For their trial run of the new test, dubbed addition of de novo initiated telomeres (ADDIT), Greider's group examined an enzyme called ATM kinase. "ATM kinase was known to be involved in DNA repair, but there were conflicting reports about whether it had a role in telomere lengthening," says Greider. Her team blocked the enzyme in lab-grown mouse cells, and used ADDIT to find that it was indeed needed to lengthen telomeres. They verified the result using the old, three-month-long telomere test, and got the same result.
The team also found that in normal mouse cells, a drug that blocks an enzyme called PARP1 would activate ATM kinase and spur telomere lengthening. This finding offers a proof of principle for drug-based telomere elongation to treat short-telomere diseases, such as bone marrow failure, Greider says -- but she cautions that PARP1 inhibitor drug itself doesn't have the same telomere-elongating effect in human cells as it does in mouse cells.
Greider's group plans to use ADDIT to find out more about the telomere-lengthening biochemical pathway that ATM kinase is a part of, as well as other pathways that help determine telomere length. "The potential applications are very exciting," Lee says. "Ultimately ADDIT can help us understand how cells strike a balance between aging and the uncontrolled cell growth of cancer, which is very intriguing."
Owen R. Fonorow, Follow #OWENRFONOROW at twitter