Switching Off Inflammatory Protein Leads to Longer, Healthier Lifespans in Mice

Breakthrough Discovery at Medical Research Council Laboratory

S ave far-reaching implications for human health and longevity. Their research has revealed that turning off a protein known as IL-11 can significantly extend the healthy lifespan of mice by nearly 25%. IL-11, a cytokine involved in various cellular processes, was previously linked to inflammation and tissue repair. However, this new study demonstrates that suppressing IL-11 activity not only delays the onset of age-related diseases but also enhances overall health during the aging process. This finding opens up exciting possibilities for developing therapies that target IL-11, potentially revolutionizing the way we approach aging and age-related conditions in humans.

The implications of this discovery are profound, as it challenges existing paradigms in aging research and offers a new avenue for extending healthy life expectancy. By reducing IL-11 levels, the researchers were able to slow down the biological processes that typically lead to the deterioration of bodily functions in older mice. This resulted in the animals maintaining better physical and cognitive function well into old age, suggesting that similar approaches could one day be applied to humans. If these findings can be replicated in human studies, they could pave the way for treatments that not only extend lifespan but also improve the quality of life in later years, offering hope for a healthier aging population.

The Experiment: Gene Deletion and Antibody Treatment

Creating IL-11 Deficient Mice

Working alongside colleagues at Duke-NUS Medical School in Singapore, researchers have made a significant breakthrough in the field of aging and longevity. By genetically engineering mice to lack the gene responsible for producing IL-11 (interleukin 11), the team observed a remarkable extension in the animals’ average lifespan. The absence of IL-11 led to a more than 20% increase in the lifespan of these mice, marking a significant step forward in understanding the role this protein plays in aging. IL-11 is a cytokine involved in inflammation and various cellular processes, and its suppression appears to delay the onset of age-related diseases, thereby promoting healthier aging.

This discovery not only provides new insights into the molecular mechanisms of aging but also holds potential for the development of innovative therapies aimed at extending healthy human lifespans. The success of this genetic modification in mice suggests that targeting IL-11 could be a promising strategy for combating the effects of aging and enhancing the quality of life in older adults. Future research will focus on translating these findings to human studies, with the hope of developing treatments that can slow down the aging process, reduce the incidence of age-related diseases, and ultimately extend the years of healthy living.

Anti-IL-11 Antibody Treatment

In addition to genetic modification, the team treated 75-week-old mice—equivalent to around 55 human years—with injections of an anti-IL-11 antibody, a drug designed to inhibit the effects of IL-11 in the body. The results, published in Nature, were remarkable: mice treated with the anti-IL-11 drug from 75 weeks of age until death had their median lifespan extended by 22.4% in males and 25% in females, living an average of 155 weeks compared to 120 weeks in untreated mice.

Significant Health Benefits Observed

Reduction in Cancer and Chronic Diseases

The treatment notably reduced deaths from cancer and lowered the incidence of diseases caused by fibrosis, chronic inflammation, and poor metabolism, all of which are hallmarks of aging. Remarkably, very few side effects were observed.

Improvements in Muscle Health

Professor Stuart Cook, co-corresponding author from the Medical Research Council Laboratory of Medical Science, Imperial College London, and Duke-NUS Medical School in Singapore, highlighted the health improvements in treated mice. “The treated mice had fewer cancers and were free from the usual signs of aging and frailty. We also saw reduced muscle wasting and improvements in muscle strength. In other words, the old mice receiving anti-IL11 were healthier.”

Potential for Human Application

Promising Results in Mice

While these findings are currently limited to mice, they raise the tantalizing possibility that similar effects could be achieved in elderly humans. Anti-IL-11 treatments are already undergoing clinical trials for other conditions, potentially providing exciting opportunities to study their effects on aging in humans in the future.

The Science Behind IL-11

Revising the Role of IL-11

Researchers have been investigating IL-11 for many years. In 2018, they were the first to demonstrate that IL-11 is a pro-fibrotic and pro-inflammatory protein, overturning the long-held belief that it was anti-fibrotic and anti-inflammatory.

Discovery of IL-11’s Negative Effects

Assistant Professor Anissa Widjaja, co-corresponding author from Duke-NUS Medical School, Singapore, shared the origins of this project. “This project started back in 2017 when a collaborator sent us tissue samples for another project. Out of curiosity, I ran some experiments to check for IL-11 levels. We saw that IL-11 levels increased with age, which got us excited!”

Understanding the Impact of IL-11 on Aging

Link to Chronic Conditions

Research revealed that rising IL-11 levels contribute to negative effects such as inflammation and hindered organ healing and regeneration. Although the study was conducted in mice, similar effects have been observed in human cells and tissues, suggesting relevance to human health.

Evolutionary Perspective

IL-11 is considered an evolutionary relic in humans, essential for limb regeneration in some species but largely redundant in humans. After about age 55, humans produce more IL-11, which has been linked to chronic inflammation, organ fibrosis, metabolic disorders, muscle wasting (sarcopenia), frailty, and cardiac fibrosis. These conditions are often associated with aging.

Addressing Multimorbidity and Frailty

The Scope of Multimorbidity

When multiple chronic conditions occur in an individual, it is known as multimorbidity. This encompasses a range of issues, including lung disease, cardiovascular disease, diabetes, vision and hearing decline, among others. Multimorbidity and frailty are recognized as some of the most significant global healthcare challenges of the 21st century by leading health bodies, including the NHS and WHO.

The Need for Comprehensive Treatment

Currently, there is no treatment for multimorbidity other than addressing each underlying cause individually. The study’s authors caution that while the results are promising, further clinical trials are necessary to establish the safety and effectiveness of anti-IL-11 treatments in humans.

Funding and Future Directions

Support and Collaboration

The study was primarily funded by the National Medical Research Council (Singapore) and the Medical Research Council (UK). This research marks an important step toward better understanding aging and demonstrates a potential therapy to extend healthy aging by reducing frailty and the physiological manifestations of aging.

Looking Forward

As anti-IL-11 treatments progress through clinical trials, there is hope that this groundbreaking research will lead to new therapies for extending healthy human lifespans, offering a promising future for aging populations worldwide.