Targeting PURPL RNA enabled rejuvenation of senescence cells via epigenetic reprogramming
Jie Wang1, Xiao Yang1, Xinyu Su1
1Ministry of Education Key Laboratory of Resource Biology and Biotechnology in Western China, Shaanxi Provincial Key Laboratory of Biotechnology, College of Life Sciences, Northwest University, Xi'an, 710069, China.
Journal of Translational Medicine
|October 17, 2025
Summary
Scientists discovered the ageing-associated long non-coding RNA PURPL regulates cellular rejuvenation. Depleting PURPL reversed ageing markers, while its overexpression accelerated senescence, revealing its therapeutic potential.
Area of Science:
- Epigenetics
- Molecular Biology
- Gerontology
Background:
- Cellular senescence drives aging and age-related diseases.
- Long non-coding RNAs (lncRNAs) regulate senescence.
- The role of lncRNAs in cellular rejuvenation is unknown.
Purpose of the Study:
- Identify lncRNAs involved in cellular rejuvenation.
- Investigate the epigenetic mechanisms of senescence regulation by lncRNAs.
- Explore PURPL as a therapeutic target for age-related diseases.
Main Methods:
- CRISPR interference (CRISPRi) for PURPL depletion.
- Assessed cell morphology, senescence markers (p21, SA-β-gal), and gene expression.
- Investigated H3K9me3 deposition and transcriptional regulation at specific loci.
Main Results:
- PURPL depletion led to cellular rejuvenation, restoring youthful morphology and suppressing senescence markers.
- PURPL overexpression accelerated cellular senescence, mimicking aging hallmarks.
- PURPL epigenetically regulates H3K9me3 deposition at 411 loci, including senescence drivers SERPINE1 and EGR1.
Conclusions:
- PURPL is an ageing-associated lncRNA that epigenetically modulates cellular senescence via H3K9me3.
- PURPL controls cellular rejuvenation by repressing senescence-associated genes.
- PURPL represents a potential therapeutic target for age-related pathologies.
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