Inhibiting inflammatory protein interleukin-11 led to leaner mice with improved muscle function and better frailty measure scores.
Researchers from the Medical Research Council Laboratory of Medical Science at Imperial College London and Duke-NUS Medical School in Singapore have published compelling evidence in Nature suggesting that targeting the protein interleukin-11 (IL-11) could not only counteract aging but also extend lifespan [1].
This preclinical study, conducted on mice, demonstrated that inhibiting IL-11 leads to remarkable improvements in health metrics and longevity. Mice treated with an anti-IL-11 antibody showed enhanced muscle function, reduced fat accumulation and preserved telomere length and mitochondrial health. The intervention resulted in an extension of lifespan by up to 25% in female mice and 22.4% in male mice, with significant reductions in cancer incidence and other age-related diseases [1].
Understandably, these results caused headlines around the world and a social media furore. Longevity author and commentator Andrew Steele tweeted:
“This is a big result! 25% life extension puts it up there with rapamycin, the top-ranked drug when it comes up extending lifespan in mice.
“Even more exciting, the antibody in question is already in human trials for autoimmune disease, and it looks safe!”
Longevity.Technology: Multimorbidity, the coexistence of two or more (and often multiple) chronic conditions within an individual, presents a huge challenge to global healthcare systems. This phenomenon, the risk of which increases with aging, encompasses a range of health issues, including cardiovascular disease, diabetes and neurodegenerative disorders, among others, and suffering from multimorbidity also increases the risk of developing diseases of aging, fueling a vicious circle of physical and cognitive decline and mortality.
The increasing prevalence of multimorbidity is a substantial burden on healthcare resources; it significantly diminishes quality of life and complicates medical treatment, and effective interventions that can delay the onset or progression of these conditions are desperately needed. The new findings on IL-11 offer a promising avenue for future research and therapeutic development.
The team at Imperial College and Duke-NUS initially began their research into IL-11 while studying its role in various organs.
Anissa Widjaja, an assistant professor in the Duke-NUS Cardiovascular and Metabolic Disorders Programme, explained that the project kicked off when a collaborator sent the team some tissue samples for another project.
“Out of curiosity, I ran some experiments to check for IL11 levels,” she said. “From the readings, we could clearly see that the levels of IL11 increased with age and that’s when we got really excited [2].”
IL-11, a signaling molecule involved in several biological processes, was found to increase with age across various organs. This upregulation of IL-11 was linked to adverse aging markers such as fat accumulation in the liver and abdomen, as well as reduced muscle mass and strength. The team’s previous research had already implicated IL-11 in cardiovascular and metabolic disorders, leading to the development of an experimental anti-IL-11 therapy [3].
Professor Stuart Cook, from the Medical Research Council Laboratory of Medical Science (MRC LMS), Imperial College London and Duke-NUS Medical School in Singapore, who led the study, said: “The IL-11 gene goes up in all tissues in the mouse with age. When it gets turned on it causes multimorbidity, which is diseases of ageing 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 [4].”
Extending lifespan and improving healthspan
The researchers demonstrated that mice which had had the IL-11 gene knocked out lived significantly longer and exhibited better health compared with their counterparts – the mice also demonstrated reduced obesity and fewer hallmarks of multimorbidity.
After demonstrating the effects in the genetic knock-out mice, the researchers administered an anti-IL-11 antibody to normal mice at an age equivalent to mid-life in humans (approximately 55 years old). This antibody neutralizes the effects of naturally occurring IL-11, which increases with age in both mice and humans. Upon treatment, these middle-aged mice exhibited an extended lifespan and, more importantly, an extended healthy lifespan. The treated mice experienced fewer instances of cancer and showed reductions in age-associated conditions such as obesity, fibrosis, and other issues caused by chronic inflammation. These outcomes align with the researchers’ hypothesis that IL-11 is a central mediator of multimorbidity, driving various age-related pathologies. The mice also showed marked improvements in metabolic function, including a shift from white fat to brown fat, which is known for its role in burning calories and maintaining body temperature. As well as higher frailty scores and grip strength, the treated mice exhibited enhanced muscle function and overall health, with a lifespan increase of up to 22.4% in males and 25% in females [1].
The authors suggest that the anti-IL-11 therapy, which is currently in early-stage clinical trials for fibroinflammatory diseases, could be more effective than existing interventions like metformin and rapamycin, as it targets multiple aging pathways simultaneously [1].
In addition, the therapy appeared to preserve telomere length and mitochondrial function, both critical markers of cellular aging. Highlighting the broader implications of these results, Cook said: “Our aim is that one day, anti-IL11 therapy will be used as widely as possible, so that people the world over can lead healthier lives for longer [2].”
While the results from the mouse model are promising, translating these findings to human aging presents several challenges. Anti-IL-11 treatments are currently in clinical trials for specific fibrotic conditions, providing a pathway to investigate their safety and efficacy in humans, and while the potential for anti-IL-11 therapy to address multimorbidity could represent a major breakthrough in aging research, as Cook noted, there are still hurdles to overcome.
“…Approval pathways for drugs to treat aging are not well-defined, and raising funds to do clinical trials in this area is very challenging [2].”
[1] https://www.nature.com/articles/s41586-024-07701-9
[2] https://corporate.dukehealth.org/news/interleukin-linked-muscle-loss-fat-accumulation-aging
[3] https://www.nature.com/articles/nature24676
[4] https://lms.mrc.ac.uk/scientists-find-master-switch-which-could-hold-the-key-to-longer-healthier-lives/
Photograph: LightFieldStudios/Envato
