Identification and characterization of functional long noncoding RNAs in human fibroblast aging
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE223225 | GEO | 2026/01/17
REPOSITORIES: GEO
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Project description:We established parallel replicative and doxorubicin-induced senescence models in human BJ fibroblasts, demonstrating progressive morphological changes and SA-β-gal activity increases across passages (P3-P33). Molecular analyses confirmed expected senescence markers: p21/p53 upregulation and LMNB1 downregulation at RNA/protein levels. Transcriptomic profiling identified 734 upregulated (extracellular matrix organization) and 195 downregulated (cell cycle) genes. Comparative lncRNA analysis revealed 23 consistently upregulated candidates, with PURPL showing the most dramatic senescence-associated induction. These validated models provide a robust platform for mechanistic aging studies, with PURPL emerging as a key regulator of cellular senescence.
2025-12-02 | GSE301164 | GEO
Project description:ellular senescence is a fundamental driver of aging and age-related diseases, with long non-coding RNAs (lncRNAs) emerging as critical regulators of this process. Here, we identify PURPL as a bidirectional modulator of senescence in human fibroblasts. Through comparative transcriptomic analysis of replicative and doxorubicin-induced senescence models, we discovered PURPL as the most significantly upregulated lncRNA common to both systems. CRISPR interference (CRISPRi)-mediated PURPL depletion in senescent cells reversed hallmark aging phenotypes, including restoration of LMNB1 expression, suppression of p21, and reduced SA-β-gal activity. Conversely, PURPL overexpression in young fibroblasts recapitulated senescence signatures, inducing extracellular matrix reorganization and cell cycle arrest pathways. RNA-seq revealed PURPL overexpression dysregulated 1,633 genes, mirroring natural aging transcriptomes. These opposing effects establish PURPL as a central regulator of cellular senescence, suggesting its therapeutic potential for age-related conditions. Our findings provide mechanistic insights into lncRNA-mediated senescence control and highlight PURPL as a novel target for aging intervention strategies.
2025-12-02 | GSE301166 | GEO
Project description:Cellular senescence is a fundamental driver of ageing and age-related diseases, characterized by irreversible growth arrest and profound epigenetic alterations. While long non-coding RNAs (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.
2025-10-27 | PXD068664 | Pride
Project description:Cellular senescence involves heterochromatin reorganization and aberrant gene expression. We demonstrate that the nuclear-enriched lncRNA PURPL regulates senescence-associated chromatin dynamics by modulating H3K9me3 deposition. PURPL knockdown increased global H3K9me3 levels while its overexpression reduced this repressive mark. Genome-wide analysis revealed 411 loci with PURPL-dependent H3K9me3 changes, including the aging-related gene SERPINE1, where H3K9me3 accumulation correlated with transcriptional repression. These findings establish PURPL as an epigenetic regulator of senescence through targeted control of heterochromatin formation.
2025-12-02 | GSE301169 | GEO
Project description:Increases in age are accompanied by vascular aging, which can lead to a variety of chronic diseases, including atherosclerosis and hypertension. Noncoding RNAs (ncRNAs) have become a research hotspot in different fields of life sciences in recent years. For example, these molecules have been found to have regulatory roles in many physiological and pathological processes. Many studies have shown that microRNAs (miRNAs) and long ncRNAs (lncRNAs) also play a regulatory role in vascular aging. Endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) are important components of blood vessels, and the senescence of both cell types promotes the occurrence of vascular aging. This review provides a contemporary update on the molecular mechanisms underlying the senescence of ECs and VSMCs and the regulatory role of miRNAs and lncRNAs in this process.
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Project description:Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functionally. Here, we sought to identify lncRNAs differentially expressed during replicative senescence. We compared lncRNAs expressed in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those expressed in senescent, late-passage, 'old' fibroblasts (PDL 52) by RNA sequencing (RNA-Seq). Numerous transcripts in all lncRNA groups (antisense lncRNAs, pseudogene-encoded lncRNAs, previously described lncRNAs and novel lncRNAs) were validated using reverse transcription (RT) and real-time, quantitative (q)PCR. Among the novel senescence-associated lncRNAs (SAL-RNAs) showing lower abundance in senescent cells, SAL-RNA1 (XLOC_023166) was found to delay senescence, because reducing SAL-RNA1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive β-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel lncRNAs changes with senescence and suggests that SAL-RNAs play direct regulatory roles in this important cellular process. RNA was extracted from both young and senescent WI-38 cells and used for total RNA-Seq.
2016-02-08 | E-GEOD-77675 | biostudies-arrayexpress
Project description:Noncoding RNAs include small transcripts, such as microRNAs and piwi-interacting RNAs, and a wide range of long noncoding RNAs (lncRNAs). Although many lncRNAs have been identified, only a small number of lncRNAs have been characterized functionally. Here, we sought to identify lncRNAs differentially expressed during replicative senescence. We compared lncRNAs expressed in proliferating, early-passage, 'young' human diploid WI-38 fibroblasts [population doubling (PDL) 20] with those expressed in senescent, late-passage, 'old' fibroblasts (PDL 52) by RNA sequencing (RNA-Seq). Numerous transcripts in all lncRNA groups (antisense lncRNAs, pseudogene-encoded lncRNAs, previously described lncRNAs and novel lncRNAs) were validated using reverse transcription (RT) and real-time, quantitative (q)PCR. Among the novel senescence-associated lncRNAs (SAL-RNAs) showing lower abundance in senescent cells, SAL-RNA1 (XLOC_023166) was found to delay senescence, because reducing SAL-RNA1 levels enhanced the appearance of phenotypic traits of senescence, including an enlarged morphology, positive β-galactosidase activity, and heightened p53 levels. Our results reveal that the expression of known and novel lncRNAs changes with senescence and suggests that SAL-RNAs play direct regulatory roles in this important cellular process.
2016-02-08 | GSE77675 | GEO
Project description:Aging is a process during which progressive deteriorating of cells, tissues, and organs over time lead to loss of function, disease, and death. Towards the goal of extending human health span, there is escalating interest in understanding the mechanisms that govern aging-associated pathologies. Adequate regulation of expression of coding and noncoding genes is critical for maintaining organism homeostasis and preventing disease processes. Long noncoding RNAs (lncRNAs) are increasingly recognized as key regulators of gene expression at all levels--transcriptional, post-transcriptional and post-translational. In this review, we discuss our emerging understanding of lncRNAs implicated in aging illnesses. We focus on diseases arising from age-driven impairment in energy metabolism (obesity, diabetes), the declining capacity to respond homeostatically to proliferative and damaging stimuli (cancer, immune dysfunction), and neurodegeneration. We identify the lncRNAs involved in these ailments and discuss the rising interest in lncRNAs as diagnostic and therapeutic targets to ameliorate age-associated pathologies and prolong health. This article is part of a Special Issue entitled: Clues to long noncoding RNA taxonomy1, edited by Dr. Tetsuro Hirose and Dr. Shinichi Nakagawa.
| S-EPMC4698248 | biostudies-literature
Project description:The goal of our study is to investigate the role of the p53-induced lncRNA PURPL in the context of liver cancer. To achieve this, we identified transcript variants of PURPL expressed in liver cancer cells and assayed for the transcriptome changes caused by PURPL knockdown after p53 induction.
2022-10-18 | GSE206701 | GEO
Project description:The goal of our study is to investigate the role of the p53-induced lncRNA PURPL in the context of liver cancer. To achieve this, we identified transcript variants of PURPL expressed in liver cancer cells and assayed for the transcriptome changes caused by PURPL knockdown after p53 induction.
2022-10-18 | GSE206699 | GEO