Research: Open access.
“Inhibition of IL-11 signaling extends mammalian healthspan and lifespan” by Stuart Cook et al. Nature
Abstract
Inhibition of IL-11 signaling extends mammalian healthspan and lifespan
With regard to healthspan and longevity, ERK, AMPK, and mTORC1 represent key pathways, with inflammation being a centrally important feature.
Here, we investigated whether IL-11, a proinflammatory cytokine of the IL-6 family, has a detrimental effect on age-related diseases and longevity.
As mice age, IL-11 increases across cell types and tissues and regulates the ERK-AMPK-mTORC1 axis to orchestrate aging pathology at the cellular, tissue, and organismal levels.
delete Ile 11 or Il11ra1 Prevents metabolic decline, multiple diseases, and frailty in old age.
Treatment of 75-week-old mice with anti-IL-11 for 25 weeks improved metabolism and muscle function and reduced biomarkers of aging and frailty in both sexes. Ile 11 It extended the lifespan of both male and female mice by an average of 24.9%.
Treatment with anti-IL-11 from 75 weeks of age until death extends the average lifespan of male mice by 22.5% and female mice by 25%. Taken together, these results indicate that the proinflammatory factor IL-11 plays a role in mammalian healthspan and longevity.
We believe that anti-IL-11 therapies, currently in early clinical trials for fibrotic lung diseases, may provide a translational opportunity to determine the effect of IL-11 inhibition on aging pathologies in elderly patients.
