Inhibiting IL-11 increases lifespan in mice by 25%

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As people live longer, preventing the physical decline and frailty that accompany ageing becomes a challenge, and effective interventions are expected to yield important social and economic benefits. Estimates show that slowdown aging Adding just one year of life expectancy is worth $38 trillion. Now, a discovery published in Naturemay have found the key to slowing down aging.

This is the work of a group of scientists from Duke-NUS Medical School from Singapore, who demonstrated in preclinical models that interleukin-11 protein (IL11) actively promotes aging, and administering anti-IL11 therapy not only counteracts the harmful effects of aging, but also extends lifespan. Their discovery could play an important role in countries’ efforts to help their populations live longer and healthier lives.

“This project started in 2017 when one of our employees sent us fabric samples for another project.”

IL11 causes fat accumulation and loss of muscle masstwo key characteristics of aging. In preclinical studies, the team found that IL11 protein levels increase in organs with age, which in turn contributes to the accumulation of fat in the liver and abdomen and a decrease in muscle mass and strength — two conditions that characterize human aging. The team says these findings are the first to demonstrate that IL11 is a key driver of aging.

First and co-correspondent, associate professor Anissa Widjaja from the Duke-NUS Cardiovascular and Metabolic Disorders Programme comments: “This project started in 2017 when a coworker sent us tissue samples for another project. Out of curiosity, I did some experiments to check the IL11 levels. From the readings, we clearly saw that the IL11 levels increased with age, and that’s when we got really excited.”

“We clearly saw from the readings that IL11 levels increased with age, and that’s when we were really excited.”

Having established the role of IL-11 in aging, the team showed that when anti-IL-11 therapy was administered to the same preclinical model, metabolism improved, shifting from the formation of white fat to the formation of healthy brown fat. Brown fat breaks down sugar and fat molecules in the blood, helping to maintain body temperature and burn calories. The researchers also observed improved muscle function and overall health in their study, as well as an increase in life expectancy up to 25% in both sexes.

Unlike other drugs known to inhibit specific pathways involved in aging, such as metformin and rapamycin, anti-IL11 therapy blocks several important signaling mechanisms that become dysfunctional with age, providing protection against multimorbidity caused by cardiometabolic diseases, age-related loss of muscle mass and strength, but also frailty. In addition to these externally observable changes, anti-IL11 therapy also reduced the rate of telomere shortening and preserved mitochondrial health and their ability to generate energy.

Lead Author, Stuart CookTanoto Foundation Professor of Cardiovascular Medicine at SingHealth Duke-NUS Academic Medical Centre and a member of the Duke-NUS Cardiovascular and Metabolic Disorders Programme, explains: “Our goal is that one day anti-IL-11 therapy will be used as widely as possible so that people around the world can live healthier and longer lives. However, this is not easy, as the approval pathways for anti-aging drugs are not clearly defined and raising funds for clinical trials in this area is very difficult.”