Turning off a single protein extends mice’s lifespan by 25%

Recent research has uncovered a groundbreaking approach to extending the lifespan of mammals by inhibiting a pro-inflammatory protein called IL-11. This study, conducted by a team of scientists from the UK and Singapore, showed the approach can not only improve overall longevity but also mitigate age-related diseases.

Cytokines and age

During the COVID-19 pandemic, the term “cytokine storm” entered the public lexicon. It described a severe immune reaction observed in some patients infected with the SARS-CoV-2 virus. Cytokines are small proteins secreted by cells, particularly those in the immune system, that act as signaling molecules to regulate immunity, inflammation, and blood cell production. They play crucial roles in a number of physiological processes.

Increasingly, researchers are also looking at some cytokines as a potential way of dealing with aging.

Specifically, interleukin-11 (IL-11), is a cytokine that plays a significant role in processes including inflammation, fibrosis, and and cellular healing. Recent research suggests that inhibiting IL-11 signaling can improve health and lifespan by inhibiting inflammation and age-related diseases.

In the new study, researchers tested the effects of IL-11 on health and lifespan in mice. The team, led by Anissa A. Widjaja and Stuart A. Cook, included researchers from the Medical Research Council Laboratory of Medical Science (MRC LMS), Imperial College London and Duke-NUS Medical School in Singapore. They conducted two experiments.

In the first experiment, they deleted the gene that produces IL-11 in mice. This extended the lifespan of the mice by 20% on average. In the second experiment, they treated 75-week-old mice (the rough equivalent of 55 years in humans) with an anti-IL-11 antibody. This extended the lifespan even more — by over 22% for males and over 24% for females.

The good news continued. The mice who were given the treatment were also healthier and had more muscle mass.

“These findings are very exciting,” says Professor Stuart Cook, co-corresponding author on the study. 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.”

Could this be done in humans?

Humans also have IL-11. Initially, it was thought to be an evolutionary relic for us. For some animals, it’s vital for limb regeneration, but since we don’t have that ability, it was considered useless. However, recent research showed that after the age of 55, production of IL-11 increases substantially.

The IL-11 cytokine was also found to be linked to various health problems, including inflammation and metabolic decline. So, it’s reasonable to suspect that inhibiting it could also be beneficial to us.

Anti-IL-11 therapies are already being tested for other diseases, so this study provides a new potential use for these treatments. If successful in humans, this could lead to new ways to treat or prevent age-related conditions, helping people stay healthier for longer as they age.

“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,” says Cook.

“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 ageing humans in the future.”

Treating aging as a disease

This research opens the door to developing therapies that specifically target the aging process, offering hope for a future where aging doesn’t necessarily mean a decline in health and well-being.

Typically, aging comes with multiple health problems, and our best current approach is to take them one by one and deal with them. Aging has been viewed as an inevitable, natural process rather than a condition that can be treated or managed. However, the discovery that inhibiting IL-11 can extend both the health span and lifespan in mice suggests that it might be possible to slow down or even reverse some of the detrimental effects of aging.

The implications of this research are profound.

If similar results can be replicated in humans (which is a big ‘if’), it could revolutionize the way we approach aging. Rather than merely treating individual age-related diseases as they arise, we could develop therapies aimed at the underlying mechanisms of aging itself. This would not only improve the quality of life for older adults but also reduce the overall burden on healthcare systems by preventing multiple chronic conditions.

Essentially, the study paves the way for a new field of medicine focused on the proactive management of aging, transforming it from an unavoidable decline into a manageable and treatable condition. If we can confirm it on humans, that is.

Journal Reference: Anissa A. Widjaja et al. Inhibition of IL-11 signalling extends mammalian healthspan and lifespan. Nature, 2024; DOI: 10.1038/s41586-024-07701-9