Deregulated miRNAs in Hutchinson-Gilford Progeria Syndrome: Unraveling the Link of miRNAs to normal and premature aging.

Hutchinson-Gilford Progeria Syndrome (HGPS) is a rare, fatal disorder causing premature aging, affecting about 1 in 4–8 million births. Most cases are linked to a mutation in the LMNA gene, which leads to the production of a defective protein called progerin. In HGPS, progerin expression leads to the loss of heterochromatin, which significantly alters gene expression. This alteration particularly affects RNA polymerase II, a crucial enzyme in transcribing primary-miRNA (pri-miRNA) transcripts. As a result, changes in RNA polymerase II activity lead to aberrant levels of miRNAs that are a common feature in age-related diseases, including HGPS, where they contribute to the disease phenotype and progression. In this study, we investigate the molecular mechanisms underlying HGPS and normal aging using global miRNA sequencing to identify differentially expressed miRNAs associated with aging and/or premature aging conditions. Overall design: The sequencing was conducted on 3 control and three HGPS (carrying a mutation on LMNA Exon 11, heterozygous c.1824C > T (p.Gly608Gly)) primary dermal fibroblast cell strains at both a young passage with relative senescence below 5% and an older passage with senescence levels between 15% to 20%.