A study by researchers from the Medical Research Council and Imperial College London showed that blocking the IL-11 protein in mice extended their lifespan by up to 25%. The treatment reduced signs of ageing and the incidence of cancer, suggesting potential applications for human ageing, and is already undergoing clinical trials. Credit: SciTechDaily
Inhibiting IL-11 in mice extends lifespan and reduces signs of aging, potentially having implications for treating aging in humans.
Researchers from the Medical Research Council’s Institute of Medical Sciences said: Imperial College London Researchers have found that by “turning off” a protein called IL-11, they can extend the healthy lifespan of mice by nearly 25%. Working with colleagues at Duke-NUS Medical School in Singapore, they created mice lacking gene-produced IL-11 (interleukin 11) and tested the effects of IL-11. The mice’s lifespan was extended by an average of more than 20%. The researchers then treated 75-week-old mice (equivalent to about 55 years in humans) by injecting them with an anti-IL-11 antibody, a drug that blocks the effects of IL-11 in the body.
Promising results from anti-IL-11 treatment
According to a recently published study, NatureThe researchers found that administering the anti-IL-11 drug from 75 weeks of age until death extended the average lifespan of male mice by 22.5% and female mice by 25%. Treated mice lived an average of 155 weeks, compared with 120 weeks for untreated mice.
The treatment significantly reduced cancer mortality in animals, as well as mitigating many of the diseases caused by fibrosis, chronic inflammation, and poor metabolism that are hallmarks of ageing, with minimal observed side effects.
Video showing knockout mice that do not produce IL-11 (left) and normal aging mice (90-95 weeks old) (right). Credit: MRC Institute of Medical Research/Duke-NUS School of Medicine
“These findings are really exciting – treated mice had less cancer and did not show common signs of ageing and frailty, but also saw less muscle wasting and better muscle strength – in other words, the older mice given anti-IL11 were healthier,” said co-corresponding author Professor Stuart Cook of the UK Medical Research Council Laboratory of Medical Sciences (MRC LMS), Imperial College London and Duke-NUS School of Medicine in Singapore.
“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.”
Historical and future perspectives of IL-11 research
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.”
Professor Stuart Cook. Photo courtesy of the MRC Institute of Medical Research.
“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.”
Tackling global health issues with new knowledge
Scientists have previously argued that while IL-11 is essential for limb regeneration in some animals, it is an evolutionary leftover in humans. seedIL-11 is thought to be largely unnecessary in humans, but people make more IL-11 after age 55, and previous studies have linked it to 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 called multimorbidity and encompasses a range of conditions, including lung disease. Cardiovascular diseasediabetes, loss of vision and hearing, and many other diseases.
“In mice, IL-11 gene activity increases with age in all tissues. When this gene is activated, it causes a multi-disease state that is associated with aging and loss of function throughout the body, from vision to hearing, muscle to hair, and the pumping function of the heart to the kidneys,” Cook said.
According to many leading health organisations, including the NHS and WHO, multimorbidity and frailty are recognised as one of the greatest global healthcare challenges of the 21st century. Currently, there is no cure for multimorbidity, only treating the multiple underlying causes individually.
The scientists caution that the results of this study are in mice, and the safety and effectiveness of these treatments in humans needs to be further established in clinical trials before considering using anti-IL-11 drugs for this purpose.
Reference: “Inhibition of IL-11 signaling extends mammalian healthspan and lifespan,” Anissa A. Widjaja, Wei-Wen Lim, Sivakumar Viswanathan, Sonia Chothani, Ben Corden, Cibi Mary Dasan, Joyce Wei Ting Goh, Radiance Lim, Brijesh K. Singh, Jessie Tan, Chee Jian Pua, Sze Yun Lim, Eleonora Adami, Sebastian Schafer, Benjamin L. George, Mark Sweeney, Chen Xie, Madhulika Tripathi, Natalie A. Sims, Norbert Hübner, Enrico Petretto, Dominic J. Withers, Lena Ho, Jesus Gil, David Carling, Stuart A. Cook, July 17, 2024, Nature.
DOI: 10.1038/s41586-024-07701-9
The study was primarily funded by the National Medical Research Council (Singapore) and the Medical Research Council (UK).
