89885 20200629140840.0 doi 10.1186/s12860-017-0147-7 sideral 108227 ART-2017-108227 eng (orcid)0000-0002-5797-3909 Latorre, E Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence 2017 Access copy available to the general public Unrestricted Background: Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence. Results: Treatment with resveralogues was associated with altered splicing factor expression and rescue of multiple features of senescence. This rescue was independent of cell cycle traverse and also independent of SIRT1, SASP modulation or senolysis. Under growth permissive conditions, cells demonstrating restored splicing factor expression also demonstrated increased telomere length, re-entered cell cycle and resumed proliferation. These phenomena were also influenced by ERK antagonists and agonists. Conclusions: This is the first demonstration that moderation of splicing factor levels is associated with reversal of cellular senescence in human primary fibroblasts. Small molecule modulators of such targets may therefore represent promising novel anti-degenerative therapies. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 2.769 2017 CELL BIOLOGY 119 / 190 = 0.626 2017 Q3 T2 1.277 2017 Cell Biology 2017 Q2 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Birar, VC Sheerin, AN Jeynes, JCC Hooper, A Dawe, HR Melzer, D Cox, LS Faragher, RGA Ostler, EL Harries LW 18, 31 (2017), [15 pp.] BMC CELL BIOL BMC CELL BIOLOGY 1471-2121 1608315 http://zaguan.unizar.es/record/89885/files/texto_completo.pdf Versión publicada 44097 http://zaguan.unizar.es/record/89885/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:89885 articulos driver 2020-06-29-12:20:35 ARTICLE