Credit: MRC Laboratory of Medical Science
Scientists at
the Medical Research Council Laboratory of Medical Science and Imperial College
London have discovered that 'switching off' a protein called IL-11 can
significantly increase the healthy lifespan of mice by almost 25%.
The scientists, working with colleagues at Duke-NUS
Medical School in Singapore, tested the effects of IL-11 by creating mice that
had the gene producing IL-11 (interleukin 11) deleted. This extended the lives
of the mice by over 20% on average.
They also 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 which stops the effects of the IL-11 in the body.
The results, published in Nature, 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.
Video of Professor Stuart Cook being interviewed
about the study findings. Credit: MRC Laboratory of Medical Science
Professor Stuart Cook, who was co-corresponding author, from the Medical
Research Council Laboratory of Medical Science (MRC LMS), Imperial College
London and Duke-NUS Medical School in Singapore, said, "These findings are
very exciting. The treated mice had fewer cancers, and were free from the usual
signs of aging and frailty, but we also saw reduced muscle wasting and
improvement in muscle strength. In other words, the old mice receiving
anti-IL11 were healthier."
"Previously proposed life-extending drugs and treatments have either
had poor side-effect profiles, or don't work in both sexes, or could extend
life, but not healthy life, however this does not appear to be the case for
IL-11."
"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."
The researchers have been investigating IL-11 for many years and 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, from
Duke-NUS Medical School, Singapore, said, "This project started back in
2017 when 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.
"This research is an important step toward better understanding aging
and we have demonstrated, in mice, a therapy that could potentially extend
healthy aging, by reducing frailty and the physiological manifestations of
aging."
Video showing the knockout mice that do not
produce IL-11 on the left, and normally aging mice on the right, at 90-95 weeks
old. Credit: MRC Laboratory of Medical Science / Duke-NUS Medical School
Previously, scientists have posited that IL-11 is an evolutionary hangover
in humans, as while it is vital for limb regeneration in some animal species,
it is thought to be largely redundant in humans.
However, after about the age of 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. These conditions are many of the signs we associate with aging.
When two or more such conditions occur in an individual, it is known as
multimorbidity, which encompasses a range of conditions including lung disease, cardiovascular disease, diabetes,
vision and hearing decline and a host of other conditions.
Professor Cook said, "The IL-11 gene activity increases in all tissues
in the mouse with age. When it gets turned on it causes multimorbidity, which
is diseases of aging and 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."
Multimorbidity and frailty are acknowledged to be among the biggest global
health care challenges of the 21st century, according to many leading health
bodies, including the NHS, and
WHO.
Currently, no treatment for multimorbidity is available, other than to try
to treat the separate multiple underlying causes individually.
The scientists caution that the results in this study were in mice and the safety and effectiveness of these treatments in humans needs further establishing in clinical trials before people consider using anti-IL-11 drugs for this purpose.
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