A research group from the Buck Institute for Research on Aging and the Georgia Institute of Technology has managed to reverse the aging process for human adult stem cells. Because stem cells are responsible for helping old or damaged tissues regenerate, these findings could lead to medical treatments that repair tissues when they deteriorate as a result of aging. This research was published in the September 1, 2011 edition of the journal Cell Cycle
Aging causes the regenerative power of tissues and organs to wane. The modern-day stem cell hypothesis of aging postulates that living organisms are as old as their tissue-specific (adult) stem cells. This implies that an understanding of the molecules and processes that enable human adult stem cells to initiate self-renewal and to divide, proliferate and subsequently differentiate in order to rejuvenate damaged tissues might be the key to regenerative medicine and an eventual cure for many age-related diseases.
Victoria Lunyak, associate professor at the Buck Institute for Research on Aging, who was involved with this study, 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 keep human tissues healthy by replacing cells that have gotten old or damaged. These same stem cells are “multipotent,” which means that they can grow and replace any number of body cells in the tissue or organ to which they belong. However, just as the cells in the liver, or any other organ, can suffer damaged over time, adult stem cells undergo age-related damage. When this occurs, the body can’t replace damaged tissue as well as it once could, which leads to a host of diseases and conditions. However, if physicians can use procedures and treatments that keep these adult stem cells young, they could possibly use these adult stem cells to repair damaged heart tissue after a heart attack; heal wounds; correct metabolic syndromes; produce insulin for patients with type 1 diabetes; cure arthritis and osteoporosis and regenerate bone.
This research team hypothesized that DNA damage in the genome of adult stem cells would look very different from age-related damage occurring in regular body cells. Bodily cells are known to experience a shortening of the caps found at the ends of chromosomes, known as telomeres. However, adult stem cells are known to maintain their telomeres, and much of the damage in aging is widely thought to be a result of telomere loss. Therefore, there must be different mechanisms in play that are essential to explaining how aging occurs in these adult stem cells, they thought.
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. King Jordan, 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.”
While the young adult stem cells were able to suppress transcriptional activity of these genomic elements and deal with the damage to the DNA. However, older adult stem cells were not able to scavenge this transcription. This new discovery suggests that this event is deleterious for the regenerative ability of stem cells and triggers a process known as cellular senescence. Victoria Lunyak described it this way: “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.”
In the future, 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.