Recent research has unveiled a remarkable discovery that could revolutionize our understanding of aging and its associated health challenges. Scientists have found that blocking a specific protein, known as IL-11, in middle-aged mice can dramatically extend their lifespan and enhance their overall well-being. The findings, published in the prestigious journal Nature, have ignited discussions about the potential implications for human aging and the development of novel anti-aging therapies.
IL-11, a protein known for its role in promoting inflammation, has been identified as a crucial factor in the aging process. Researchers from the Medical Research Council Laboratory of Medical Science (MRC LMS) and Duke-NUS Medical School, led by Professor Stuart Cook, discovered that blocking IL-11 in middle-aged mice not only boosted their metabolism but also reduced frailty and significantly increased their lifespan, by as much as 25 percent. This protein, along with other interleukins, plays a critical role in the immune system and is present in both mice and humans. Professor Cook explains that the activity of the IL-11 gene increases in all tissues as mice age. This increase leads to multimorbidity, a condition characterized by multiple age-related diseases and a decline in bodily function across various systems, from vision and hearing to muscle strength, hair growth, and the functionality of vital organs like the heart and kidneys.
The link between IL-11 and aging was initially discovered by molecular biologist Anissa Widjaja, also at Duke-NUS Medical School, who observed higher levels of IL-11 in older rats compared to younger ones. This discovery prompted the team to delve deeper into the role of IL-11 in aging, revealing consistently elevated levels of this protein in older mouse tissues, including skeletal muscle, fat, and liver tissue.
Intriguingly, when researchers genetically deleted the gene responsible for producing IL-11 in some mice, these mice exhibited improved health spans and lived 25 percent longer than their counterparts. Similarly, when 75-week-old mice, equivalent to 55 human years, were treated with an anti-IL-11 antibody for 25 weeks, they displayed reduced frailty, lower cancer rates, and overall better health.
The results of the study were truly remarkable. Treated mice experienced a median lifespan extension of 22.4 percent in males and 25 percent in females, living an average of 155 weeks compared to 120 weeks for untreated mice. Furthermore, the treatment significantly reduced deaths from cancer and other age-related diseases such as fibrosis, chronic inflammation, and impaired metabolism. Professor Cook highlighted the benefits of the treatment, stating that the treated mice not only had fewer cancers but also exhibited fewer signs of aging and frailty, along with reduced muscle wasting and improved muscle strength.
While the research has focused on mice, the existence of IL-11 and its associated molecules in humans raises exciting possibilities for therapeutic interventions. Drug candidates that block IL-11 are already undergoing human trials for conditions like cancer and fibrosis. These treatments could potentially impact human longevity, though separate clinical trials are needed to confirm this. Professor Cook emphasizes the importance of further research, stating that there is a real opportunity to translate these findings into clinical therapies. He acknowledges that aging is a complex field, but highlights the potential for various therapeutic angles and the need for continued biological research.
Determining the effect of anti-IL-11 drug candidates on human lifespan presents significant challenges. A clinical trial focused solely on lifespan would be lengthy, expensive, and subject to numerous confounding factors. Instead, researchers might focus on specific age-related conditions, such as muscle mass loss, to obtain quicker and more focused outcomes. Dan Winer from the Buck Institute for Research on Aging suggests that testing candidate IL-11 drugs in mice with diverse genetic backgrounds and in multiple laboratories is crucial to ensure the reproducibility of the results.
The magnitude of the response seen with IL-11 blockade is comparable to that observed with rapamycin, another prominent drug in the anti-aging field. However, rapamycin has been linked to unwanted side effects. Professor Cook notes that while rapamycin is effective in extending lifespan, it does not necessarily improve healthspan. Other potential anti-aging treatments include the diabetes drug metformin and severe calorie restriction, both of which have shown promising results. However, Professor Cook argues that a drug like anti-IL-11 might be more practical and acceptable for people than lifelong calorie restriction.
Multimorbidity and frailty are major global healthcare challenges of the 21st century. Conditions associated with aging, such as lung disease, cardiovascular disease, diabetes, and more, often occur simultaneously in older individuals. Current treatments address these conditions individually. However, a successful anti-IL-11 therapy could offer a more comprehensive solution by addressing multiple age-related diseases simultaneously, potentially transforming the way we approach aging and its associated health challenges.
