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Scientists made a revolutionary discovery 15 years ago when they proved that they could reverse the aging process in cells. Scientists reset the cell’s clock to zero by using four factors called Yamanaka factors discovered by Shinya Yamanaka. A few years later, he was given the Nobel Prize for his work on the factors. For the first time, scientists had hope that aging could be stopped.
“It’s quite incredible when you think about it,” Wolf Reik, who is a molecular biologist at the Babraham Institute in the UK, says of TdR. “You may potentially reverse human cells’ biological age to zero.”
These cells, which had been stripped of aging indicators and deemed to be free of the damage that causes them, might help to heal and rejuvenate injured organs. For example, younger, healthier nerve cells could take the place of brain cells damaged by a stroke, or collagen-enhancing skin cells may be injected into recalcitrant wounds. The only issue is that Yamanaka factors have reset the cells too far back. A cell that is zero days old has no capacity to send an electrical nervous signal or synthesize Collagen; it’s just a mass of potential. It’s like taking a stem cell out for a spin.
To prevent the cell from reverting to its embryonic form, scientists have been experimenting with the timings and looking for methods to halt the reverse-aging process at precisely that point. Although previous attempts in mice were successful, extending the clock just three years, they were not enough.
But now, a research team led by Reik has proven that they can reverse the effects of age on mice by 30 years. It’s the most extreme limit yet achieved. They announced their findings in eLife in April.
“What’s interesting about this research is that they are able to get the cells to reprogram in a time-controlled manner,” says Manuel Serrano, a molecular biologist, who was not involved with the work. Until now, scientists haven’t been able to manage the Yamanaka factors with enough precision, according to Serrano.
Researchers began by collecting skin cells from middle-aged individuals between the ages of 38 and 53. They took skin fibroblast cells, which are vital for wound healing and whose effectiveness decreases with age, as previously stated. The researchers injected the Yamanaka factors (a set of four genes) into the cells using viral vectors, turned them on, and waited. According to previous studies, it takes 50 days for the Yamanaka factors to restart the clock to zero, after which point cell ages range from 20 to 40 years old over a period of 10 days.The researchers halted the action of the Yamanaka factors for this time, assessing the effects on cells between Day 10 and Day 17.
At each pause, scientists measured the biological age of the cells by using molecular “aging clocks.” Epigenetic changes, which cause cancer, were measured. They also observed collagen production since this protein gives young skin its distinct firm and plump texture but decreases with age. They also tracked the mobility of the cells. When skin is injured, fibroblasts migrate into the damaged tissue to begin collagen synthesis and start the healing process. When fibroblasts become older, their activity decreases, which is why aged skin takes longer to heal.
After just 13 days, the scientists discovered the ideal location. The cells were still youthful, though they could still manufacture collagen and move swiftly to damaged sites. “Knowing we had the potential to rejuvenate cells was fantastic,” says Inês Milagre—a scientist at Portugal’s Gulbenkian Institute of Science and one of the study’s authors. “But the most interesting thing was seeing that the cells were functionally younger.”
According to Milagre, the accomplishment is a significant step forward in proving that Yamanaka factors can be fine-tuned. She does not anticipate the method to be offered in clinics anytime soon, however. The activation of the Yamanaka factors has been linked with cancer, and it’s still unclear whether this technique will work in other types of cells. “There are still so many unanswered questions,” she adds.
