Interleukin Linked to Muscle Loss, Fat Accumulation of Aging
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SINGAPORE — An aging population will bring colossal health, social, and economic challenges over the coming decades. As people live longer, anything that might stave off physical decline and frailty to increase life expectancy by just one year is estimated to be worth $38 trillion.
A team of scientists from Duke-NUS Medical School in Singapore think they may have found something that could help.
In a new paper appearing in Nature, the team demonstrated in preclinical mouse studies that the protein interleukin-11 (IL11) actively promotes aging, and that giving an anti-IL11 therapy not only counteracts the deleterious effects of aging but also increases lifespan.
Their studies showed that with age, organs expressed increasing levels of the IL11 protein, a signaling molecule involved in the formation of blood cells, preventing fat accumulation, and some aspects of fertility. When more IL11 was produced by these organs, it promoted fat accumulation in the liver and abdomen, and reduced muscle mass and strength — two conditions that are hallmarks of human aging.
“This project started back in 017 when a collaborator of ours sent us some tissue samples for another project,” said Anissa Widjaja, an assistant professor in the Duke-NUS Cardiovascular and Metabolic Disorders Programme. “Out of curiosity, I ran some experiments to check for IL11 levels. From the readings, we could clearly see that the levels of IL11 increased with age and that’s when we got really excited.”
The team’s previous research on IL11’s role in the heart and kidney (published in Nature), liver (published in Gastroenterology) and lung (published in Science Translational Medicine) led to the development of an experimental anti-IL11 therapy.
Anti-IL11 therapy counteracts effects of aging
After establishing IL11’s role in aging, the team demonstrated that by applying this anti-IL11 therapy in the same preclinical model, metabolism was improved. The mice shifted from generating white fat to beneficial brown fat. Brown fat breaks down blood sugar and fat molecules to help maintain body temperature and burn calories.
The researchers also observed improved muscle function and overall better health in their study, as well as an increased lifespan by up to 5 per cent in both sexes.
Unlike other drugs known to inhibit specific pathways involved in aging, such as metformin and rapamycin, anti-IL11 therapy blocks multiple major signaling mechanisms that become dysfunctional with age, offering protection against cardio-metabolic diseases, age-related loss of muscle mass and strength as well as frailty.
In addition to these externally observable changes, anti-IL11 therapy also reduced the rate of telomere shortening and preserved mitochondria’s health and ability to generate energy.
“Our aim is that one day, anti-IL11 therapy will be used as widely as possible, so that people the world over can lead healthier lives for longer,” said Stuart Cook, the Tanoto Foundation Professor of Cardiovascular Medicine at the SingHealth Duke-NUS Academic Medical Centre. “However, this is not easy, as approval pathways for drugs to treat aging are not well-defined, and raising funds to do clinical trials in this area is very challenging.”
Cook is also senior consultant with the Department of Cardiology at the National Heart Centre Singapore.
“Despite average life expectancy increasing markedly over recent decades, there’s a notable disparity between years lived and years of healthy living, free of disease,” said Thomas Coffman, dean of Duke-NUS. “For rapidly aging societies like Singapore’s, this discovery could be transformative, enabling older adults to prolong healthy aging, reducing frailty and risk of falls while improving cardio-metabolic health.
In this latest work, the Duke-NUS team collaborated with scientists from the National Heart Centre Singapore; the MRC Laboratory of Medical Sciences in the UK; the Max Delbruck Centre for Molecular Medicine in Germany; and the University of Melbourne in Australia.