An antibody against IL-11 extended mouse lifespan by 22,5–25%; the Nature paper counted tumours in mice that had died, while a viral post claimed “half as many cancer deaths”

An antibody against IL-11 extended mouse lifespan by 22,5–25%; the Nature paper counted tumours in mice that had died, while a viral post claimed “half as many cancer deaths”

On 26 October, entrepreneur Ryan Bethencourt wrote on X that an antibody against IL-11 had extended mouse lifespan and halved cancer deaths, and that three such antibodies were being tested in humans; the post received about 239 thousand views. IL-11 is a protein whose levels rise with age and which promotes inflammation and scarring. On 27 October, researcher Avi Roy responded with a thread checking the post against the Nature paper and the clinical trial registry.

In a Nature paper published on 17 July 2024, Stuart Cook’s group showed that mice lacking the IL-11 gene lived 24,9% longer on average. The gene was disabled from birth, so developmental differences could have affected lifespan. To address this, the researchers gave other mice an antibody that blocks IL-11 once a month from 75 weeks of age (equivalent to 55 years in humans, according to the authors) until death. Median lifespan, the age to which half the group survived, was 117,1 weeks in control females and 146,4 weeks in females given the antibody (25% longer). In males, the corresponding figures were 130,3 and 159,6 weeks (22,5% longer).

The paper’s cancer findings came from necropsies: visible tumours were found in 22 of 36 control mice that had died and in 3 of 19 mice given the antibody. The authors cite evidence that 50–70% of mice die of cancer and interpret the necropsy findings as supporting a reduction in age-related cancers. A press release from the authors’ laboratory says the treatment “substantially reduced deaths from cancer in the animals”; the post says those deaths were halved.

Roy points out that the paper counts tumours present at death, whereas the proportion of deaths caused by cancer is a different measure. According to the list of mice in the supplementary material, by 20 May 2024, 36 of 38 control mice and 19 of 37 mice in the antibody group had died. Tumours were therefore counted in almost the entire control group, but only in the antibody-treated mice that had died by that date. The count excluded 18 surviving mice, all older than any control mouse had been at death. In their response to reviewers, the authors described the early necropsy data as “preliminary and presented for descriptive purposes only”.

Mice given the antibody lost fat, and males ate more. The authors did not establish the cause of the weight loss. They suggest that blocking IL-11 restores “browning” in the white fat of old mice, a process in which the fat becomes heat-producing tissue. Roy observes that a sceptic might see fat loss as a possible reason for the longer lifespan.

The three antibodies that the post’s author says “could extend human lifespan” are being tested for specific diseases: pharmaceutical company Boehringer Ingelheim is testing BI 765423 in 81 patients with pulmonary fibrosis (lung scarring); Lassen Therapeutics tested LASN01, an antibody against the IL-11 receptor, in 41 patients with thyroid eye disease; and Mabwell Bioscience is recruiting 30 patients with pathological skin scars for a trial of 9MW3811. Roy writes: “None of these trials measures ageing or lifespan”.

Boehringer Ingelheim describes BI 765423 as a drug acquired from Enleofen Bio. According to GEN, in January 2020 Enleofen transferred rights to its IL-11 antibodies to Boehringer Ingelheim for diseases involving tissue scarring, primarily in the liver and lungs. Cook and another author of the paper are co-founders and shareholders of Enleofen. The authors also thank Enleofen and Boehringer Ingelheim for permission to use the antibody in the experiment.

Roy considers the BI 765423 lung disease trial the most important: “Before discussing healthy older people, I would like to see months of safe dosing in patients”.