Journal of translational medicineOct 17, 2025

Reversing aging in old cells by targeting PURPL RNA through gene activity changes

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Essence

PURPL lncRNA appears to help maintain senescent-cell programs through H3K9me3-linked transcriptional control.

Evidence

Cell-based CRISPRi and overexpression experiments in senescent cells linked PURPL depletion to youthful morphology and lower p21 and SA-beta-gal, while PURPL overexpression accelerated senescence-like transcriptional and phenotypic changes.

Caveat

The findings come from cell models and marker or genomic endpoints, so they do not establish organism-level rejuvenation or therapeutic benefit in age-related disease.

Simplified

is a fundamental driver of ageing and age-related diseases, characterized by irreversible growth arrest and profound epigenetic alterations. While (lncRNAs) have emerged as key regulators of senescence, their potential for senescent cell rejuvenation remains unexplored. Here, we identify the ageing-associated lncRNA PURPL as an epigenetic regulator that controls cellular rejuvenation through H3K9me3-mediated transcriptional silencing. CRISPRi-mediated PURPL depletion produces striking rejuvenation effects, resulting in restored youthful cell morphology, as well as suppression of senescence markers such as p21 and SA-β-gal. Conversely, PURPL overexpression accelerates cellular senescence, recapitulating the transcriptional and phenotypic hallmarks of ageing. Mechanistically, nuclear-localized PURPL regulates H3K9me3 deposition at 411 genomic loci including SERPINE1 (PAI-1) and EGR1, which are key senescence drivers. PURPL-mediated H3K9me3 loss at these loci derepresses their transcription, establishing a pro-senescence gene expression program. These findings reveal that PURPL is an epigenetic modulator of senescence and highlight its potential as a therapeutic target for age-related pathologies.