Juan Carlos Izpisua Belmonte Believes Aging May Come Down to a Cell’s Identity Crisis

It’s in the embryo that the 20,000 or so genes in the human genome start organizing to mature into the more than 200 different cell types in the body—similar to the way young people start discovering their talents and deciding on a career. In other words, like teens, cells develop an identity. 

Over time, however, this cellular identity gets challenged—by molecular processes, inflammation, environmental exposures including pollutants, and behaviors like a lack of physical activity, poor diet, and smoking. The cumulative effects of these assaults, Izpisua Belmonte and other developmental experts believe, drive a significant portion of aging and disease. Restoring this lost cellular identity could help cells to function as they did when they were younger, Izpisua Belmonte believes.

This concept opens up clever ways to confront the deterioration of cells, tissues, and organs. Izpisua Belmonte has found, for example, that as people age, their cells drift toward a certain state that leads to stiffer tissues and greater production of inflammatory factors that can stress and age cells—and that there might be a way to forestall it.

Izpisua Belmonte founded Altos to test his idea. Rather than reprogramming adult cells all the way back to an embryonic state, which is what Shinya Yamanaka demonstrated, Izpisua Belmonte wondered whether, to address disease, partial reprogramming might be sufficient to help cells get back on their proper developmental path and regain their youthful function and identity.

In 2025, Izpisua Belmonte reported that it was indeed possible—both in human cells reprogrammed in the lab, and in mice. Treating the mice with the Yamanaka genetic factors partially reprogrammed and rejuvenated cells in a variety of older animals’ organs, including the kidneys, liver, and intestines; skin cells, for example, regained their ability to regenerate and heal wounds more efficiently.

“If we can tackle the problem of cell identity, we could not just focus on aging itself but on many, many diseases as well,” he says. “Rather than study diseases one by one, we can attack the problem in a more comprehensive way.” The next test is transplantation. Scientists at Altos are starting to determine whether partial reprogramming can help to rejuvenate and redirect aging cells in multiple organs back to a more youthful and functional state, by transplanting them into older animals and monitoring their function. 

For people, he says, the first studies could focus on finding more organs for transplant. It’s well known that younger organs lead to better outcomes for the recipient than older ones; while at Salk, Izpisua Belmonte’s team showed that reprogramming kidneys from older animals helped those kidneys perform as well as kidneys from younger animal donors, and extended the life of the mouse recipient. 

“It’s proof that independently of disease, or of the problem, re-establishing cell identity could have a major effect in the progression of any disease,” he says. So far, in mice, he and his team have found similar success in reprogramming diseased cells in nearly three dozen different conditions.

He cautions, however, that “a mouse is not a human,” and that partial reprogramming as a tool for slowing aging still requires more study. But he believes that if the transplant results are replicated in people, more organs from older donors could be used to save lives—and it would be an important step in moving the field of cellular rejuvenation forward.

The hope is that cellularly, “we are able to mimic what happens during the early years of our lives,” he says. “Whether this could somehow prevent the inevitability of aging is still a major question.” But thanks to his work, it’s a question that can now be asked—and, eventually, answered.