Father Time may finally have met his match thanks to a new technique that appears to reverse the genetic markers of cellular aging. Skin cells of middle-aged donors were rejuvenated by 30 years, marking a colossal step forward for regenerative medicine. The astonishing achievement is described in the journal eLife. As we progress along our life path, our cells undergo age-related genetic modifications, resulting in a decrease in their ability to function. This process can be tracked using tools like 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 within this field was achieved in 2007 when Japanese researcher Shinya Yamanaka developed a technique to turn mature cells back into stem cells by exposing them to a cocktail of chemicals – known as the Yamanaka factors – for 50 days. Unfortunately, however, this causes cells to lose their somatic identity, and scientists are unable to reliably coax these reprogrammed stem cells into re-differentiating into mature adult cells. To get around this problem, the authors of the new study exposed human skin cells to the Yamanaka factors for just 13 days. This prevented the cells from fully reverting to stem cells, causing them instead to regress only to an intermediate stage in the process known as the maturation phase. At this point, many of the age-related genetic markers had been erased and the cells had temporarily lost their somatic identity, yet were able to re-acquire 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enter the maturation phase but, importantly, reacquire their initial somatic fate when the reprogramming factors are withdrawn,” write the researchers. While the mechanism behind this retrieval of identity is not fully understood, the authors speculate that it may rely on “persisting epigenetic memory” that is not fully erased in the maturation phase. The technique was applied to skin cells called fibroblasts, which generate collagen and play a crucial role in wound repair. Using cells from three donors aged 38, 53, and 53, the researchers found that their method wound back the fibroblasts’ epigenetic clock by approximately 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 back and I didn't quite believe that some of the cells were 30 years younger than they were supposed to be. It was a very exciting day!" To confirm this finding, the researchers simulated a skin wound by making a cut in a layer of treated fibroblasts in a petri dish. The reprogrammed cells produced a greater quantity of collagen than untreated fibroblasts, while also migrating into the wound area more rapidly. This all 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-fibroblast functions, such as those that are associated with Alzheimer’s and cataracts. Unfortunately, the Yamanaka factors are known to interact with certain genes linked to cancer, meaning this method can’t be used to reverse the aging process in living humans just yet. Nonetheless, Reik insists that "this work has very exciting implications,” and believes future improvements could “open up an amazing therapeutic horizon.” “Eventually, we may be able to identify genes that rejuvenate without reprogramming, and specifically target those to reduce the effects of aging,” he said in a statement. Source
