Scientists identify interleukin-11 as key driver of aging

Population aging will pose enormous health, social and economic challenges over the coming decades. As people live longer, halting age-related physical decline and frailty is the ultimate goal, and effective interventions are predicted to bring significant societal and economic benefits. It has been estimated that just one additional year of life expectancy due to a slowdown in population aging could be worth US$38 trillion.

In a discovery published in 2010, NatureA team of scientists from the Duke University and National University of Singapore School of Medicine in Singapore may have discovered the key to slowing down aging.

In preclinical models, the team demonstrated that the protein interleukin-11 (IL-11) actively promotes aging and that anti-IL-11 therapy not only counteracts the deleterious effects of aging but also extends lifespan, a discovery that could play an important role in countries’ efforts to improve health and lead longer lives for their populations.

IL-11 leads to two key hallmarks of aging: fat accumulation and loss of muscle mass.

In preclinical studies, the team found that expression levels of IL-11 protein in organs increased with age, which promoted fat accumulation in the liver and abdomen, and caused a loss of muscle mass and strength – two hallmarks of human aging.

According to the research team, these findings are the first to demonstrate that IL-11 is a key factor in aging.

“This study is a first- and co-corresponding author on the Cardiovascular and Metabolic Disease Programme at Duke-NUS, Associate Professor Anissa Wijaya, said:

“This project started in 2017 when our collaborator sent us tissue samples for another project. Out of curiosity, we performed some experiments to look at IL-11 levels. The measurements clearly showed that IL-11 levels increased with age, which got us very excited.”

Anti-IL-11 therapy counteracts the effects of aging

After establishing the role of IL-11 in aging, the team demonstrated that applying anti-IL-11 therapy in the same preclinical model improved metabolism, shifting it from producing white fat to producing beneficial brown fat, which breaks down blood sugar and fat molecules and helps maintain body temperature and burn calories.

In their study, researchers observed improved muscle function, improved overall health, and up to a 25 percent increase in lifespan for both men and women.

Unlike other drugs known to inhibit specific pathways involved in aging, such as metformin or rapamycin, anti-IL-11 therapy inhibits multiple key signaling mechanisms that become dysfunctional with age, providing protection against cardiometabolic disease, age-related loss of muscle mass and strength, and frailty.

In addition to these externally observable changes, anti-IL-11 therapy reduced the rate of telomere shortening and maintained mitochondrial health and energy-producing capacity.

“Our aim is that anti-IL-11 therapies can one day be used as widely as possible, helping people around the world live longer, healthier lives. But this is not easy – approval pathways for drugs to treat ageing are not clearly defined and it is very difficult to raise the funding to conduct clinical trials in this area,” said Stuart Cook, Tanoto Foundation Professor of Cardiovascular Medicine at Singapore Health Duke-NUS Academic Medical Centre, who is also involved in the Duke-NUS Cardiovascular and Metabolic Disease Programme.

Assessing the potential of the research, Professor Thomas Coffman, Dean of Duke National University of Singapore, said, “Despite significant increases in life expectancy over recent decades, there remains a significant gap between the number of years lived and the number of years lived healthy and disease-free. For a rapidly ageing societies like Singapore, this discovery is potentially transformative, enabling older adults to extend their healthy ageing, reduce the risk of frailty and falls, and improve their cardiometabolic health.”

The research team has previously investigated the role of IL-11 in the heart and kidney ( Nature 2017), Liver (published in 2017) Department of Gastroenterology 2019) and Lungs (published in 2019) Science Translational Medicine This research, published in 2019, led to the development of experimental anti-IL-11 therapies.

For this latest study, the Duke-NUS team collaborated with scientists from the National Heart Centre Singapore, the MRC Institute for Medical Research in the UK, the Max Delbruck Centre for Molecular Medicine in Germany and the University of Melbourne in Australia.