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SINGAPORE — An ageing population will pose major health, social and economic challenges over the coming decades. As people live longer, every year that can be saved by preventing physical decline and frailty and adding another year to life expectancy is estimated to be worth $38 trillion.
A team of scientists at the Duke-NUS Medical School in Singapore thinks they may have found something that can help.
In a new paper published in Nature, the team demonstrates in preclinical studies in mice that the protein interleukin-11 (IL11) actively promotes aging, and that anti-IL11 therapy not only counteracts the deleterious effects of aging but also extends lifespan.
Research has found that the expression levels of IL11 protein in organs increase with age. IL11 is a signaling molecule involved in blood cell formation, preventing fat accumulation, and part of fertility. When these organs produce more IL11, it promotes fat accumulation in the liver and abdomen, and reduces muscle mass and strength, two conditions that are hallmarks of human aging.
“This project began in 2017 when our collaborator sent us tissue samples for another project,” says Anissa Wijaya, assistant professor in the Duke-NUS Cardiovascular and Metabolic Disease Programme. “Out of curiosity, we ran some experiments to look at IL11 levels. We were very excited to see that our measurements clearly showed that IL11 levels increased with age.”
The research team has previously investigated the role of IL11 in the heart and kidney ( Nature),liver( Gastroenterology) and lung ( Science Translational Medicine) has led to the development of experimental anti-IL11 therapies.
Anti-IL11 therapy counteracts the effects of aging
After establishing the role IL11 plays in aging, the team demonstrated that applying this anti-IL11 therapy in the same preclinical model improved metabolism: Mice shifted from producing white fat to producing beneficial brown fat, which breaks down blood sugar and fat molecules to help maintain body temperature and burn calories.
Researchers observed improved muscle function, improved overall health, and up to a 5 percent increase in lifespan for both men and women in the study.
Unlike other drugs known to inhibit specific pathways involved in aging, such as metformin and rapamycin, anti-IL11 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-IL11 therapy reduced the rate of telomere shortening and maintained mitochondrial health and energy-producing capacity.
“Our goal is that one day anti-IL11 therapy will be used as widely as possible, enabling people around the world to live longer, healthier lives,” said Stuart Cook, Tanoto Foundation Professor of Cardiovascular Medicine at Singapore Health Duke-NUS Academic Medical Centre. “But this will not be easy, as approval pathways for drugs to treat ageing are not clearly defined and it is very difficult to raise funding to conduct clinical trials in this area.”
Dr Cook is also a Senior Consultant in the Department of Cardiology at the National Heart Centre Singapore.
“Despite significant increases in life expectancy over recent decades, there remains a large gap between the number of years lived and the number of years lived healthy and free of disease,” said Thomas Coffman, dean of Duke-National University of Singapore. “For a rapidly ageing society like Singapore, this discovery could be transformative, enabling older adults to extend their healthy years, reduce frailty and fall risk, and improve cardiometabolic health.”
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.
