Father Time may have finally met his match thanks to a new technique that appears to reverse genetic markers of cellular aging. Skin cells from middle-aged donors have been rejuvenated by 30 years, marking a colossal advance for regenerative medicine.
The amazing achievement is described in the eLife review.
As we progress along our life path, our cells undergo age-related genetic changes, resulting in a decrease in their ability to function. This process can be tracked using tools such as epigenetic clocks, which measure the rate of DNA methylation to determine a person’s biological age.
Regenerative biology seeks to erase these markers of aging, restoring cells to a more youthful state. A major breakthrough in this field was made in 2007 when Japanese researcher Shinya Yamanaka developed a technique to transform mature cells into stem cells by exposing them to a cocktail of chemicals – known as Yamanaka factors – for 50 days. .
Unfortunately, this causes the cells to lose their somatic identity, and scientists are unable to reliably cause these reprogrammed stem cells to re-differentiate into mature adult cells. To circumvent this problem, the authors of the new study exposed human skin cells to Yamanaka factors for just 13 days.
This prevented the cells from fully transforming into stem cells, instead causing them to regress only to an intermediate step in the process known as the maturation phase. By this point, many age-related genetic markers had been erased and the cells had temporarily lost their somatic identity, but were able to regain their specialized function as skin cells once the chemicals were removed.
“With our approach, cells temporarily lose their identity as they enter the maturation phase but, importantly, reacquire their initial somatic fate when reprogramming factors are removed,” the researchers write. Although the mechanism behind this identity retrieval is not fully understood, the authors speculate that it may rely on “persistent epigenetic memory” that is not completely erased in the maturation phase.
The technique was applied to skin cells called fibroblasts, which generate collagen and play a crucial role in wound healing. Using cells from three donors aged 38, 53 and 53, the researchers found that their method turned the epigenetic clock of fibroblasts back about thirty years. An analysis of the cells’ transcriptome – encompassing their full set of genetic information – revealed a similar degree of genetic rejuvenation.
Speaking to the BBC, study author Wolf Reik said: “I remember the day I got the results and I didn’t really believe that some of the cells were 30 years younger than they weren’t supposed to be. It was a very exciting day!”
To confirm this result, the researchers simulated a skin wound by making an incision in a layer of treated fibroblasts in a Petri dish. The reprogrammed cells produced a greater amount of collagen than the untreated fibroblasts, while migrating faster in the wound area. All of this points to a significant reversal of age-related functional decline.
On top of all this, the researchers identified signs of rejuvenation in genes with non-fibroblastic functions, such as those associated with Alzheimer’s disease and cataracts.
Unfortunately, the Yamanaka factors are known to interact with certain cancer-related genes, which means this method cannot yet be used to reverse the aging process in living humans. Nevertheless, Reik insists that “this work has very exciting implications” and thinks that future improvements could “open up an incredible therapeutic horizon”.
“Eventually, we may be able to identify genes that rejuvenate without reprogramming, and specifically target those that reduce the effects of aging,” he said in a statement.