Identical twin mice of the same age. The mouse on the left is aging normally without any intervention. The mouse on the right is receiving anti-IL-11 antibody treatment from 55 weeks, which corresponds to middle age in mice, the study found. MRC Institute for Medical Research, UK
A recent study found that inhibiting a specific protein in middle-aged mice significantly extended their lifespan and improved their overall health. Nature The study, published July 17, has sparked debate about its potential implications for human aging.
IL-11, a protein known to promote inflammation, has been identified as a key factor in aging. Researchers found that inhibiting IL-11 in middle-aged mice not only boosted metabolism but also reduced frailty and extended lifespan by about 25 percent. The protein, which plays a key role in the immune system along with other interleukins, is present in both mice and humans.
“IL-11 gene activity increases in all tissues with age in mice,” explains Professor Stuart Cook, from the Medical Research Council Institute of Medical Sciences (MRC LMS), Imperial College London and Duke-NUS Medical School in Singapore. “When activated, this gene causes multimorbidity – a condition that is associated with ageing and loss of function throughout the body, from vision to hearing, muscle to hair, and the pumping function of the heart to the kidneys.”
How was this study conducted?
The link between IL-11 and ageing was discovered by chance when molecular biologist Anissa Wijaya of Duke-NUS Medical School discovered that older rats had higher IL-11 levels than younger rats. This led the team to investigate further and found that IL-11 levels were consistently higher in tissues, including skeletal muscle, fat and liver tissue, in older mice.
When researchers deleted the gene that codes for IL-11 in some mice, these mice not only had a longer healthy lifespan, but also lived 25% longer than controls. Similarly, treating 75-week-old mice (equivalent to 55 human years) with anti-IL-11 antibodies for 25 weeks reduced frailty, reduced cancer, and improved overall health.
What was the outcome?
The results were dramatic: The average lifespan of treated mice increased by 22.4% in males and 25% in females, living 155 weeks longer than the 120 weeks of untreated mice.
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The treatment also reduced deaths from age-related diseases such as cancer, fibrosis, chronic inflammation and poor metabolism. “Not only did the treated mice have less cancer and showed fewer common signs of aging and frailty, they also showed less muscle wasting and improved strength,” Cook said.
What about humans?
Although studies to date have been limited to mice, the presence of IL-11 and its molecular partners in humans suggests potential applications. Candidate drugs that block IL-11 are already being tested in humans for conditions such as cancer and fibrosis. These treatments may also have an impact on human lifespan, but separate clinical trials are needed to confirm this.
Cook emphasizes the importance of further research: “There is a real opportunity here to translate this into clinical treatment. Ageing is a difficult field, but there are many therapeutic perspectives and many biological challenges still to be understood.”
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Determining the impact of anti-IL-11 drug candidates on human lifespan is a major challenge. Clinical trials focused on lifespan would be time-consuming and expensive, with many confounding factors. Instead, researchers might focus on specific age-related symptoms, such as muscle mass loss, to get more rapid and specific results.
Nature “One of the key next steps will be to test candidate IL-11 drugs in mice with diverse genetic backgrounds across multiple laboratories to ensure that results are reproducible,” said Dan Weiner of the Buck Institute on Aging.
Are there any other drugs in the anti-aging field?
The magnitude of responses seen with IL-11 inhibitors is comparable to that seen with rapamycin, another popular drug in the anti-aging field. However, rapamycin is associated with unwanted side effects. Cook points out that “rapamycin is good for longevity, but not good for healthspan.”
Other potential anti-ageing treatments include the diabetes drug metformin and severe calorie restriction, both of which have shown promising results, but Cook argues that a drug like anti-IL-11 may be more practical and acceptable to people than lifelong calorie restriction.
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Multimorbidity and frailty are among the world’s greatest healthcare challenges of the 21st century. Conditions associated with aging, such as pulmonary disease, cardiovascular disease, and diabetes, often occur together in older adults.
Current therapies treat these conditions individually, but successful anti-IL-11 therapy could potentially address multiple age-related diseases simultaneously, providing a more comprehensive solution.
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