Cell reprogramming: novel technique turns back the clock on cellular aging
In a world first, researchers from the Babraham Institute (Cambridge, UK) have developed a technique to restore cell function and rejuvenate the molecular measures of biological age. Essentially, the aging process is reversed by 30 years, but cells do not lose their specialized function.
Findings from this study, published in eLife, have convinced the research team that this new technique will revolutionize regenerative medicine. This novel method subjugates the issue of entirely erasing a cells identity by suspending reprogramming part of the way through the process.
The method of converting normal cells into stem cells was first conducted in 2007 by scientist Shinya Yamanaka. The process usually takes around 50 days utilizing key molecules called Yamanaka factors. During the new technique – maturation phase transient reprogramming – skin cells were introduced to Yamanaka factors for 13 days.
Researchers found that age-related changes had been eliminated and the identity of the cells was temporarily removed. These partially reprogrammed cells were then given time to grow under normal conditions, so researchers could observe whether their specific cell function returned.
Genome analysis was carried out and revealed that cells had regained markers characteristic of skin cells (fibroblasts), which was confirmed by observing collagen production in the cells. The research team looked for changes in the hallmarks of aging.
Diljeet Gill, PhD, Epigenetics Programme, Babraham Institute (Cambridge, UK) and co-author of this study, stated: “our understanding of aging on a molecular level has progressed over the last decade, giving rise to techniques that allow researchers to measure age-related biological changes in human cells. We were able to apply this to our experiment to determine the extent of reprogramming our new method achieved.”
The researchers evaluated several measures of cellular age, including the epigenetic clock, whereby chemical tags that are present throughout the genome indicate age. Additionally, the researchers measured the transcriptome, all the gene readouts produced by the cell. According to these measures, the cells matched the profile of cells that were 30 years younger in comparison with reference data sets.
Diljeet claimed: “our results represent a big step forward in our understanding of cell reprogramming. We have proved that cells can be rejuvenated without losing their function and that rejuvenation looks to restore some function to old cells. The fact that we also saw a reverse of aging indicators in genes associated with diseases is particularly promising for the future of this work.”
The research team hope to expand and continue this research. They observed that the technique had an effect the APBA2 gene, associated with Alzheimer’s disease, and the MAF gene, with a role in the development of cataracts, both showed adaptations towards youthful levels of transcription.
The research team do not yet fully understand the precise mechanism behind transient reprogramming, which they hope to explore during further studies. In the future, this novel technique has the potential to expand therapeutic options for various conditions.
Source: Gill D, Parry A, Santos F, et al. Multi-omic rejuvenation of human cells by maturation phase transient reprogramming. eLife doi: 10.7554/eLife.71624 (2022). (Epub ahead of print).