Old human cells return to a more youthful and vigorous state after being induced to briefly express a panel of proteins involved in embryonic development, according to a new study by researchers at the Stanford University School of Medicine.
The researchers also found that elderly mice regained youthful strength after their existing muscle stem cells were subjected to the rejuvenating protein treatment and transplanted back into their bodies. The proteins, known as Yamanaka factors, are commonly used to transform adult cells into induced pluripotent stem cells, or iPS cells.
The study found that inducing old human cells in a lab dish to briefly express these proteins rewinds many of the molecular hallmarks of aging and renders the treated cells nearly indistinguishable from their younger counterparts.
"When iPS cells are made from adult cells, they become both youthful and pluripotent," said Vittorio Sebastiano, Ph.D., senior author of a paper published in Nature Communications today. "We've wondered for some time if it might be possible to simply rewind the aging clock without inducing pluripotency. Now we've found that, by tightly controlling the duration of the exposure to these protein factors, we can promote rejuvenation in multiple human cell types."
Researchers in Sebastiano's laboratory make iPS cells from adult cells, such as those that compose skin, by repeatedly exposing them over a period of about two weeks to a panel of proteins important to early embryonic development. They do so by introducing daily, short-lived RNA messages into the adult cells. The RNA messages encode the instructions for making the Yamanaka proteins. Over time, these proteins rewind the cells' fate—pushing them backward along the developmental timeline until they resemble the young, embryonic-like pluripotent cells from which they originated.
During this process the cells not only shed any memories of their previous identities, but they revert to a younger state. They accomplish this transformation by wiping their DNA clean of the molecular tags that not only differentiate, say, a skin cell from a heart muscle cell, but of other tags that accumulate as a cell ages.