Mice on the right display graying and hair loss – Credit: MRC Laboratory of Medical Science / Duke-NUS Medical School

Scientists have discovered that ‘switching off’ a protein called IL-11 can significantly increase the healthy lifespan of mice by almost 25%.

The UK researchers at Medical Research Council Laboratory and Imperial College London, worked with colleagues at Duke-NUS Medical School in Singapore to test the effects on mice that had the interleukin 11 gene deleted, which extended the lives of the mice by over 20% on average.

They treated 75-week-old mice—equivalent to the age of about 55 years in humans—with an injection of an anti-IL-11 antibody, a drug that stops the effects of the IL-11 in the body.

The results were dramatic, with mice given the anti-IL-11 drug from 75 weeks of age until death having their median lifespan extended by 22.4% in males and 25% in females. The mice lived for an average of 155 weeks, compared with 120 weeks in untreated mice.

The treatment largely reduced deaths from cancer in the animals, as well as reducing the many diseases caused by fibrosis, chronic inflammation and poor metabolism, which are hallmarks of aging. There were very few side effects observed.

“These findings are very exciting,” said Professor Stuart Cook, a co-author of the July paper published in Nature.

“The treated mice had fewer cancers, and were free from the usual signs of aging and frailty, and we also saw reduced muscle wasting and improvement in muscle strength.”

“While these findings are only in mice, it raises the tantalizing possibility that the drugs could have a similar effect in elderly humans. Anti-IL-11 treatments are currently in human clinical trials for other conditions, potentially providing exciting opportunities to study its effects in aging humans in the future.”

After investigating IL-11 for many years, the researchers in 2018 they were the first to show that IL-11 is a pro-fibrotic and pro-inflammatory protein, overturning years of incorrect characterization as anti-fibrotic and anti-inflammatory.

Assistant Professor Anissa Widjaja, who was co-corresponding author, explained how the project began back in 2017. “A collaborator of ours sent us some tissue samples for another project. 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!”

“We found these rising levels contribute to negative effects in the body, such as inflammation and preventing organs from healing and regenerating after injury. Although our work was done in mice, we hope that these findings will be highly relevant to human health, given that we have seen similar effects in studies of human cells and tissues.

Previously, scientists have wondered whether IL-11 was an evolutionary hangover in humans, because while it is vital for limb regeneration in some animal species, it is thought to be largely redundant in humans.

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However, after around age 55 in humans, more IL-11 is produced and past research has linked this to chronic inflammation, fibrosis in organs, disorders of metabolism, muscle wasting (sarcopenia), frailty, and cardiac fibrosis—all signs associated with aging.

When two or more such conditions occur in an individual, it is known as multi-morbidity, which encompasses a range of conditions including lung disease, cardiovascular disease, diabetes, vision and hearing decline, and a host of other conditions.

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“The IL-11 gene activity increases in all tissues in the mouse with age,” continues Professor Cook, “causing loss of function across the whole body, ranging from eyesight to hearing, from muscle to hair, and from the pump function of the heart to the kidneys.”

Currently, no treatment for multi-morbidity is available, other than to try to treat the separate underlying causes individually.

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The effectiveness of these treatments in human clinical trials will determine whether doctors consider using anti-IL-11 drugs for this purpose.

The study was primarily funded by the National Medical Research Council (Singapore), and the Medical Research Council (UK).

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