Scientists
turn back the clock on adult stem cells
aging
September 21, 2011--Researchers have shown
they can reverse the aging process for human
adult stem cells, which are responsible for
helping old or damaged tissues regenerate.
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 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 are 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 they age.
"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 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.
###
The study was conducted by a team with
members from the Buck Institute for Research
on Aging, the Georgia Institute of
Technology, the University of California,
San Diego, Howard Hughes Medical Institute,
Memorial Sloan-Kettering Cancer Center,
International Computer Science Institute,
Applied Biosystems and Tel-Aviv University.
