Studies have found that blocking an immune protein called IL-11 extends the lifespan of laboratory mice.Credit: Panther Media GmbH/Alamy
A protein that promotes inflammation may be the key to living a longer, healthier life: Blocking a protein called IL-11 boosted metabolism, reduced frailty and extended lifespan by about 25% in middle-aged mice.
Although the team only tested these health effects in mice, IL-11 and its molecular partners (including interleukins, chemical messengers of the immune system) are present in humans, and drug candidates that block IL-11 are already in clinical trials for cancer and fibrosis, a condition in which scar tissue replaces healthy tissue as we age.
The new results, released on July 17th, Nature1suggest that these potential treatments may also have an impact on lifespan, but separate clinical trials are needed to be sure.
Still, the clear path for IL-11 to be tested in humans sets it apart from a host of other proteins and anti-aging interventions that have shown promise in animal models but have stalled midway through clinical trials. “There’s a real opportunity here to translate this into clinical treatment,” says Cathy Slack, who studies the biology of aging at the University of Warwick in the UK. “And that’s where the field is currently stuck.”
Accidental discovery
Researchers have known for some time that chronic inflammation contributes to diseases associated with aging. As the body ages and damaged proteins and other molecules build up, the immune system often sees this as a sign of infection, says Stuart Cook, a medical researcher who studies IL-11 at Duke-National University of Singapore’s School of Medicine. This can trigger an inflammatory response that can cause further damage and contribute to diseases like cancer and autoimmune disorders.
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The pro-inflammatory role of IL-11 has also long been evident.2But the protein’s link to aging was discovered by chance when Cook’s colleague, molecular biologist Anissa Wijaya, also of the Duke University and National University of Singapore School of Medicine, was testing a method to detect IL-11. She happened to include protein samples from old rats and found that their IL-11 levels were much higher than those from young rats.
The results pointed the research team, which had not previously focused on longevity, in a new direction: They examined a variety of samples from young and old mice and found that IL-11 was consistently more abundant in tissues from older mice, including skeletal muscle, fat, and liver tissue.1Deleting the gene that codes for the IL-11 protein in some mice increased the mice’s health span, helping them stay healthy longer and live 25% longer than mice with normal IL-11 levels.
Next steps
The team got similar results when they used an antibody against IL-11 to block the protein for 25 weeks in 75-week-old mice (equivalent to 55 human years). Similar antibodies are being tested in human clinical trials for cancer and fibrosis.
The magnitude of the response is similar to that seen in mice treated with rapamycin, a hot drug being tested in the anti-aging field. But rapamycin comes with unwanted side effects, says Cook, who is co-founder of Singapore-based Enreofen Ltd, which is developing drugs to treat fibrosis. “Rapamycin is good for longevity, but it’s not good for healthspan,” he says.
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The results are striking and should spur further research, says Dan Weiner, who studies the immune system’s role in aging at the Buck Institute for Aging in Novato, Calif. One important next step will be to test candidate IL-11 drugs in mice with diverse genetic backgrounds and across multiple labs to make sure the results are reproducible, he says.
Furthermore, it may be difficult to determine the effect of potential anti-IL-11 drugs on human lifespan: clinical trials investigating the effect on lifespan would be long and expensive, and results may be difficult to interpret because of the many confounding factors that affect lifespan.
Cook said researchers might instead see quicker results and more tangible outcomes by focusing on specific conditions associated with aging, such as muscle mass loss.
“Aging is a difficult field,” he adds, “but there are many therapeutic perspectives and a lot of the biology still to be understood.”
