Aging of adult stem cells can be reversed
21 September 2011
The aging process for human adult stem cells can be reversed
by adjusting areas of DNA thought to be 'junk'. Adult stem cells are
responsible for helping old or damaged tissues regenerate, so it is
hoped that the findings could lead to medical treatments that may repair
a host of ailments that occur because of tissue damage as people age.
A research group led by the Buck Institute for Research on Aging and
the Georgia Institute of Technology in the US conducted the study in
cell culture, which appears in the September 1, 2011 edition of the
journal Cell Cycle.
The regenerative power of tissues and organs declines as we age. The
modern day stem cell hypothesis of aging suggests that living
organisms are as old as its tissue specific or adult stem cells.
Therefore, an understanding of the molecules and processes that
enable human adult stem cells to initiate self-renewal and to
divide, proliferate and then differentiate in order to rejuvenate
damaged tissue might be the key to regenerative medicine and an
eventual cure for many age-related diseases.
A research group led by the Buck Institute for Research on Aging in
collaboration with the Georgia Institute of Technology, conducted
the study that pinpoints what is going wrong with the biological
clock underlying the limited division of human adult stem cells as
“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’,” said Victoria Lunyak,
associate professor at the Buck Institute for Research on Aging.
Adult stem cells are important because they help keep human tissues
healthy by replacing 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 body cells in the tissue or organ they belong
to. However, just as the cells in the liver, or any other organ, can
get damaged over time, adult stem cells undergo age-related damage.
And when this happens, the body can’t replace damaged tissue as well
as it once could, leading to a host of diseases and conditions. But
if scientists can find a way to keep these adult stem cells young,
they could possibly use these 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.
The team began by hypothesizing that DNA damage in the genome of
adult stem cells would look very different from age-related damage
occurring in regular body cells. They thought so because body cells
are known to experience a shortening of the caps found at the ends
of chromosomes, known as telomeres. But adult stem cells are known
to maintain their telomeres. Much of the damage in aging is widely
thought to be a result of losing telomeres. So there must be
different mechanisms at play that are key 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.
“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
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.