RESEARCH HAS developed a method to turn back the aging clock for cells for 30 years without losing their specialized function. Work by researchers has been able to partly restore the function of older cells, as well as rejuvenating the molecular measures of biological age.
As we age, our cells’ ability to function declines. Regenerative biology aims to repair or replace cells including old ones. One of the most important tools in regenerative biology is our ability to create ‘induced’ stem cells. In theory, these stem cells have the potential to become any cell type.
The new cell identity halt reprogramming part of the way through the process. This allowed researchers to find the precise balance between reprogramming cells, making them biologically younger, while still being able to regain their specialized cell function.
Shinya Yamanaka was the first scientist to turn normal cells, which have a specific function, into stem cells which have the special ability to develop into any cell type. The full process of stem cell reprogramming takes around 50 days using four key molecules called the Yamanaka factors. The new method, called ‘maturation phase transient reprogramming’, exposes cells to Yamanaka factors for just 13 days. The partly reprogrammed cells were given time to grow under normal conditions, to observe whether their specific skin cell function returned. Genome analysis showed that cells had regained markers characteristic of skin cells (fibroblasts).
To show that the cells had been rejuvenated, the researchers looked at multiple measures of cellular age. The first is the epigenetic clock, where chemical tags present throughout the genome indicate age. The second is the transcriptome, all the gene readouts produced by the cell. By these two measures, the reprogrammed cells matched the profile of cells that were 30 years younger compared to reference data sets.
The potential applications of this technique are dependent on the cells not only appearing younger, but functioning like young cells too. Fibroblasts produce collagen, a molecule found in bones, skin tendons and ligaments, helping provide structure to tissues and heal wounds. The rejuvenated fibroblasts produced more collagen proteins compared to control cells that did not undergo the reprogramming process.
Fibroblasts also move into areas that need repairing. Researchers tested the partially rejuvenated cells by creating an artificial cut in a layer of cells in a dish. They found that their treated fibroblasts moved into the gap faster than older cells. This is a promising sign that one day this research could eventually be used to create cells that are better at healing wounds. This work has very exciting implications. Eventually, we may be able to identify genes that rejuvenate without reprogramming, and specifically target those to reduce the effects of aging. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon. By Manny Palomar, PhD (EV Mail August 22-28, 2022 issue)
