Explore the vast range of titles available.

Aging is characterized by progressive physiological decline and age‐related pathologies, yet the molecular determinants underlying lineage‐ and species‐specific aging traits remain poorly understood. Although protein‐coding regulators have dominated aging research, the contribution of long non‐coding RNAs (lncRNAs), particularly primate‐specific lncRNAs, has not been systematically explored. Here, through evolutionary screening and cross‐species aging‐associated analyses, we identified a set of primate‐specific lncRNAs (including LINC01021, CTC‐575 l10.1, CTA‐150C2.13, and RP11‐305F18.1, etc.) associated with human aging, and we functionally characterized LINC01021 as a representative candidate to assess their causal involvement. In human cells, LINC01021 promotes cellular senescence, whereas its silencing attenuates senescence‐associated phenotypes. Mechanistically, LINC01021 is predominantly located in the nucleus, where it facilitates DAZAP1‐dependent destabilization of RBMX mRNA, leading to activation of the P53 pathway and induction of canonical senescence features. At the organismal level, ectopic expression of human LINC01021 in mice contributes to aging‐like phenotypes, including increased frailty and impaired motor coordination. Together, these findings implicate primate‐specific lncRNAs in lineage‐restricted aging and highlight an evolutionarily recent regulatory layer that may modulate aging trajectories. Primate‐specific lncRNA LINC01021 promotes aging by enhancing cellular senescence and accelerating aspects of organismal decline. Mechanistically, LINC01021 induces DAZAP1‐mediated destabilization of RBMX, activating the P53 pathway and establishing a primate‐specific regulatory axis in aging.

Background: Loss of the p53-inducible LINC01021 in p53-proficient CRC cell lines results in increased sensitivity to DNA-damaging chemotherapeutics. Here, we comprehensively analyze how LINC01021 affects the p53-induced transcriptional program. Methods: Using a CRISPR/Cas9-approach, we deleted the p53 binding site in the LINC01021 promoter of SW480 colorectal cancer cells and subjected them to RNA-Seq analysis after the activation of ectopic p53. RNA affinity purification followed by mass spectrometry was used to identify proteins associated with LINC01021. Results: Loss of the p53-inducibility of LINC01021 resulted in an ~1.8-fold increase in the number of significantly regulated mRNAs compared to LINC01021 wild-type cells after ectopic activation of p53. A subset of direct p53 target genes, such as NOXA and FAS, displayed significantly stronger induction when the p53-inducibility of LINC01021 was abrogated. Loss of the p53-inducibility of LINC01021 resulted in alternative splicing of a small number of mRNAs, such as ARHGAP12, HSF2, and LYN. Several RNA binding proteins involved in pre-mRNA splicing were identified as interaction partners of LINC01021 by mass spectrometry. Conclusions: Our results suggest that LINC01021 may restrict the extent and strength of p53-mediated transcriptional changes via context-dependent regulation of the expression and splicing of a subset of p53-regulated genes.