Scientists turn back the clock on adult stem cells aging

September 20, 2011, Georgia Institute of Technology

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 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 underlying the limited division of human adult stem cells as they .

"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 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 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 may be suitable for clinical tissue regenerative applications.

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

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13 comments

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210
5 / 5 (4) Sep 20, 2011
Holy Cow! This is some major crap! Could this be the century that we really deal a death blow to...death?
Probably not, someone will decide to start another war to fix the worlds economic issues and funding for research will dry up again and the researchers will end up working at Walmart or MacDonalds and living in their dead parents basements...shucks!
word-
Dug
4.4 / 5 (10) Sep 20, 2011
Hey anti-aging research guys - just remember some of us out here are dying while you're making sure you understand all there is to know about genetic age cascade events. How about moving it along so we don't have to come back and haunt your sorry asses. Could be a long metaphysical hassle if you get to be immortal and we don't. Just sayin.
XQuantumKnightX
3.7 / 5 (3) Sep 20, 2011
Ok why don't the gov fund this research so that humanity can fix the biggest problem man has face. Death. If I had the money I would invest 100 billion dollars to bring this miracle to the masses!
XQuantumKnightX
3 / 5 (2) Sep 20, 2011
This should be all over the news and be our number 1 priority!
dsl5000
5 / 5 (1) Sep 20, 2011
if this can reduce/ suppress toxic accumulation of retrotransposons transcripts....i wonder what effects it would have on cancerous cells. Especially if it can deal with DNA damage.

Are they really saying that they've found a way to get around the hayflick limit? yet maintain normal cell function?
gmurphy
not rated yet Sep 21, 2011
As exciting as this news is, I believe it only applies to stem cells, I'm not sure if the same effect can be applied to normal cells, fingers crossed! :)
LivaN
5 / 5 (3) Sep 21, 2011
Ok why don't the gov fund this research so that humanity can fix the biggest problem man has face. Death. If I had the money I would invest 100 billion dollars to bring this miracle to the masses!

Put me down for 100 billion too! Truly nothing would so benefit humanity than preventing age related death.
Nemo
2 / 5 (5) Sep 21, 2011
Sounds like a bad idea to me if it means more people on the planet. We need less. I've always figured 1 billion was about the sustainable limit.

If this discovery means a healthier life during the normal lifespan I'm all for it.
LivaN
4.6 / 5 (5) Sep 21, 2011
Sounds like a bad idea to me if it means more people on the planet. We need less.


As far as bad ideas go, allowing millions of deaths each year is far worse than having to revise laws and measures to accommodate the population size for a never aging society.
XQuantumKnightX
1.8 / 5 (5) Sep 21, 2011
Sounds like a bad idea to me if it means more people on the planet. We need less. I've always figured 1 billion was about the sustainable limit.

If this discovery means a healthier life during the normal lifespan I'm all for it.


Wow are you serious? Have the planet ever been over populated? Does over population of earth even makes sence? Also, do you realize that mans strength is in our numbers and that our true destiny is not to remain in our egg and home called earth. Our destiny is not status Quo it's it is expand into space and become more like our creator! There is so much to experience, learn and discover where 80 years is not enough time at all!
Giacomo11-02-58
1 / 5 (3) Sep 25, 2011
Are you guys nuts? "Could this be the century that we really deal a death blow to...death?". Don't you maniacs realize that we need to make room for our own children? God bless death. Plus, do you really think that the death blow to death would get published in Cell Cycle, respectfully speaking?
Skultch
5 / 5 (3) Sep 25, 2011
Are you guys nuts? "Could this be the century that we really deal a death blow to...death?". Don't you maniacs realize that we need to make room for our own children? God bless death. Plus, do you really think that the death blow to death would get published in Cell Cycle, respectfully speaking?


No. Are you? You don't not solve a problem because it will make another one worse. You try to solve BOTH, which is exactly what we humans are doing. Sure, there might be issues to be dealt with between breakthroughs, but technological history has shown that every one leads to another. Your apparent "method" would slow progress to a near halt; "taking one thing at a time, in order." Try to have a little more imagination in our abilities as a cooperating society.

The "death blow to death" will be gradual up until we actually start reversing aging.
ED__269_
5 / 5 (1) Sep 27, 2011
@ Skultch.

Admirable sentiment.

Your faith in mankind is greater than my present level.

I recall ex-pres Bush's statement regarding potential action against a shrinking radius - and runaway global warming...
"we can barely make it to the moon..."

My own government just passed a law 2 days ago that will probably further infringe on the freedoms of the individual by allowing for the provision of videoing of people without their consent.

its a messy world, but in principle, I agree with you. In actuality, I bet some of MONEY is highly self serving and thinks life is cheap.

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