Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence
| Autor: | J. Charles C. Jeynes, David Melzer, Amy Hooper, Helen R. Dawe, Eva Latorre, Lynne S. Cox, Vishal C. Birar, Richard G. A. Faragher, Elizabeth L. Ostler, Angela Sheerin, Lorna W. Harries |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
RNA Splicing Factors Senescence MAPK/ERK pathway Biology Small Molecule Libraries 03 medical and health sciences Splicing factor Stilbenes Humans lcsh:QH573-671 Cells Cultured Cellular Senescence Cell Proliferation lcsh:Cytology Alternative splicing Cell Cycle Cell Biology Cell cycle Fibroblasts Cell biology Telomere Ageing Alternative Splicing 030104 developmental biology Resveratrol RNA splicing Research Article |
| Zdroj: | Zaguán: Repositorio Digital de la Universidad de Zaragoza Universidad de Zaragoza Zaguán. Repositorio Digital de la Universidad de Zaragoza instname BMC Cell Biology BMC Cell Biology, Vol 18, Iss 1, Pp 1-15 (2017) |
| Popis: | 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. Electronic supplementary material The online version of this article (10.1186/s12860-017-0147-7) contains supplementary material, which is available to authorized users. |
| Databáze: | OpenAIRE |
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