Study Shows Blocking IL-11 Protein Extends Mouse Lifespan by 25%Study Shows Blocking IL-11 Protein Extends Mouse Lifespan by 25% Researchers from the Medical Research Council Laboratory of Medical Science and Imperial College London have made a significant discovery that could have implications for human aging. They found that “switching off” a protein called IL-11 significantly extended the healthy lifespan of mice by almost 25%. Experiment and Findings * Mice were engineered with a deleted gene for IL-11, resulting in a lifespan increase of over 20%. * 75-week-old mice (about 55 years in human age) were treated with an anti-IL-11 antibody. * Median lifespan was extended by 22.4% in males and 25% in females, with an average life expectancy of 155 weeks compared to 120 weeks in untreated mice. Mechanism and Benefits * IL-11 has been shown to promote inflammation, fibrosis, and muscle loss in the body. * Blocking IL-11 reduced cancer mortality and diseases associated with aging such as fibrosis, chronic inflammation, and poor metabolism. * Treated mice exhibited improved muscle strength and reduced signs of frailty. Significance * The study challenges previous notions that life-extending treatments come with side effects or are ineffective in both sexes. * IL-11 inhibition appears to promote healthy aging without significant adverse effects. * Anti-IL-11 treatments are currently undergoing clinical trials for other conditions, offering potential opportunities for studying their effects in older humans. Conclusion The research underscores the potential of targeting IL-11 signaling to extend healthy aging. While further studies are needed to establish safety and effectiveness in humans, the findings raise exciting possibilities for combating the challenges of multimorbidity and frailty associated with aging.
Scientists from the Medical Research Council Laboratory of Medical Science and Imperial College London have discovered that ‘switching off’ a protein called IL-11 can significantly extend the healthy lifespan of mice by almost 25%.
The scientists, who worked with colleagues at Duke-NUS Medical School in Singapore, tested the effects of IL-11 by creating mice from which the gene that produces IL-11 (interleukin 11) had been deleted. This extended the lifespan of the mice by more than 20% on average.
They also treated 75-week-old mice – equivalent to about 55 years of age in humans – with an injection of an anti-IL-11 antibody, a drug that stops the effects of IL-11 in the body.
The results, published in Naturewere dramatic, with mice given the anti-IL-11 drug from 75 weeks until death extending their median lifespan by 22.4% in males and 25% in females. The mice lived an average of 155 weeks, compared to 120 weeks in untreated mice.
The treatment largely reduced cancer mortality in the animals, and also reduced many diseases caused by fibrosis, chronic inflammation and poor metabolism that are characteristic of aging. Very few side effects were observed.
Professor Stuart Cook, co-corresponding author, from the Medical Research Council Laboratory of Medical Science (MRC LMS), Imperial College London and Duke-NUS Medical School in Singapore, said: “These findings are very exciting. The treated mice had fewer cancers and were free of the usual signs of ageing and frailty, but we also saw less muscle loss and improvements in muscle strength. In other words, the old mice given anti-IL11 were healthier.”
“Previously proposed life-extending drugs and treatments either had few side effects, were ineffective in both sexes, or could extend life but not healthy life. However, this does not appear to be the case for IL-11.”
“Although these findings were only made in mice, it raises the tantalizing possibility that the drugs could have a similar effect in older people. Anti-IL-11 treatments are currently in human clinical trials for other conditions, which may provide interesting opportunities to study their effects in older people in the future.”
The researchers have been studying IL-11 for years and in 2018 were the first to demonstrate that IL-11 is a profibrotic and pro-inflammatory protein. In doing so, they put an end to years of incorrect characterization as antifibrotic and anti-inflammatory.
Assistant Professor Anissa Widjaja, who was co-corresponding author, from Duke-NUS Medical School, Singapore, said: “This project started in 2017 when one of our collaborators sent us some tissue samples for another project. Out of curiosity, I did some experiments to check the IL-11 levels. From the measurements, we could clearly see that the levels of IL-11 increased with age and that’s when we got really excited!”
“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. Although our work was done in mice, we hope that these findings will be highly relevant to human health, as we have seen similar effects in studies of human cells and tissues.
“This research is an important step towards a better understanding of aging. We have demonstrated in mice a therapy that could potentially extend healthy aging by reducing vulnerability and the physiological manifestations of aging.”
Scientists have previously suggested that IL-11 is a holdover from human evolution, as it is vital for limb regeneration in some species, but is thought to be largely redundant in humans.
However, after about age 55, people produce more IL-11, and previous research has linked this to chronic inflammation, fibrosis in organs, metabolic disorders, muscle wasting (sarcopenia), frailty, and cardiac fibrosis. These conditions are many of the signs we associate with aging.
When one person has two or more of these conditions, it is called multimorbidity. This includes lung disease, cardiovascular disease, diabetes, deterioration of vision and hearing, and many more conditions.
Professor Cook said: “IL-11 gene activity increases in all tissues of the mouse with age. When activated, it causes multimorbidity, which are diseases associated with ageing and loss of function throughout the body, ranging from vision to hearing, from muscles to hair, and from the pumping function of the heart to the kidneys.”
According to many leading health organisations, including the NHS and WHO, multimorbidity and frailty are among the greatest global healthcare challenges of the 21st century.*
There is currently no treatment available for multimorbidity other than attempting to treat the various underlying causes individually.
The scientists caution that the results of this study were conducted in mice and that the safety and effectiveness of these treatments in humans should be further established in clinical trials before people consider using anti-IL-11 drugs for this purpose.
The research was primarily funded by the National Medical Research Council (Singapore) and the Medical Research Council (UK).
Source:
Research and innovation in the United Kingdom
Journal reference:
Widjaja, A. A., Lim, W.-W., Viswanathan, S., Chothani, S., Corden, B., Dasan, C. M., Goh, J. W. T., Lim, R., Singh, B. K., Tan, J., Pua, C. J., Lim, S. Y., Adami, E., Schafer, S., George, B. L., Sweeney, M., Xie, C., Tripathi, M., Sims, N. A., & Hübner, N. (2024). Inhibition of IL-11 signaling extends healthspan and lifespan in mammals. Nature, 1–9. https://doi.org/10.1038/s41586-024-07701-9
