American researchers have succeeded in lengthening the telomeres of cells taken from old children. Fighting progeria would therefore be possible.
Therapeutic avenues are multiplying for “old children”. These young patients, suffering from progeria, undergo accelerated aging. They often die before they have blown out their 15 candles. The disease is extremely rare, it affects one in 10 to 20 million births, but several teams are striving to extend their life expectancy.
Among these, researchers from the Houston Methodist Research Institute (United States), who are trying to act on the length of telomeres – a privileged marker of aging. A first study on cells of patients has delivered good results, as they explain in the Journal of the American College of Cardiology.
14 years of life expectancy
Progeria, also known as Hutchinson-Gilford syndrome, is genetic in origin. Due to a mutation in the LMNA gene, the proteins responsible for ensuring the integrity of the nucleus of cells do not function well. One of them, progerin, is particularly toxic, and accumulates in the nucleus of cells from an early age – whereas it normally does not appear until later in life.
Patients therefore suffer from accelerated aging, which results in marked symptoms. Hair loss, cardiovascular disorders, deep wrinkles are all signs that give patients their nickname: old children.
“These children die of a heart attack or stroke at the age of 13, 14 or 15,” said John Cooke, author of this study. Current treatments are helpful, but only extend a child’s life expectancy by a year or two. His team therefore experimented with a new approach: rejuvenating cells, in the hope of limiting the manifestations of progeria.
Lengthen telomeres
Americans have turned their eyes to telomeres, those pieces of non-coding DNA located at the ends of chromosomes, which protect them from damage and mutations. During normal aging, they shorten with age, promoting the appearance of pathologies and reducing life expectancy.
The same process occurs in patients with Hutchinson-Gilford syndrome, but in a much greater way. Of the 17 patients whose cells were analyzed, 12 had severely shortened telomeres. They were comparable to those of a 65-year-old unmoved person.
Once this observation has been made, the scientists have developed a hypothesis: what if lengthening the telomeres made it possible to improve the functioning of cells? In order to test this theory, the team used cells from sick people and put them through a kind of gene therapy, called RNA therapy.
Researchers Develop Technology to Make Aged Cells Younger from Houston methodist we Vimeo.
Reverse aging
In the laboratory, cells with progeria were given RNA that helps synthesize telomerase, a protein that lengthens telomeres. The objective was to stimulate its production. And the approach was successful. Within days, the lifespan and function of diseased cells improved.
“We didn’t expect to see such a strong effect on the ability of cells to proliferate,” says John Cooke. They were able to function and divide in a more normal way, and they were functioning better. “
Cellular markers of aging are also improving. Within a patient, such a method could therefore reduce the severe symptoms of progeria. And offer a complementary mechanism to the other treatments being tested.
In fact, teams – particularly French ones – are currently developing treatments for progeria, but are not targeting telomeres. They try to fight against the accumulation of progerin in cells or to inhibit its production. Which works in part, since the efficacy of metformin has been confirmed in patients and a new molecule has delivered interesting results.
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