Scientists from the UK’s Babraham Institute near Cambridge say they have developed a new technique for rejuvenating skin cells, allowing them "to rewind the cellular biological clock by around 30 years".
The technique enabled them to 'time jump' human skin cells, turning back the ageing clock without losing the cells’ specialised function. Although it’s early days, the research, published in the journal eLife , holds out the promise that "it could revolutionise regenerative medicine", they said.
With age, cells' ability to function declines and the genome accumulates marks of ageing. Reprogramming somatic cells in a series of steps, each erasing some of the marks that make cells specialised, can create induced pluripotent stem cells and reverse these age-associated changes, but during the process somatic cell identity is lost.
While stem cells in theory have the potential to become any cell type, scientists haven’t yet been able to re-differentiate stem cells into all cell types; instead, re-differentiated induced pluripotent stem cells often resemble foetal rather than mature adult cells.
Time To 'Reprogramme' Stem Cells Cut to 13 Days
The team’s new method overcomes this by halting reprogramming part of the way through the process, enabling them to find the precise balance between making cells biologically younger and regaining their specialised cell function.
The technique, called 'maturation phase transient reprogramming’ (MPTR), cut the process of stem cell reprogramming from around 50 days to just 13 days, at which point age-related changes had been removed and the cells had temporarily lost their identity. These partly-reprogrammed cells were then allowed to grow under normal conditions.
The technique was tested on dermal fibroblasts from middle-aged donors, and the researchers found that the cells reacquired their identity lost during MPTR. Genome analysis showed that they had regained markers characteristic of fibroblasts.
"Excitingly, our method substantially rejuvenated multiple cellular attributes, including the transcriptome, which was rejuvenated by around 30 years as measured by a novel transcriptome clock," the authors said.
The epigenome was rejuvenated to a similar extent. This magnitude of rejuvenation "appears substantially greater than that achieved in previous transient reprogramming protocols", they said.
Understanding Of Ageing has Progressed Over the Last Decade
Dr Diljeet Gill, a postdoctoral researcher at the Institute and lead author on the paper, said: "Our understanding of ageing 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 potential applications of this technique are dependent on the cells not only appearing younger, but regaining youthful functioning too. The team were able to show that the reprogrammed fibroblasts produced youthful levels of collagen proteins, compared with control cells. They also showed partial functional rejuvenation of their migration speed in an in vitro experimental wound, "a promising sign that one day this research could eventually be used to create cells that are better at healing wounds", they said.
Even more exciting therapeutic possibilities may open up in future. The researchers also observed that MPTR had an effect on other genes linked to age-related diseases, including the APBA2 gene, associated with Alzheimer’s disease, and the MAF gene that plays a role in the development of cataracts: both showed changes towards youthful levels of transcription.
Dr Gill concluded: "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 ageing indicators in genes associated with diseases is particularly promising for the future of this work."
Professor Wolf Reik, who led the research, said: "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 ageing. This approach holds promise for valuable discoveries that could open up an amazing therapeutic horizon."
Funding for the study came from the Biotechnology and Biological Sciences Research Council, the Milky Way Research Foundation, and the Wellcome Trust.
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