000089885 001__ 89885
000089885 005__ 20200629140840.0
000089885 0247_ $$2doi$$a10.1186/s12860-017-0147-7
000089885 0248_ $$2sideral$$a108227
000089885 037__ $$aART-2017-108227
000089885 041__ $$aeng
000089885 100__ $$0(orcid)0000-0002-5797-3909$$aLatorre, E
000089885 245__ $$aSmall molecule modulation of splicing factor expression is associated with rescue from cellular senescence
000089885 260__ $$c2017
000089885 5060_ $$aAccess copy available to the general public$$fUnrestricted
000089885 5203_ $$aBackground: Altered expression of mRNA splicing factors occurs with ageing in vivo and is thought to be an ageing mechanism. The accumulation of senescent cells also occurs in vivo with advancing age and causes much degenerative age-related pathology. However, the relationship between these two processes is opaque. Accordingly we developed a novel panel of small molecules based on resveratrol, previously suggested to alter mRNA splicing, to determine whether altered splicing factor expression had potential to influence features of replicative senescence.
Results: Treatment with resveralogues was associated with altered splicing factor expression and rescue of multiple features of senescence. This rescue was independent of cell cycle traverse and also independent of SIRT1, SASP modulation or senolysis. Under growth permissive conditions, cells demonstrating restored splicing factor expression also demonstrated increased telomere length, re-entered cell cycle and resumed proliferation. These phenomena were also influenced by ERK antagonists and agonists.
Conclusions: This is the first demonstration that moderation of splicing factor levels is associated with reversal of cellular senescence in human primary fibroblasts. Small molecule modulators of such targets may therefore represent promising novel anti-degenerative therapies.
000089885 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000089885 590__ $$a2.769$$b2017
000089885 591__ $$aCELL BIOLOGY$$b119 / 190 = 0.626$$c2017$$dQ3$$eT2
000089885 592__ $$a1.277$$b2017
000089885 593__ $$aCell Biology$$c2017$$dQ2
000089885 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000089885 700__ $$aBirar, VC
000089885 700__ $$aSheerin, AN
000089885 700__ $$aJeynes, JCC
000089885 700__ $$aHooper, A
000089885 700__ $$aDawe, HR
000089885 700__ $$aMelzer, D
000089885 700__ $$aCox, LS
000089885 700__ $$aFaragher, RGA
000089885 700__ $$aOstler, EL
000089885 700__ $$aHarries LW
000089885 773__ $$g18, 31 (2017), [15 pp.]$$pBMC CELL BIOL$$tBMC CELL BIOLOGY$$x1471-2121
000089885 8564_ $$s1608315$$uhttps://zaguan.unizar.es/record/89885/files/texto_completo.pdf$$yVersión publicada
000089885 8564_ $$s44097$$uhttps://zaguan.unizar.es/record/89885/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000089885 909CO $$ooai:zaguan.unizar.es:89885$$particulos$$pdriver
000089885 951__ $$a2020-06-29-12:20:35
000089885 980__ $$aARTICLE