Scientists from the Medical Research Council’s Institute of Medical Sciences and Imperial College London have found that ‘switching off’ a protein called IL-11 can significantly extend the healthy lifespan of mice by around 25%.
The scientists, working with colleagues at Duke-NUS Medical School in Singapore, tested the effects of IL-11 (interleukin 11) in mice lacking the gene that produces it, which extended the mice’s lifespan by an average of more than 20%.
The researchers also treated 75-week-old mice (equivalent to about 55 human years) with injections of an anti-IL-11 antibody, a drug that blocks the action of IL-11 in the body.
Increased life expectancy
Result is, NatureThe results were dramatic: the average lifespan of mice treated with the anti-IL-11 drug from 75 weeks of age until death was increased by 22.4% in males and 25% in females, to 155 weeks, compared with 120 weeks for untreated mice.
The treatment significantly reduced cancer mortality in the animals, as well as mitigating many of the diseases caused by fibrosis, chronic inflammation, and metabolic decline that are hallmarks of ageing, with minimal observed side effects.
Fewer cancers and fewer signs of aging and frailty
Co-corresponding author Professor Stuart Cook, from the UK Medical Research Council Laboratory of Medical Sciences (MRC LMS), Imperial College London and Duke-NUS School of Medicine in Singapore, said:
“These findings are very exciting. Not only did the treated mice have less cancer and showed no typical signs of ageing and frailty, but they also showed less muscle wasting and improved muscle strength. In other words, the old mice that received anti-IL11 were healthier.”
“The life-prolonging drugs and treatments proposed so far have had adverse side effects, been ineffective in both men and women, or have been effective in extending life but not in extending healthy lifespan, but this does not seem to be the case with IL-11.”
“Although these findings were only made in mice, they raise the intriguing possibility that this drug might have a similar effect in older people. Anti-IL-11 treatments are currently in clinical trials for other diseases, which could provide exciting opportunities to study their effects in older people in the future.”
Researchers have been studying IL-11 for many years, and in 2018 First to demonstrate that IL-11 is a profibrotic and proinflammatory proteinIt overturns its long-standing mischaracterization as anti-fibrotic and anti-inflammatory.
IL-11 levels increase with age
“This study is a first-of-its-kind opportunity for researchers to advance the understanding of how cancer treatment can be used in the treatment of cancer,” said co-corresponding author Anissa Wijaya, Associate Professor at the Duke-NUS Medical School in Singapore.
“The 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!”
“We found that these elevated levels contribute to adverse effects in the body, such as inflammation and the inhibition of organ healing and regeneration after injury. Although our study was conducted in mice, we have seen similar effects in studies of human cells and tissues, so we are hopeful that these findings will be highly relevant to human health.”
“This study is an important step towards a deeper understanding of aging, and we have demonstrated in mice a treatment that has the potential to extend healthy aging by reducing frailty and the physiological signs of aging.”
Previously, scientists had hypothesized that IL-11 was an evolutionary vestige in humans because it is essential for limb regeneration in some animal species but is thought to be largely dispensable in humans.
IL-11 is associated with chronic inflammation and frailty
However, in humans, IL-11 production increases after age 55, and previous studies have shown that this is associated with chronic inflammation, organ fibrosis, metabolic disorders, muscle wasting (sarcopenia), frailty, and cardiac fibrosis – many of the symptoms associated with aging.
When an individual has two or more such conditions, it is known as multimorbidity and encompasses a range of conditions including lung disease, cardiovascular disease, diabetes, vision and hearing loss, and many more.
Professor Cook said:
“In mice, IL-11 gene activity increases with age in all tissues. When this gene is activated, it causes a multimorbidity disorder that is associated with aging and loss of function throughout the body, from vision to hearing, muscle to hair, and the pumping function of the heart to the kidneys.”
Multimorbidity is one of the world’s biggest medical challenges
Multimorbidity and frailty are recognised as one of the world’s greatest health challenges of the 21st century, and many major health agencies, such as the US Department of Health, National Health ServiceWHO.*
Currently, there is no cure for multimorbidity other than treating the multiple underlying causes individually.
