Researchers have shown they can reverse the aging process forhuman adult stem cells, which are responsible for helping old or damagedtissues regenerate. The findings could lead to medical treatments that mayrepair a host of ailments that occur because of tissue damage as people age. Aresearch group led by the Buck Institute for Research on Aging and the GeorgiaInstitute of Technology conducted the study in cell culture, which appears inthe September 1, 2011 edition of the journal Cell Cycle.

Theregenerative power of tissues and organs declines as we age. The modern daystem cell hypothesis of aging suggests that living organisms are as old as are itstissue specific or adult stem cells. Therefore, an understanding of themolecules and processes that enable human adult stem cells to initiateself-renewal and to divide, proliferate and then differentiate in order torejuvenate damaged tissue might be the key to regenerative medicine and an eventualcure for many age-related diseases. A research groupled by the Buck Institute for Research on Aging in collaboration with the Georgia Institute of Technology, conducted the study thatpinpoints what is going wrong with the biological clock underlying the limited division ofhuman adult stem cells as they age.

“Wedemonstrated that we were able to reverse the process of aging for human adultstem cells by intervening with the activity of non-protein coding RNAs originated fromgenomic regions once dismissed as non-functional  ‘genomic junk’,” said Victoria Lunyak, associate professor at the Buck Institutefor Research on Aging.

Adultstem cells are important because they help keep human tissues healthy byreplacing cells that have gotten old or damaged. They’re also multipotent,which means that an adult stem cell can grow and replace any number of bodycells in the tissue or organ they belong to. However, just as the cells inthe liver, or any otherorgan, can get damaged over time, adult stem cells undergo age-related damage. And when this happens, the bodycan’t replace damaged tissue as well as it once could, leading to a host of diseasesand conditions. But if scientists can find a way to keep these adult stem cellsyoung, they could possibly use these cells to repair damaged heart tissue aftera heart attack; heal wounds; correct metabolic syndromes; produce insulin forpatients with type 1 diabetes; cure arthritis and osteoporosis and regeneratebone.

Theteam began by hypothesizing that DNA damage in the genome of adult stem cells wouldlook very different from age-related damage occurring in regular body cells. They thoughtso because body cells are known to experience a shortening of the caps found atthe ends of chromosomes, known as telomeres. But adult stem cells are known tomaintain their telomeres. Much of the damage in aging is widely thought to be aresult of losing telomeres. So there must be different mechanismsat play that arekey to explaining how aging occurs in these adult stem cells, they thought.

Researchersused adult stem cells from humans and combined experimental techniques withcomputational approaches to study the changes in the genome associated withaging.  They compared freshly isolated human adult stem cells from young individuals, which canself-renew, to cellsfrom the same individuals that were subjected to prolonged passaging inculture. This accelerated model of adult stem cell aging exhausts the regenerativecapacity of the adult stem cells. Researchers looked at the changes in genomic sites that accumulateDNA damage in both groups.

“Wefound the majority of DNA damage and associated chromatin changes that occurredwith 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.

“Retroransposonswere previously thought to be non-functional and were even labeled as ‘junk DNA’, but accumulating evidenceindicates these elements play an important role in genome regulation,” headded.

Whilethe young adult stem cells were able to suppress transcriptional activity ofthese genomic elements and deal with the damage to the DNA, older adult stem cells werenot able to scavenge this transcription. New discovery suggests that this event is deleteriousfor the regenerativeability of stem cells and triggers a process known as cellular senescence.

“Bysuppressing the accumulation of toxic transcripts from retrotransposons, wewere 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 torejuvenate ’aged’ human stem cells, but to our surprise we were able to resetthem to an earlier developmental stage, by up-regulating the “pluripotency factors” – the proteinsthat are critically involved in the self-renewal of undifferentiated embryonicstem cells.” she said.

Nextthe team plans to use further analysis to validate the extent to which therejuvenated stem cells may be suitable for clinical tissue regenerativeapplications.

Thestudy was conducted by a team with members from the Buck Institute for Researchon Aging, the Georgia Institute of Technology, the University of California,San Diego, Howard Hughes Medical Institute, Memorial Sloan-Kettering CancerCenter, International Computer Science Institute, Applied Biosystems andTel-Aviv University.

Citation:
Inhibitionof activated pericentromeric SINE/Alu repeat transcription in senescent human
adult stem cells reinstates self-renewal.  Cell Cycle, Volume 10, Issue 17, September 1, 2011

Written byDavid Terraso, Georgia Tech/Kris Rebillot, Buck Institute