July 17, 2024

expert reaction to study on the ageing effects of a pro-inflammatory protein, IL11, in mice

A study published in Nature looks at the inflammatory protein IL-11 and ageing in mice. 

Prof Ilaria Bellantuono, Professor of Musculoskeletal Ageing, University of Sheffield, said:

“Overall, the data seems solid. The data show an improvement in frailty. I would be cautious about claiming an improvement in multimorbidity. Mice do not develop chronic diseases spontaneously. They develop decreased function in some organs. For example, mice do not develop atherosclerosis (building up of plaques in the vessels due to high cholesterol), which is the main risk factor for heart attacks and strokes. To do that, animals need to be genetically modified so that they can accumulate high level of cholesterol in the blood and form plaques.  Similarly for other diseases such as Alzheimer’s or Parkinson’s Disease. The intervention described here delays the loss of organ function with age. If they wanted to claim to prevent multimorbidity they should have tested the intervention in at least 2-3 models of chronic diseases.”

How does this work fit with the existing evidence?

“This is another potential therapy targeting a mechanism of ageing, which may benefit frailty. I don’t see this as being any better than other interventions published previously (e.g. senolytics). Potentially this intervention is less cost effective. Antibody-based therapies are usually more expensive than small molecules. In addition, there is no evidence that it would work in advanced age when deficits are more prominent. The intervention in this study started at 18 months of age. In mice, this is equivalent to a 50-year-old person without severe signs of ageing.

What are the implications in the real world?  Is there any overspeculation?

“The problem with all these interventions is that we do not have evidence in patients. Although trials are underway in the USA, there are scientific hurdles to overcome to use these interventions in patients, such as understanding who is at risk of frailty and would benefit from the intervention. It is unthinkable to treat every 50 years old for the rest of their life. Every drug has side effects and there is a cost associated with it. We also need to develop knowledge on how to test medicinal drugs in patients at risk of frailty, who are often excluded from clinical trials due to their age. Finally, the regulatory system, which approves the use of medicinal drugs, does not recognise frailty as a condition, which means the costs of drugs cannot be reimbursed. This stops investments from the pharmaceutical industry.”

‘Inhibition of IL-11 signalling extends mammalian healthspan and lifespan’ by Stuart A. Cook et al. was published in Nature at 16:00 UK time on Wednesday 17 July 2024.

DOI: 10.1038/s41586-024-07701-9

Declared interests

Prof Ilaria Bellantuono: Co-Director of the Healthy Lifespan Institute, I lead UKAgeNet and I receive funding from the Dunhill Medical Trust and Michael J Fox Foundation for research.