Senescent cells cluster CTCF on nuclear speckles to instruct an alternative splicing program

Spiros Palikyras, Vassiliki Varamogiani-Mamatsi, Argyris Papantonis

1. 01

   Nuclear speckle components coordinate CTCF clustering and chromatin rewiring during senescence entry

2. 02

   A senescence-associated alternative splicing programme follows from this reorganisation

3. 03

   Countering the reorganisation delayed senescence entry in model systems

4. 04

   Identifies splicing control as a candidate senomorphic target upstream of the SASP

Study Design

Preclinical Study

Sample Size

Not reported

Study Duration

Not reported

Methodology

Chromatin conformation, nuclear speckle imaging and transcriptomic/splicing analysis in senescence-induced human cell models, with perturbation experiments.

Limitations

Cell-based and preclinical. No in vivo lifespan or healthspan endpoint, no drug-like compound identified, and no human data. Splicing modulators as a class have narrow therapeutic windows.