Researchers used adult stem cells from humans and combined experimental techniques with computational approaches to study the changes in the genome associated with aging. They compared freshly isolated human adult stem cells from young individuals, which can self-renew, to cells from the same individuals that were subjected to prolonged passaging in culture. This accelerated model of adult stem cell aging exhausts the regenerative capacity of the adult stem cells. Researchers looked at the changes in genomic sites that accumulate DNA damage in both groups.
"We found the majority of DNA damage and associated chromatin changes that occurred with adult stem cell aging were due to parts of the genome known as retrotransposons," said King Jordan, associate professor in the School of Biology at Georgia Tech.
"Retroransposons were previously thought to be non-functional and were even labeled as 'junk DNA', but accumulating evidence indicates these elements play an important role in genome regulation," he added.
While the young adult stem cells were able to suppress transcriptional activity of these genomic elements and deal with the damage to the DNA, older adult stem cells were not able to scavenge this transcription. New discovery suggests that this event is deleterious for the regenerative ability of stem cells and triggers a process known as cellular senescence.
"By suppressing the accumulation of toxic transcripts from retrotransposons, we were able to reverse the process of human adult stem cell aging in culture," said Lunyak.
"Furthermore, by rewinding the cellular clock in this way, we were not only able to rejuvenate 'aged' human stem cells, but to our surprise we were able to reset them to an earlier developmental stage, by up-regulating the "pluripotency factors" - the proteins that are critically involved in the self-renewal of undifferentiated embryonic stem cells." she said.
Next the team plans to use further analysis to validate the extent to which the rejuvenated stem cells may be suitable for clinical tissue regenerative applications.
Source: Buck Institute for Research on Aging