Technology may reverse cell aging process, reduce early CVD risk
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Researchers have used RNA therapeutics technology to stimulate telomerase production, which reversed telomere shortening in cells of children with Hutchinson-Gilford progeria syndrome, a condition that causes rapid aging.
“These kids are dying of [MI] and stroke at 13, 14, 15 years old,” John P. Cooke, MD, PhD, department chair of cardiovascular sciences at Houston Methodist Research Institute, said in a press release. “Although current therapies are useful, they only add a year or two, on average, to the child’s life. We wanted to do something that would improve the children’s quality of life and potentially allow them to live longer, so we set about studying their cells and seeing if we could improve the cell function.”
Cooke and colleagues hypothesized that because telomeres are very short in children with progeria, restoring telomere length could improve cell function and possibly reverse the effects of progeria.
“We all have telomere erosion over time, and many of the things that happen to these children at an accelerated pace occur in all of us,” Cooke said in the release. “What we’ve shown is that when we reverse the process of the telomere shortening in the cells from these children and lengthen them, it can reverse a lot of the problems associated with aging.”
Cooke and colleagues transfected 17 progeria fibroblasts with human telomerase messenger RNA or catalytically inactive human telomerase messenger RNA.
Proliferation of progeria cells was poor when untreated or exposed to catalytically inactive human telomerase mRNA, but treatment with active human telomerase mRNA “dramatically increased restored [progeria] cell proliferation, reduced cell loss and extended overall cellular life span,” Cooke and colleagues wrote in a research letter in the Journal of the American College of Cardiology.
“What was most unexpected about our work was the dramatic effect the telomere-extending technology had on the cells,” Cooke said in the release. “We were not expecting to see such a dramatic effect on the ability of the cells to proliferate. They could function and divide more normally, and we gave them extra life span, as well as better function.”
The treatment “was associated with other evidence of cellular rejuvenation” and “did not cause immortalization of the cells because they showed normal growth kinetics, with a log phase of growth followed by a plateau phase,” the researchers wrote. “These studies indicate that transient expression of telomerase mRNA might be a rapid and effective way to reverse senescence in [progeria] cells.”
Cooke said in the release: “Our next steps are to start moving this therapy toward clinical use. We plan to do so by improving existing cell therapies. I want to develop a therapy for these children. It’s an unmet need.” – by Erik Swain
Disclosures: The authors report no relevant financial disclosures.