GoKawiilYuancheng Ryan Lu could barely breathe while he waited for his labmate to adjust the microscope focus.
On the slide in front of them were the results of Lu’s latest attempt to turn back time for ageing retinal nerve cells. If it worked, the method he was using could help to restore eyesight to older adults with glaucoma, an age-related condition that damages the optic nerve. And perhaps some day it could be used to rejuvenate organs such as the kidneys or liver — maybe even the brain.
Longevity is in the genes: half of lifespan is heritable
Lu had spent three years trying different approaches — and had failed. But this time looked different. Lu had introduced three genes into mouse eyes that should revert cells to a younger developmental state. And there under the microscope he thought he could see signs of new growth. Now, he was asking his labmate to confirm his suspicions. “I was so nervous,” says Lu, now a geneticist at the Whitehead Institute in Cambridge, Massachusetts.
When the verdict was in, Lu remembers jumping up and down and high-fiving his colleagues in the microscope room. Yet, he couldn’t help but worry that the celebration might be short-lived.
Lu and his colleagues were among several teams trying to ‘partially reprogram’ cells to a younger state. Now, seven busy years later, his discovery1 is the basis for a clinical trial set to start this year. It will be a pivotal test of a burgeoning field that has attracted researchers in academia and industry — as well as billions of dollars of private investment and the attention of Silicon Valley’s tech elite. The trial will attempt to answer an evocative question: can old cells safely be made young again?
The answer, some say, could reshape the very concept of ageing. It could provide a way to rejuvenate old organs — or, in its most extreme and optimistic formulation, the entire human body. Partial reprogramming also promises to write a new chapter for the foundational discovery, 20 years ago, that adult cells can be reprogrammed to an embryonic-stem-cell-like state2.
But risks loom just as large as the promises: push a cell too close to that stem-like state and it could lose its ability to function properly, and even become cancerous. “When cells lose their identity, we know that comes with some forms of danger,” says Tamir Chandra, who studies ageing at the Mayo Clinic in Rochester, Minnesota.
Rejuvenation factors
In 2006, Shinya Yamanaka, a stem-cell biologist then at Kyoto University in Japan, and his colleague discovered that four proteins known as transcription factors — later dubbed Yamanaka factors — could transform an adult cell into an induced pluripotent stem (iPS) cell that is capable of taking on new identities2. The finding was hailed as breakthrough that could pave the way to stem-cell based therapies in which iPS cells are coaxed into adopting a certain fate and then injected into a patient. In February, regulators in Japan endorsed the approval of the first such iPS-cell-based therapies — for severe heart failure and Parkinson’s disease.
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