Authors: Juan Carlos Izpisua Belmonte, Francesco della Valle, Pradeep Reddy, Mako Yamamoto, Peng Liu, Alfonso Saera-Vila, Dalila Bansaddek, Huoming Zhang, Javier Prieto Martinez, Leila Abassi, Mirko Celii, Alejandro Ocampo, Estrella Nuñez Delicado, Arianna Mangiavacchi, Riccardo Aiese Cigliano, Conception Rodriguez Esteban, Steve Horvath, Valerio Orlando.
- King Abdullah University of Science and Technology (KAUST), Saudi Arabia
- Salk Institute for Biological Studies, La Jolla, CA, USA
- Sequentia Biotech, Barcelona, Spain
Publication: Science Translational Medicine
Date: August, 2022
Link: LINE-1 RNA causes heterochromatin erosion and is a target for amelioration of senescent phenotypes in progeroid syndromes
Heterochromatin condensation suppresses repetitive and transposable elements, including long interspersed nuclear element (LINE) retrotransposons, but is lost during aging, leading to derepression of these LINE elements. However, the consequences of this derepression are not fully understood. Here, Della Valle et al. studied LINE-1 in typical and atypical progeroid syndromes. Nuclear LINE-1 RNA expression occurred early in progeroid cells, resulting in suppression of the histone-lysine N-methyltransferase SUV39H1 activity, leading to heterochromatin loss and senescent phenotypes. Depletion of LINE-1 RNA using antisense oligonucleotides restored heterochromatin epigenetic marks and decreased the expression of senescence-associated genes in human cells and in a mouse model of Hutchinson-Gilford progeria syndrome, resulting in increased life span. These findings suggest LINE-1 RNA as a therapeutic target for premature aging syndromes.