An Elixir of Youth: Supermodel Mice and a New Drug Candidate to Slow Aging

Scientists have identified a drug candidate that extends laboratory animals’ lives by approximately 25%. There is hope this discovery could also slow human aging.

The study’s lead author, Professor Stuart Cook, says, “Taking the drug we developed to live longer is easier than calorie restriction. Would you want a half-starved, thoroughly unpleasant life from age 40 just to live five more years at the end? I would not.”

The treated mice were called “supermodel grannies” in the laboratory because they looked youthful. They were healthier and stronger and developed less cancer than untreated mice.

The drug is also being tested in humans, but whether it will have the same antiaging effects is unknown.

The Historical Search for an Elixir of Youth

The search for longevity is one of humanity’s oldest and most enduring concerns. Scientists, however, have long known that the aging process can actually be modified. This has been recognized for some time.

Research in laboratory animals, for example, has demonstrated that eating less makes them live longer.

Aging research now involves many investigators exploring its molecular processes and trying to manipulate them.

The team at the MRC Laboratory of Medical Sciences, Imperial College London, and Duke-NUS Medical School was studying interleukin-11, a protein whose levels increase as people age, raising inflammation and triggering biological switches that control the rate of aging.

Longer, Healthier Lives

The researchers performed two experiments:

1. They genetically engineered mice not to produce interleukin-11.
2. When mice reached 75 weeks (roughly equivalent to a 55-year-old human), they regularly administered an experimental drug to clear this protein from the body.

The results, published on 17 July 2024 in Nature, showed lifespan increases of 20-25%, depending on the experiment and the mice’s sex. Older laboratory mice usually die of cancer, but those lacking interleukin-11 developed much less of it. Muscle function also improved; they were leaner, had healthier fur, and performed better on frailty measures.

According to the paper, the drug is an anti-IL-11 antibody inhibiting IL-11 (interleukin-11) signaling. Its code name is X203. X203 was used to investigate the effects of inhibiting IL-11 signaling pathways on aging and age-related conditions. Another antibody neutralizing the IL11RA receptor was identified as X209. These antibodies were used to block IL-11’s biological effects in the experiments.

Researcher Professor Stuart Cook said, “I try not to get too excited, because is this too good to be true?! There is so much fake stuff out there, so I try to stick to the data, and these are among the strongest data,” he said.

Professor Cook said he “absolutely” believed the approach was worth testing in human aging, that it could be “transformative” if effective, and that he would consider taking the drug himself.

What About Humans?

The major unanswered questions are whether the same effects can be achieved in humans and whether adverse effects will be tolerable. Interleukin-11 plays a role in early human development. Very rarely, people are born without producing it, affecting how skull bones fuse, joints, and tooth eruption. It also plays a role in scarring.

The researchers believe interleukin-11 plays a harmful, aging-promoting role later in life. The experimental antibody drug targeting this protein is being tested in patients with pulmonary fibrosis, in which lung scarring makes breathing difficult.

Professor Cook said trials were incomplete, but the data suggested the drug was safe. This is the latest approach to “treating” aging with drugs. Metformin, a type-2 diabetes drug, and rapamycin, used to prevent transplant rejection, are actively being investigated for antiaging properties.

In the video below, Stuart Cook explains how they developed the idea of targeting interleukin-11:

“Interleukin 11, or IL-11 for short, is a gene that produces a protein in our bodies. This protein activates fibroblasts and immune cells. It is an evolutionary feature inherited from fish, in which it serves beneficial functions. For us, however, it is an evolutionary remnant causing harmful effects and disease. IL-11 causes inflammation and fibrosis and prevents proper tissue regeneration. In 2016-2017, we discovered that the gene had been mischaracterized and were the first to identify it as a profibrotic, proinflammatory factor in the heart and kidneys. We later found the same effects in many tissues, forming the basis of our aging research.

While studying fibrosis (tissue scarring), we noticed elevated IL-11 protein in older animals. We investigated aging in mice and found expression rising with age across all tissues. This showed that activation causes problems and is associated with multimorbidity, where aging brings multiple diseases throughout the body. These range from vision and hearing loss and hair loss to muscle loss and impaired heart and kidney function.

In mice, genetically switching off this gene substantially improved aging-related diseases. We then moved to antibody treatment, a more translationally relevant approach. Specially developed binding antibodies attach to IL-11 molecules and inactivate them. We treated mice equivalent to 55-year-old humans and observed stronger muscles, better lungs, healthier skin, and improved hearing and vision. We showed that a drug given later in life could provide the same benefits as deleting the gene from birth, suggesting potential for human treatment.

Our group studies the cellular processes underlying aging and related diseases such as cancer. This treatment positively affected many aging markers; understanding how these mechanisms interrelate could help us design better therapies. A key finding is that one treatment — an anti-IL-11 antibody — can improve both healthspan and lifespan. Although its target audience is the entire world population, human trials must come first, and funding and regulatory challenges must be resolved. Genetic and animal studies nevertheless suggest a promising safety profile.”

Other Researchers’ Views

Professor Anissa Widjaja of Duke-NUS Medical School said, “Although our study was in mice, we hope these findings will be highly important for human health, since we saw similar effects in human cell and tissue studies,” she said. “This is an important step in understanding aging, and we demonstrated a treatment in mice that could potentially extend healthy aging.”

Ilaria Bellantuono, professor of musculoskeletal aging at the University of Sheffield, said, “Overall, the data look sound. This is another potential treatment targeting aging mechanisms and could benefit frailty,” she said. However, she noted the lack of evidence in patients and concerns such as cost, saying it would be “unthinkable to treat every 50-year-old for the rest of their life”.

Commentary and Caution

Science continues to open new doors in the search for a long, healthy life. Although this candidate has shown exciting results, more research is clearly needed to understand its effects and adverse effects in humans. These mouse studies offer hope for human health, but the treatment is not currently available for routine human use.