As we get older, our body’s ability to regenerate tissues and organs declines. Scientists believe we are as old as our tissue specific or adult stem cells are. Understanding the molecules and processes that allow human adult cells to start regenerating and dividing, proliferating and eventually differentiating in order to replace damaged tissue could be crucial to regenerative medicine, the authors explain. Understanding the process would help us eventually find cures for several age-related illnesses.
In this study, the scientists set out to determine what goes wrong with the biological clock that undermines the division of human adult stem cells as we get older.
Victoria Lunyak, Ph.D., associate professor at the Buck Institute for Research on Aging, said:
“We demonstrated that we were able to reverse the process of aging for human adult stem cells by intervening with the activity of non-protein coding RNAs originated from genomic regions once dismissed as non-functional ‘genomic junk’.”
Adult stem cells are important for several reasons:
- They replace cells that have become old or damaged – thereby keeping human tissues healthy
- They can grow and replace a wide range of body cell types – they are multipotent, they can replace damaged parts of various organs
The problem is that adult stem cells become damaged themselves as we age – they undergo age-related damage, making it more difficult for the body to replace damaged tissue. This gradual loss in the ability to replace damaged cells, leads to a host of conditions and diseases.
If we could find a way of preventing the adult stem cells from aging, they could repair, for example, heart tissue after a heart attack, heal wounds effectively, produce insulin for individuals with diabetes type 1, cure osteoporosis and arthritis by regenerating bone.
Lunyak and team hypothesized that DNA damage in adult cells’ genome would be quite different from damage related to aging that occurs in regular body cells. The telomeres in body cells get shorter as we age (caps at the ends of chromosomes), while telomeres in adult stem cells are not affected. As most of our understanding regarding aging relates to the loss of telomeres, the authors believed that how aging occurs in adult stem cells follows an entirely different mechanism.
They utilized adult stems and used computational approaches to examine the alterations linked to aging that occur in their genome.
Freshly isolated adult cells gathered from young humans were compared to other stem cells that had been subjected to prolonged passaging in culture – put simply, they compared freshly gathered young adult stem cells to ones that had aged. They observed the changes in the genomic sites in both groups where DNA damage builds up.
King Jordan, Ph.D., associate professor in the School of Biology at Georgia Tech, said:
“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.
“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.
They found that the young adult stem cells managed to suppress the transcriptional activity of those genomic elements, thus solving any DNA damage. However, the older adult stem cells did not manage to scavenge this transcription. They found that this event seriously undermines the adult stem cells’ ability to regenerate, as well as triggering cellular senescence. Cellular senescence is when cells lose their ability to divide or replicate.
“By suppressing the accumulation of toxic transcripts from retrotransposons, we were able to reverse the process of human adult stem cell aging in culture.
“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.”
The authors say they now plan to find out to what extent rejuvenated stem cells can be used for clinical tissue regenerative applications.
Written by Christian Nordqvist