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.
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
David Terraso | EurekAlert!
Don't Give the Slightest Chance to Toxic Elements in Medicinal Products
23.03.2018 | Physikalisch-Technische Bundesanstalt (PTB)
North and South Cooperation to Combat Tuberculosis
22.03.2018 | Universität Zürich
Satellites in near-Earth orbit are at risk due to the steady increase in space debris. But their mission in the areas of telecommunications, navigation or weather forecasts is essential for society. Fraunhofer FHR therefore develops radar-based systems which allow the detection, tracking and cataloging of even the smallest particles of debris. Satellite operators who have access to our data are in a better position to plan evasive maneuvers and prevent destructive collisions. From April, 25-29 2018, Fraunhofer FHR and its partners will exhibit the complementary radar systems TIRA and GESTRA as well as the latest radar techniques for space observation across three stands at the ILA Berlin.
The "traffic situation" in space is very tense: the Earth is currently being orbited not only by countless satellites but also by a large volume of space...
An international team of researchers has discovered a new anti-cancer protein. The protein, called LHPP, prevents the uncontrolled proliferation of cancer cells in the liver. The researchers led by Prof. Michael N. Hall from the Biozentrum, University of Basel, report in “Nature” that LHPP can also serve as a biomarker for the diagnosis and prognosis of liver cancer.
The incidence of liver cancer, also known as hepatocellular carcinoma, is steadily increasing. In the last twenty years, the number of cases has almost doubled...
In just a few weeks from now, the Chinese space station Tiangong-1 will re-enter the Earth's atmosphere where it will to a large extent burn up. It is possible that some debris will reach the Earth's surface. Tiangong-1 is orbiting the Earth uncontrolled at a speed of approx. 29,000 km/h.Currently the prognosis relating to the time of impact currently lies within a window of several days. The scientists at Fraunhofer FHR have already been monitoring Tiangong-1 for a number of weeks with their TIRA system, one of the most powerful space observation radars in the world, with a view to supporting the German Space Situational Awareness Center and the ESA with their re-entry forecasts.
Following the loss of radio contact with Tiangong-1 in 2016 and due to the low orbital height, it is now inevitable that the Chinese space station will...
Fraunhofer Institute for Organic Electronics, Electron Beam and Plasma Technology FEP, provider of research and development services for OLED lighting solutions, announces the founding of the “OLED Licht Forum” and presents latest OLED design and lighting solutions during light+building, from March 18th – 23rd, 2018 in Frankfurt a.M./Germany, at booth no. F91 in Hall 4.0.
They are united in their passion for OLED (organic light emitting diodes) lighting with all of its unique facets and application possibilities. Thus experts in...
A new scenario seeking to explain how Mars' putative oceans came and went over the last 4 billion years implies that the oceans formed several hundred million...
23.03.2018 | Event News
19.03.2018 | Event News
16.03.2018 | Event News
23.03.2018 | Life Sciences
23.03.2018 | Materials Sciences
23.03.2018 | Process Engineering