For the first time, scientists have demonstrated how a specific protein increases in our organs as we get older and actively promotes the aging process. By blocking this activity, it could not only help us live longer, but slow the physical decline that is, right now, an inevitable part of aging.
Researchers at Duke-NUS Medical School in Singapore have previously undertaken three different studies to examine interleukin-11 (IL-11) protein expression and its role in heart and kidney, liver and lung health. The lattermost research has led to an experimental anti-IL-11 therapy that’s currently in clinical trials to treat fibrotic lung disease.
Building on this work, the team identified IL-11’s role in the aging process, with its increased production leading to fat accumulating in the liver and abdomen, as well as reduced muscle mass and strength. By blocking this protein expression, these hallmarks of aging could be drastically reduced.
“This project started back in 2017 when a collaborator of ours sent us some tissue samples for another project,” explained first author Anissa Widjaja, an assistant professor at Duke-NUS. “Out of curiosity, I ran some experiments to check for IL-11 levels. From the readings, we could clearly see that the levels of IL-11 increased with age and that’s when we got really excited.”
In a preclinical mouse model, the researchers found that deleting this protein provided protection against age-related decline, frailty and disease. Deleting the IL-11 gene in mice extended the lives of the animals by an average of 24.9%. When mice were given an anti-IL-11 therapeutic at 75 weeks of age (the equivalent of around 55 human years) until death, the average lifespan of male mice was increased by 22.5% and 25% in female mice.
The mice didn’t just live longer, they were shielded from key signs of aging. Anti-IL-11 therapy boosted metabolism, with the animals producing calorie-burning brown fat, not problematic stores of white fat, blocked the loss of muscle mass and strength, and protected against multimorbidity and cardiometabolic diseases.
“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 Professor Thomas Coffman, Dean of Duke-NUS. “This discovery could be transformative, enabling older adults to prolong healthy aging, reducing frailty and risk of falls while improving cardiometabolic health.”
Cancer is a leading cause of death in old mice, and autopsies in this study showed that inhibiting IL-11 expression significantly reduced this disease. (Clinical trials of an anti-IL 11 drug in combination with immunotherapy for cancer is in the pipeline.)
The therapy also benefited cell health across the board, reducing the rate of telomere shortening – which occurs every time a cell divides – and keeping the powerhouse mitochondria functioning efficiently. With an anti-IL-11 therapy already in the early phases of testing for fibrotic lung disease, the researchers have been pleased with its safety profile.
“Our aim is that one day, anti-IL-11 therapy will be used as widely as possible, so that people the world over can lead healthier lives for longer,” said senior author Stuart Cook, Professor of Cardiovascular Medicine at the SingHealth Duke-NUS Academic Medical Center. “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.”
However, this may be one of the most promising treatments yet, as scientists continue their search for anti-aging’s holy grail. It’s estimated that slowing down the aging process in a way that increases life expectancy by a single year would be valued at US$38 trillion.
The study was published in the journal Nature.
Source: Duke-NUS Medical School
