Aging DNA uncovered
A new paper could upend 20 years of thinking on how stem cells protect their DNA.
Telomeres are protective caps that sit at the end of chromosomes. In adult cells, telomeres shorten each time a cell divides, contributing to ageing and cancer.
Pluripotent stem cells are specialised cells that exist in the earliest days of development. These cells do not age and have the ability to turn into any type of adult cell.
But a surprise new finding shows that telomeres in pluripotent stem cells are protected very differently than telomeres in adult tissues.
“This upends 20 years of thinking on how stem cells protect their DNA,” says Associate Professor Tony Cesare from the University of Sydney.
In adult cells, a protein called TRF2 is essential because it arranges DNA at the chromosome end into a ‘telomere-loop’ structure. Removing TRF2 from adult cells causes the chromosomes to become stitched together into one long string, which is incompatible with life.
To the researchers’ astonishment, removing TRF2 from pluripotent stem cells did almost nothing.
The chromosomes were normal, the telomere-loops remained, and the cells divided as if nothing happened. Telomeres are therefore protected differently in pluripotent stem cells and adult tissues.
This unexpected finding has major implications for research on aging, human development, regenerative medicine, and cancer. Previously, researchers expected fundamental mechanisms that protected DNA would be the same in all tissues. This now appears to be incorrect.
“An exciting outcome of this research is that it definitively shows the critical protective element at chromosome ends is the telomere DNA loop,” said A/Prof Cesare.
“This likely explains why telomere length regulates ageing; cells must need long enough telomeres to make the DNA loops and this becomes difficult as cells age.”
A/Prof Cesare also points out that the discovery is important for understanding stem cells, which are increasingly being used to develop treatments (referred to as regenerative medicine) for many diseases.
“We now realise that the rules for creating telomere loops are entirely different in pluripotent stem cells, suggesting other cellular rules might also be different,” he said.
“This is tremendously exciting for molecular biology and opens up a whole new way of thinking about immortality in stem cells, and invites new research into cancer, aging, embryonic and adult development, and regenerative medicine.”