For the first time, scientists have demonstrated how a specific protein increases in organs with age and actively promotes aging — blocking this activity could not only extend lifespan but also slow the physical decline that is currently an inevitable part of aging.
Researchers at Duke-NUS Medical School in Singapore have previously conducted three separate studies looking at interleukin-11 (IL-11) protein expression and its role in heart, kidney, liver and lung health, the last of which has led to an experimental anti-IL-11 therapy in clinical trials aimed at treating fibrotic lung disease.
Building on this work, the team identified a role for IL-11 in the ageing process. Increased production of IL-11 leads to fat accumulation in the liver and abdomen, and loss of muscle mass and strength. Blocking the expression of this protein could significantly reduce these hallmarks of ageing.
“The project began in 2017 when our collaborator sent us tissue samples for another project,” explains lead author Anissa Wijaya, an assistant professor at Duke-NUS. “Out of curiosity, we ran some experiments to look at IL-11 levels. We were very excited to see that our measurements clearly showed that IL-11 levels increased with age.”
The researchers found that deleting this protein protected against age-related decline, frailty and disease in preclinical mouse models. IL-11 The mouse gene extended the animals’ lifespan by an average of 24.9%. When mice were treated with the anti-IL-11 treatment until they died at 75 weeks of age (equivalent to about 55 years in humans), the average lifespan of male mice increased by 22.5% and female mice by 25%.
Not only did the mice live longer, they were also protected from key signs of aging: anti-IL-11 therapy boosted metabolism, caused the animals to produce calorie-burning brown fat rather than problematic white fat deposits, prevented the loss of muscle mass and strength, and protected against multiple diseases and cardiometabolic disorders.
“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 Duke-NUS Dean Professor Thomas Coffman. “This discovery is potentially transformative, enabling older people to extend healthy ageing, reduce the risk of frailty and falls, and improve their cardiometabolic health.”
Cancer is the leading cause of death in aging mice, and the autopsies in this study showed that blocking IL-11 expression significantly reduced the disease. (Clinical trials of anti-IL-11 drugs combined with immunotherapy for cancer are ongoing.)
The treatment also had an effect on overall cellular health, slowing the rate of telomere shortening that occurs with each cell division and maintaining efficient functioning of mitochondria, the powerhouses of cells.Anti-IL-11 therapy is already in early-stage trials in fibrotic lung diseases, and researchers are pleased with its safety profile.
“Our goal is that one day anti-IL-11 therapy will be used as widely as possible, helping people around the world live longer, healthier lives,” said Stuart Cook, professor of cardiovascular medicine at Singapore Health Duke-NUS Academic Medical Centre and senior author of the paper. “But this won’t 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.”
But as scientists continue to search for the holy grail of anti-aging, this may be one of the most promising treatments yet: slowing the aging process and adding a year to life expectancy is estimated to be worth $38 trillion.
The study was published in the journal Nature.
Source: Duke-NUS Medical School
