NEW YORK – The scientific community has long been interested in understanding and extending human life. In a new piece of research, published in Nature,Trusted Source researchers at the Medical Research Council Laboratory of Medical Science and Imperial College London, in collaboration with Duke-NUS Medical School, administered an anti-IL-11 antibody — a drug that inhibits IL-11’s effects — to mice that were 75 weeks old, comparable to about 55 years in humans.
The results were significant: mice treated with the anti-IL-11 drug from 75 weeks of age until their death showed a median lifespan extension of 22.5% in males and 25% in females, living an average of 155 weeks compared to 120 weeks in untreated mice.
In addition, the treatment significantly decreased cancer-related deaths in the animals and also reduced various diseases associated with fibrosis, chronic inflammation, and poor metabolism, which are typical of aging.
Importantly, only minimal side effects were observed.
Lifespan refers to the total number of years an individual lives, from birth to death.
Healthspan, on the other hand, is the period of an individual’s life during which they remain healthy and free from serious chronic diseases or disabilities.
The key difference between the two is that while lifespan focuses on the quantity of life, healthspan emphasizes the quality of life during those years.
Co-corresponding author Professor Stuart Cook, from the Medical Research Council Laboratory of Medical Science (MRC LMS), Imperial College London, and Duke-NUS Medical School in Singapore, explained the key findings of this new study to Medical News Today.
“We showed that inhibiting inflammation by blocking the interleukin 11 (IL11) gene extended the healthspan (healthy living) and lifetime (time lived) in mice. We have repeatedly shown a 1:1 relationship between IL11 effects in mouse and human cells and so this opens the possibility that anti-IL11 might work to extend human healthspan and lifespan, which might be tested in the near future in clinical trials as anti-Il11 is already in safety testing trials in humans.”
— Professor Stuart Cook
Unlike previously proposed life-extending drugs and treatments, which often have poor side-effect profiles, work in only one sex, or extend life without improving health, IL-11 does not seem to have these limitations.
Although these findings are currently limited to mice, they suggest the intriguing possibility that similar effects could be seen in elderly humans.
For example, treated mice exhibited fewer cancers and avoided typical signs of aging and frailty, showing reduced muscle wasting and improved muscle strength. Essentially, the older mice receiving anti-IL-11 were healthier.
Anti-IL-11 treatments are already undergoing human clinical trials for other conditions, offering exciting opportunities to study its effects on aging in the future.
The researchers have been studying IL-11 for many years and, in 2018, were the first to demonstrate that IL-11 is a pro-fibrotic and pro-inflammatory proteinTrusted Source, challenging the long-held belief that it was anti-fibrotic and anti-inflammatory.
Previously, scientists have suggested that IL-11 is an evolutionary hangover in humans.
While essential for limb regeneration in some animals, it is largely considered redundant in humans.
However, after the age of 55, IL-11 production increases in humans and has been linked to chronic inflammation, fibrosis in organsTrusted Source, metabolic disorders, muscle wasting (sarcopenia), frailty, and cardiac fibrosis — many signs of aging.
When an individual experiences two or more of these conditions, it is termed multimorbidityTrusted Source, encompassing a variety of ailments such as lung disease, cardiovascular disease, diabetes, and sensory decline, among others.
IL-11 gene activity increases in all mouse tissues with age, and when activated, it leads to multimorbidity, manifesting as age-related diseases and functional decline throughout the body, affecting vision, hearing, muscle strength, hair, heart function, and kidneys.
Professor Ilaria Bellantuono, professor of musculoskeletal aging at the University of Sheffield, who was not involved in the study, said “Overall, the data seems solid. The data show an improvement in frailty.”
However, Professor Bellantuano advises caution in claiming an improvement in multimorbidity, based on these findings.
Bellantuono explained that mice do not naturally develop chronic diseases but rather show decreased function in some organs,
For example, mice do not naturally develop atherosclerosis, a major risk factor for heart attacks and strokes, unless genetically modified. This also applies to diseases like Alzheimer’s and Parkinson’s.
“If they wanted to claim to prevent multimorbidity they should have tested the intervention in at least 2-3 models of chronic diseases,” Bellantuono pointed out.
Leading health organizations, including the NHS and WHO, recognize multimorbidity and frailty as major global health challenges of the 21st century.
Currently, no treatment exists for multimorbidity beyond addressing each underlying cause separately.
The scientists involved in this research emphasized that these study results were in mice, and the safety and effectiveness of anti-IL-11 treatments in humans must be established through clinical trials before considering their use for this purpose.
Dr. Richard Siow FRSB, FESPM, director, Aging Research at King’s (ARK), King’s College London, who was not involved in the study, said, “These findings provide further insights in the role of repressing the pro-inflammatory protein IL-11 reduced deaths in mice from cancer and reduced the incidence of diseases caused by fibrosis, inflammation, and poor metabolism, which are hallmarks of aging.”
“Such studies in laboratory mice under well-controlled environments should be viewed with some caution especially when suppressing a single protein appears to slow down the aging process. Further research is needed to see whether the same benefits for mice would be seen in the wild.”
— Dr. Richard Siow
“In addition, there might be a requirement of this protein for a specific function in the wild which is not apparent in the lab mice,” Siow added.
This article appeared in Medical News Today
