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Small molecule modulation of splicing factor expression is associated with rescue from cellular senescence
Eva Latorre1, Vishal C Birar2, Angela N Sheerin2
1Institute of Biomedical and Clinical Sciences, University of Exeter Medical School, University of Exeter, Barrack Road, Exeter, Devon, EX2 5DW, UK.
BMC Cell Biology
|October 19, 2017
Summary
Altering mRNA splicing factors can reverse cellular senescence, a key aging mechanism. This finding offers potential for new anti-aging therapies targeting splicing factors.
Area of Science:
- Molecular Biology
- Cellular Senescence
- Aging Research
Background:
- Altered mRNA splicing factor expression is linked to aging.
- Cellular senescence accumulation contributes to age-related diseases.
- The connection between splicing factors and senescence is unclear.
Purpose of the Study:
- To investigate if altered splicing factor expression influences replicative senescence.
- To develop novel small molecules based on resveratrol to modulate splicing factors.
Main Methods:
- Developed resveratrol-based small molecules (resveralogues).
- Treated human primary fibroblasts to assess effects on senescence.
- Analyzed splicing factor expression, cell cycle, telomere length, and proliferation.
Main Results:
- Resveralogues altered splicing factor expression and reversed senescence features.
- Senescence reversal was independent of cell cycle, SIRT1, SASP, or senolysis.
- Restored splicing factor expression led to increased telomere length and proliferation.
Conclusions:
- Demonstrated that modulating splicing factor levels reverses cellular senescence in human fibroblasts.
- Small molecule modulators of splicing factors show promise as anti-degenerative therapies.