Has this scientist finally found the fountain of youth?

“He went backwards in time,” Izpisúa Belmonte says. All the methylation marks, those epigenetic switches, “are erased,” he adds. “Then you’re starting life again.” Even skin cells from centenarians, scientists have found, can be rewound to a primitive, youthful state. The artificially reprogrammed cells are called induced pluripotent stem cells, or IPSCs. Like the stem cells in embryos, they can then turn into any kind of body cell—skin, bone, muscle, and so on—if given the right chemical signals.

To many scientists, Yamanaka’s discovery was promising mainly as a way to manufacture replacement tissue for use in new types of transplant treatments. In Japan, researchers began an effort to reprogram cells from a Japanese woman in her 80s with a blinding disease, macular degeneration. They were able to take a sample of her cells, return them to an embryonic state with Yamanaka’s factors, and then direct them to become retinal cells. In 2014, the woman became the first person to receive a transplant of such lab-made tissue. It didn’t make her vision sharper, but she did report it as being “brighter,” and it stopped deteriorating.

Before then, though, researchers at the Spanish National Cancer Research Centre had already taken the technology in a new direction when they studied mice whose genomes harbored extra copies of the Yamanaka factors. Turning these on, they demonstrated that cell reprogramming could actually occur inside an adult animal body, not only in a laboratory dish.

The experiment suggested an entirely new form of medicine. You could potentially rejuvenate a person’s entire body. But it also underscored the dangers. Clear away too many of the methylation marks and other footprints of the epigenome and “your cells basically lose their identity,” says Pradeep Reddy, a staff researcher at Salk who worked on these experiments with Izpisúa Belmonte. “You are erasing their memory.” These cellular blank slates can grow into a mature, functioning cell, or into one that never develops the ability to perform its designated task. It can also become a cancer cell.

That’s why the mice I saw in Izpisúa Belmonte’s lab were prone to sprouting tumors. It proved that cellular reprogramming had indeed occurred inside their bodies, but the results were usually fatal.

Izpisúa Belmonte believed there might be a way to give mice a less lethal dose of reprogramming. He was inspired by salamanders, which can regrow an arm or tail. Researchers have yet to determine exactly how amphibians do this, but one theory is that it happens through a process of epigenetic resetting similar to what the Yamanaka factors achieve, though more limited in scope. With salamanders, their cells “just go back a little bit” in time, Izpisúa Belmonte says.

Could the same thing be done to an entire animal? Could it be rejuvenated just enough?

In 2016, the team devised a way to partially rewind the cells in mice with progeria. They genetically modified the mice to produce the Yamanaka factors in their bodies, just as the Spanish researchers had done; but this time, the mice would produce those factors only when given an antibiotic, doxycycline.