Shinya Yamanaka Made Cells Young Again. Can That Reverse Aging?
Time · LC · trust 52/100
Dr. Shinya Yamanaka can no longer enjoy a beer in peace. After a long day at a recent conference in Montreal, the scientist found a seat at the quiet hotel bar, hoping for a few moments to himself. “But unfortunately, or fortunately, a group of Japanese businessmen came into the bar,” he says. And although scientists don’t get recognized very often, Yamanaka is a celebrity in Japan.
He doesn’t mind. Celebrity, he knows, is a small price to pay for the profound impact that he has on an impressively wide range of scientific fields: developmental biology, regenerative medicine, chronic-disease treatments, and, increasingly, longevity. In 2006, he published a groundbreaking paper that would forever change our understanding about how the human body develops and ages, and how to reverse those processes. In 2012, Yamanaka earned the Nobel Prize in Physiology or Medicine for his work, becoming a hero in his country and inspiring generations of scientists worldwide.
What Yamanaka achieved was long thought to be impossible: turning back the clock of human cells. Certain animals can regenerate cells, tissues, and entire limbs, but human cells seemed to develop only in one irreversible direction. Yamanaka proved that theory wrong, showing first in animals and then in people that any adult cell could become like those found in embryos, capable of developing into any of the body’s different types of cells. This discovery catalyzed new ways of treating disease by replacing failing cells. This year, the first treatments based on his discovery 20 years ago became available to some patients.
“I can’t believe it’s been 20 years already,” Yamanaka said in a recent interview at the Center for iPS Cell Research and Application (CiRA) at Kyoto University, which he helped create and directed for 12 years. (He remains there as professor and director emeritus.) “And I would say, so far, so good. The technology has grown, so now we are seeing medical applications of this on a small scale.”
We may be at just the start of how Yamanaka’s discovery transforms human health. If diseased or injured cells can be replaced, then why not reprogram aging ones to become youthful and vigorous again? It is one of the most actively researched areas in the longevity field. Scientists are finding that it may not even be necessary to reprogram older cells all the way back to an embryonic, blank-slate state; even partially reprogramming them could rejuvenate cells enough to slow some aging processes. The hope is that one day, aging itself may be “treatable” with fresh sets of cells and tissues that work like decades-younger versions of themselves. “It’s a very active area [of research],” Yamanaka says. “And I think partial reprogramming is a very powerful potential way to live healthier and longer.”
Yamanaka didn’t start his career as a scientist but as a physician. Born in Osaka, where his father made saw parts, he liked to take apart clocks and radios, although he wasn’t always successful in putting them back together. He diligently read a monthly science magazine for schoolchildren and performed the included experiment kits. He attended medical school in Kobe at his father’s urging and became an orthopedic surgeon, influenced in part by the overtraining injuries he had endured playing judo and rugby. But Yamanaka soon realized that surgery didn’t inspire him. Just as he had been drawn as a boy toward understanding the mechanics of electronics, he was intrigued by basic science and learning how diseases take root.
He earned a Ph.D. in pharmacology at Osaka University and completed a fellowship at the University of California, San Francisco’s Gladstone Institutes. (TIME co-chair and owner Marc Benioff is a past supporter of the Gladstone Foundation.) Yamanaka thrived there, studying a gene that lowered cholesterol in mice and learning how to culture embryonic stem cells in the animals, which served as a foundation for his later discovery.
When his fellowship ended in 1996, Yamanaka returned to Japan. But he missed the scientific community at Gladstone. “I experienced post-America depression,” he says. He had trouble getting funding for his basic research projects and became so disillusioned with his career path in Japan that he considered practicing medicine again, admitting, “I nearly died once as a scientist.”
But an opportunity to run his own lab at Japan’s Nara Institute of Science and Technology provided one last shot at the scientific career he yearned for. “I wanted to try something very big, very risky, but that will have a huge impact on medicine,” he says. “So that’s how I started this project”—his modest way of describing the work that would earn a Nobel Prize.
At the time, other stem-cell scientists were focused on trying to coax embryonic stem cells to become the mature cells the body needs to treat disease—islet cells in the pancreas, for instance, which produce insulin. “I thought I wouldn’t be competitive enough if I just did a similar approach,” he says. So Yamanaka zagged. Rather than starting with embryonic cells, he started with mature, specialized cells and tried to turn them back to an embryo-like state.
There was no guarantee this was even possible with human cells, but Yamanaka pinned his career on two studies that convinced him it might be. First, British biologist John Gurdon, with whom Yamanaka would share the Nobel, had shown in the 1960s that a cell from an already-developed tadpole still contained the genetic instructions it needed to become a new frog. Then, in 1996, Scottish embryologist Ian Wilmut took a mature cell from a female sheep and created an exact clone of the ewe. “Because of those two studies, I thought at least in theory, we could revert somatic [adult] cells back into the embryonic state,” Yamanaka says. “So I was not just a crazy scientist.”
He started by trying to identify which genes were responsible for driving the development of embryonic cells. Then, he used engineered…
Read the original at Time →
Open in TruthVane →