In a new study, scientists at the Medical Research Council Laboratory of Medical Sciences and Imperial College London have discovered that “switching off” a protein called IL-11 can significantly extend the healthy lifespan of mice by nearly 25 percent.
The findings, published in Nature, suggest a promising avenue for anti-aging therapies in humans.
The research team, in collaboration with colleagues at Duke-NUS Medical School in Singapore, investigated the effects of IL-11 by creating mice that lacked the gene producing this protein. These genetically modified mice lived over 20 percent longer on average than their counterparts. Additionally, the team treated 75-week-old mice (comparable to 55-year-old humans) with an anti-IL-11 antibody, a drug designed to inhibit IL-11’s effects.
The results were remarkable: male mice extended their median lifespan by 22.4 percent and females by 25 percent, living an average of 155 weeks compared to 120 weeks for untreated mice.
“This study is very exciting,” said Professor Stuart Cook, co-corresponding author from the Medical Research Council Laboratory of Medical Sciences (MRC LMS), Imperial College London, and Duke-NUS Medical School. “The treated mice had fewer cancers, and were free from the usual signs of aging and frailty. We also saw reduced muscle wasting and improvement in muscle strength. In other words, the old mice receiving anti-IL-11 were healthier.”
The treatment reduced deaths from cancer and mitigated many diseases caused by fibrosis, chronic inflammation, and poor metabolism, which are hallmarks of aging. According to the researchers, very few side effects were observed.
IL-11, a pro-inflammatory cytokine, was previously thought to be anti-inflammatory. However, research by Professor Cook’s team in 2018 revealed its role in promoting fibrosis and inflammation. In this latest study, the researchers found that IL-11 levels increase with age, contributing to negative effects such as inflammation and preventing organs from healing and regenerating.
“This project started back in 2017 when a collaborator sent us some tissue samples for another project. From the readings, we saw that IL-11 levels increased with age, which was very exciting,” said assistant professor Anissa Widjaja, co-corresponding author from Duke-NUS Medical School. “We found that these rising levels contribute to negative effects in the body, such as inflammation and preventing organs from healing and regenerating after injury.”
In their experiments, the researchers demonstrated that genetic deletion of IL-11 or its receptor protected against metabolic decline, multimorbidity, and frailty in old age. Administration of anti-IL-11 to 75-week-old mice for 25 weeks improved metabolism, muscle function, and reduced aging biomarkers and frailty across both sexes.
“Previously proposed life-extending drugs and treatments either had poor side-effect profiles, didn’t work in both sexes, or extended life without improving health,” added Cook.
“This does not appear to be the case for IL-11. While these findings are in mice, they raise the tantalizing possibility that the drugs could have a similar effect in elderly humans.”
Anti-IL-11 treatments are currently in human clinical trials for other conditions, potentially providing exciting opportunities to study their effects on aging in humans in the future. The researchers caution that while the results are promising, the safety and effectiveness of these treatments in humans need further validation in clinical trials before anti-IL-11 drugs can be considered for this purpose.
