- Scientists have found that inactivating a protein called IL-11 extends the healthy lifespan of mice by about 25%, and that a similar effect may be possible in humans.
- The researchers found that ablating the IL-11 gene or using anti-IL-11 antibodies dramatically improved the lifespan and health of old mice.
- These findings suggest that anti-IL-11 therapy could combat age-related diseases with minimal side effects, and point to a promising path for future human clinical trials.
The scientific community has long been interested in understanding and extending human lifespan.
According to a new study published in 2011,
The results were striking: mice treated with the anti-IL-11 drug from 75 weeks of age until death had an average lifespan extended by 22.5% in males and 25% in females, surviving for 155 weeks compared with 120 weeks for untreated mice.
Moreover, the treatment significantly reduced cancer-related mortality in the animals, as well as a range of diseases associated with fibrosis, chronic inflammation and poor metabolism that are characteristic of aging.
Importantly, minimal side effects were observed.
Lifespan refers to the total number of years a person lives from birth to death.
Healthy life expectancy, on the other hand, refers to the period of time during an individual’s life in which they remain healthy and free from serious chronic diseases and disabilities.
The main difference between the two is that lifespan focuses on the quantity of life, whereas healthspan focuses on the quality of life during those years.
Co-corresponding author Professor Stuart Cook from the UK Medical Research Council Laboratory of Medical Sciences (MRC LMS), Imperial College London and Duke-NUS Medical School in Singapore explained the key findings of the new study: Today’s Medical News.
“We have demonstrated that suppressing inflammation by inhibiting the interleukin-11 (IL11) gene extends healthspan (healthy living) and lifespan (survival time) in mice. We have repeatedly demonstrated that the effects of IL11 in mouse and human cells are in a 1:1 relationship, indicating that anti-IL11 has the potential to extend healthspan and lifespan in humans. Anti-IL11 is already in human safety testing, so it may be tested in clinical trials in the near future.”
— Professor Stuart Cook
Previously proposed life-extending drugs and treatments have often come with adverse side effects, only worked on one gender, or only extended life without improving health, but IL-11 does not appear to have these limitations.
Although these findings are currently limited to mice, they raise the intriguing possibility that similar effects might be seen in older people.
For example, the treated mice had less cancer, did not show typical signs of aging and frailty, experienced less muscle wasting, and had improved muscle strength — essentially, the older mice that received anti-IL-11 were healthier.
Anti-IL-11 therapeutics are already in clinical trials for other diseases, offering exciting opportunities to study their effects on ageing in the future.
The researchers have been studying IL-11 for many years and first reported it in 2018.
Scientists have previously suggested that IL-11 is a vestige of human evolution.
It is essential for limb regeneration in some animals but is thought to be largely dispensable in humans.
However, after the age of 55, IL-11 production increases and is associated with chronic inflammation.
If an individual experiences two or more of these symptoms, it is
IL-11 gene activity increases with age in all tissues in mice, and when activated, it causes multiple diseases that manifest as age-related diseases and generalized functional decline, affecting vision, hearing, muscle strength, hair, heart function, and kidneys.
“Overall, the data looks robust. The data shows improvements in frailty,” said Ilaria Bellantuono, professor of musculoskeletal ageing at the University of Sheffield, who was not involved in the study.
However, Professor Bellantuano advises caution in making claims of multimorbidity based on these findings.
Bellantuono explained that the mice did not naturally develop chronic disease, but rather experienced impaired function of several organs.
For example, unless mice are genetically modified, they do not naturally develop arteriosclerosis, a major risk factor for heart attack and stroke, and the same is true for diseases such as Alzheimer’s and Parkinson’s.
“If they wanted to claim to prevent multimorbidity, they should have tested their intervention in at least two or three different chronic disease models,” Bellantuono said.
Leading health organisations, including the NHS and WHO, have recognised multimorbidity and frailty as a major global health challenge of the 21st century.
Currently, there is no cure for multiple disorders other than treating each underlying cause separately.
The scientists involved in the study emphasized that these findings are in mice, and that the safety and efficacy of anti-IL-11 treatment in humans must be established through clinical trials before it can be considered for use for this purpose.
Dr Richard Siow FRSB, FESPM, Director of Ageing Research, King’s College, ARK)“These findings provide further insight into the role of suppressing the pro-inflammatory protein IL-11 in reducing cancer mortality in mice and reducing the development of diseases caused by fibrosis, inflammation and poor metabolism that are hallmarks of ageing,” said researchers from King’s College London, who were not involved in the study.
“Studies like this in laboratory mice under well-controlled conditions should be viewed with some caution, especially when inhibiting a single protein appears to slow the aging process. Further research is needed to see whether similar effects on mice are seen in the wild.”
— Dr. Richard Siow
“Furthermore, it’s possible that the protein is required for certain functions in the wild, but that’s not clear in lab mice,” Siow added.
“However, this study does provide us with insight into the role of IL-11 in the aging process that should be considered by the general public throughout their lives, not just older adults and those with age-related diseases,” he said.
“The problem with all these interventions is that there is no evidence for patients,” Bellantuano said.
“Clinical trials are underway in the U.S., but there are scientific hurdles to overcome before these interventions can be offered to patients, including understanding who is at risk of frailty and who would benefit from them,” he said.
Bellantuano added that it would be unrealistic to treat everyone in their 50s for the rest of their lives.
“All medicines have side effects and costs. As a society, we need to improve how we test medicines in patients at risk of frailty, who are often excluded from clinical trials because of their age. Furthermore, our regulatory system does not classify frailty as a medical condition, which impedes drug reimbursement and discourages investment from the pharmaceutical industry.”
— Professor Ilaria Bellantuono
In addition to the practical challenges cited by Bellantuano, more research is needed.
However, although the study was conducted in mice, studies of human cells and tissues have confirmed similar effects, leading the researchers to believe these findings are highly relevant to human health.
They say their work is an important step towards a better understanding of ageing, demonstrating a potential treatment in mice that could extend healthy ageing by reducing frailty and the physiological signs of ageing.
In conclusion, Cook said, “If anti-IL11 could extend human healthspan, it would have a huge impact on the health and wealth of the nation. Adding just one year of lifespan would be worth more than $1 trillion in the United States.”
“It may be possible to extend your lifespan, but again, this is only possible if your health is good,” he added.
