Blocking IL-11 protein extends lifespan and health in mice by 25%, study finds

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 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.

“These findings are very exciting. The treated mice had less cancer and did not show the typical signs of aging and frailty, but they also showed less muscle wasting and improved muscle strength. In other words, the old mice that received anti-IL11 were healthier.”

The life-prolonging 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 obtained only in mice, they raise the intriguing possibility that this drug might have similar effects in elderly humans. Anti-IL-11 treatments are currently in clinical trials for other diseases, which could provide exciting opportunities to study its effects in elderly humans in the future.”

Co-corresponding author Professor Stuart Cook of the Medical Research Council's Institute of Medical Sciences (MRC LMS), Imperial College London and Duke-NUS School of Medicine in Singapore

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, as we have demonstrated a potential treatment in mice that could 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: “In mice, activity of the IL-11 gene increases with age in all tissues. When this gene is activated it causes multimorbidity – diseases associated with ageing and loss of function 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.

The study was primarily funded by the National Medical Research Council (Singapore) and the Medical Research Council (UK).