A simple monthly injection allows mice to live 25% longer and free from diseases

The strategy — the injection of a simple antibody — has already begun to be tested in humans in an attempt to cure age-related illnesses

In two 105-week-old female mice, the one that received the X203 antibody had less gray hair and is thinner.MRC-LMS / Duke-NUS

It seems too good to be true, but biochemist Jesús Gil speaks enthusiastically from his laboratory in London. “There is no reason to think that what we have seen in mice will not work in people,” he says. What they have observed in rodents is verging on the miraculous: a team of scientists has given monthly injections of a simple antibody to mice that are almost 18 months old, an age equivalent to 55 human years. These animals have lived up to 25% longer than their peers and in good health, with lower incidence of cancer, less cholesterol, and greater muscle strength. It is as if human life expectancy had skyrocketed to 104 years, instead of the current 83 in Spain, for example.

The results are visible to the naked eye, explains cardiologist Stuart Cook, co-director of the research at the MRC Laboratory of Medical Sciences in London. “The mice that received the X203 antibody looked leaner and more active, with better coat color — fewer gray hairs — and better vision, hearing, and walking ability.” Antibodies are proteins that circulate in the blood to defend the body against foreign substances, such as viruses and bacteria. In the case of X203, it is designed to block another natural protein with potent effects on aging: interleukin 11, whose concentration increases with age, causing cells to stop multiplying while accumulating and releasing harmful substances that cause inflammation and damage to nearby cells.

Cook stresses that there are already trials in people of experimental treatments to block interleukin 11, but they are not focused on studying aging over years or decades. He himself has founded a company, Enleofen, which is collaborating with the German pharmaceutical company Boehringer Ingelheim on the first tests of a similar antibody in healthy volunteers. Two other companies, the U.S.-based Lassen and China’s Mabwell, have also initiated similar projects, with the aim of curing pulmonary fibrosis and other age-related diseases.

“We have seen no adverse effects in mice. Increasing longevity and prolonging healthy life is the opposite of an adverse effect,” says Cook. The cardiologist adds that the first results in humans, from the Lassen trials, also show an “excellent safety profile.” In mice, the injection is made directly into the abdominal cavity for 25 weeks until euthanasia, the equivalent of administering it to a person for almost two decades. In humans, the injection is intravenous.

“To date, we have observed full equivalence between what interleukin 11 does in mice and humans. In the case of longevity, mice die mostly from cancer, whereas humans die mostly from cardiovascular disease and cancer. You would expect to see fewer tumors in humans with this therapy, as has already been seen in mice,” Cook explains. “As for heart disease, we’re not so sure, but interleukin 11-blocking treatments improved metabolism and cholesterol levels in mice, so it could also have effects on cardiovascular disease in humans. We will only know if clinical trials designed to study aging are conducted,” cautions the cardiologist, co-lead author of the paper with biologist Anissa Widjaja of the Duke-NUS Medical School at the National University of Singapore.

Biochemist Jesús Gil of the MRC Laboratory of Medical Sciences in London.Jesús Gil

Gil leads his own group at the Laboratory of Medical Sciences, a national center of the UK Medical Research Council. His team studies senescence, the state in which cells stop reproducing but do not die. As they accumulate, they promote inflammation, aging and cancer. “Inhibiting interleukin 11 can inhibit senescence,” says Gil, who has also conducted experiments with human cells. His results were published July 17 in the journal Nature.

Spanish biologist Rafael de Cabo, head of translational gerontology at the U.S. National Institute on Aging, applauds the new work, in which he did not participate. “The magnitude of life extension in mice is quite impressive,” he says. De Cabo, however, is cautious. “The data is super solid, but there are details that could call the interpretation a little into question. For example, they only use one genetic line of mice: the C57BLACK6, which are very common. To carry out longevity studies you have to use several strains of mice, in several places, to avoid it being a one-time observation, as has happened on a thousand occasions,” he warns.

However, the biologist is optimistic. “It is clear that playing with the inhibition of interleukin 11 has beneficial effects on the health of mice. The accumulation of data from this and other studies indicates that it can probably be used for specific types of diseases in humans,” he says. “The problem we have right now in the field of aging research is that everyone wants to live much longer, but no one has the patience needed to do the studies well. We have to perform long studies in humans, because they have not been done.”

The global scientific community is working on several promising strategies to extend healthy life, such as rapamycin and metformin, and even to reverse aging, which is the ambitious goal of Altos Labs, a U.S. company created in 2022 with a huge budget of some $3 billion. For De Cabo, there are still no certainties. “In humans there is still not enough data to predict positive changes in health with any of the interventions we have done. The most solid are calorie restriction and increased physical activity,” he points out: eat less and move more, without the need for injections.

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