Werner Syndrome and Hutchinson-Guilford Premature Aging Syndrome are two examples of rare genetic diseases known as Premature Aging Syndrome that cause signs of premature aging in children and young people. Patients with premature aging syndrome usually have pathology and symptoms related to aging, including osteoporosis , cataract , heart disease and type II diabetes . This aging is characterized by a gradual loss of nuclear structure and potential tissue-specific genetic procedures, but the reasons are not yet clear. scientists have discovered a potential new goal to treat these syndromes by preventing nuclear structure loss.
This target is called long scattered repeat sequence -1 (L1) RNA, which is a repeat family , accounting for about 17-20% of the mammalian genome, and its function is basically unknown. The tightly packaged DNA structure , known as heterochromatin, inactive these sequences. There is evidence that during normal aging, depletion of heterochromatin is associated with their activation. "Based on theoretical considerations, we speculate that molecular interactions between L1 RNA and specific enzymes that control heterochromatin stability may be the cause of premature aging in premature aging syndrome," said Francesco Della Valle, a research scientist at King Abdullah University of Science and Technology, who is studying at
. Sequencing studies conducted by
KAUST and the U.S. team showed that L1 RNA expression was higher in cells collected from patients with premature aging syndrome. Further studies have shown that the increase in L1 RNA expression is responsible for the inactivation of an enzyme called SUV39H1, which leads to loss of heterochromatin and changes in gene expression, thereby promoting cell aging.
Francesco Della Valle
Researchers were able to block the expression of L1 RNA and reverse the aging process taken from cells in patients with premature aging syndrome and genetically modified to simulate premature aging mice. They did this with a short synthetic nucleotide strand called antisense oligonucleotide (ASO), which specifically targets and leads to the degradation of L1 RNA. Their L1 ASO is modified to improve its ability to enter the cell and remain stable. Blocking L1 RNA in cells restores heterochromatin and counteracts the genes associated with aging. L1 ASO also extends the lifespan of mice similar to premature aging.
Further studies will need to determine whether other mechanisms that act parallel to SUV39H1 inhibition may impair heterochromatin stability in the syndrome of progestin.
"In other observations, our work has established an important rule," said biological scientist Valerio Orlando. "Contrary to previous thoughts, abnormal expression of L1 RNA is not the result of the onset of aging, but the cause of aging, at least in premature aging. And now, for the first time, we report a specific, rather than a global goal as a fundamental factor of aging."
"Given the similarity between premature aging syndrome and temporal aging-related diseases, targeting LINE-1 RNA may be an effective way to treat premature aging and other age-related diseases characterized by abnormal LINE-1 expression, such as neurodegenerative diseases, metabolic and cardiovascular diseases, and cancer," Orlando said. "This study opens the way for new strategies we believe may help extend human lifespan."
