 "Could this revolutionise human ageing? – Firstpost")
Recent studies have revealed that blocking a specific protein in middle-aged mice can significantly extend their lifespan and improve overall health. The findings, published in Nature on July 17, have sparked discussions about the potential implications for human ageing.
IL-11, a protein known for promoting inflammation, has been identified as a crucial factor in ageing. Researchers discovered that blocking IL-11 in middle-aged mice not only boosted their metabolism but also reduced frailty and increased lifespan by about 25 per cent. This protein, along with other interleukins, plays a significant role in the immune system and exists in both mice and humans.
Professor Stuart Cook, from the Medical Research Council Laboratory of Medical Science (MRC LMS), Imperial College London, and Duke-NUS Medical School in Singapore, explains, “The IL-11 gene activity increases in all tissues in the mouse with age. When it gets turned on, it causes multimorbidity, which is diseases of ageing and loss of function across the whole body, ranging from eyesight to hearing, from muscle to hair, and from the pump function of the heart to the kidneys.”
How was the study conducted?
The link between IL-11 and ageing was discovered accidentally when molecular biologist Anissa Widjaja, also at Duke-NUS Medical School, detected higher levels of IL-11 in older rats compared to younger ones. This finding led the team to investigate further, revealing that IL-11 levels were consistently higher in older mouse tissues, including skeletal muscle, fat, and liver tissue.
When the researchers deleted the gene coding for IL-11 in some mice, these mice not only had improved healthspans but also lived 25 per cent longer than their counterparts. Similarly, when 75-week-old mice (equivalent to 55 human years) were treated with an anti-IL-11 antibody for 25 weeks, they exhibited reduced frailty, fewer cancers, and overall better health.
What were the results?
The results were dramatic. Treated mice had their median lifespan extended by 22.4 per cent in males and 25 per cent in females, living an average of 155 weeks compared to 120 weeks in untreated mice.
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The treatment also reduced deaths from cancer and other age-related diseases such as fibrosis, chronic inflammation, and poor metabolism. “The treated mice had fewer cancers, and were free from the usual signs of ageing and frailty, but we also saw reduced muscle wasting and improvement in muscle strength,” said Cook.
What about humans?
Although the research has so far been limited to mice, the existence of IL-11 and its molecular partners in humans suggests potential applications. Drug candidates that block IL-11 are already in human trials for conditions like cancer and fibrosis. These treatments might also impact human longevity, though separate clinical trials are needed to confirm this.
Cook highlights the importance of further studies: “There’s a real opportunity here to translate this into clinical therapies. Ageing is a tough field, but there are a lot of therapeutic angles, and a lot more biology left to understand.”
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Determining the effect of anti-IL-11 drug candidates on human longevity poses significant challenges. A clinical trial focused on lifespan would be lengthy and costly, with numerous confounding factors. Instead, researchers might focus on specific age-related conditions like muscle mass loss to obtain quicker and more specific outcomes.
Nature quoted Dan Winer from the Buck Institute for Research on Aging who suggests, “One important next step would be to test candidate IL-11 drugs in mice with diverse genetic backgrounds and in multiple laboratories to be sure that the results are reproducible.”
Are there other drugs in the anti-ageing field?
The magnitude of the response seen with IL-11 blockade is comparable to that observed with rapamycin, another prominent drug in the anti-ageing field. However, rapamycin has been linked to unwanted side effects. Cook notes, “Rapamycin is good for lifespan, but not healthspan.”
Other potential anti-ageing treatments include the diabetes drug metformin and severe calorie restriction, both of which have shown promising results. However, Cook argues that a drug like anti-IL-11 might be more practical and acceptable for people than lifelong calorie restriction.
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Multimorbidity and frailty are among the biggest global healthcare challenges of the 21st century. Conditions associated with ageing, such as lung disease, cardiovascular disease, diabetes, and more, often occur simultaneously in older individuals.
Current treatments target these conditions separately, but a successful anti-IL-11 therapy could address multiple age-related diseases simultaneously, providing a more comprehensive solution.
