Biogerontology · Nov 9, 2026
The lncRNA SEPT5-GP1BB-encoded peptide ARP, upregulated by 17β-estradiol, retards H2O2-induced senescence of human umbilical vein endothelial cells by promoting autophagy
By Wei W, Song S, Xie L et al.
Vascular endothelial cell (VEC) senescence is a key contributor to vascular aging and atherosclerosis. Increasing evidence suggests that long non-coding RNAs (lncRNAs) can encode functional micropeptides involved in cellular regulation. In this study, we investigated whether 17β-estradiol (17β-E2) delays endothelial senescence through an lncRNA-encoded peptide associated with autophagy. RNA sequencing was performed in H₂O₂-induced senescent human umbilical vein endothelial cells (HUVECs) treated with or without 17β-E2, and differentially expressed lncRNAs with coding potential were identified through GO/KEGG analyses and bioinformatics prediction. LncRNA SEPT5-GP1BB was found to encode a 453-amino-acid peptide termed ARP, whose expression was reduced during endothelial senescence but restored by 17β-E2 treatment. Functional experiments demonstrated that 17β-E2 promoted autophagy through ARP rather than through the lncRNA transcript itself. ARP overexpression increased LC3B expression, reduced p62 accumulation, decreased senescence-associated β-galactosidase activity, suppressed SASP-related gene expression, and alleviated oxidative stress in senescent HUVECs. Furthermore, these protective effects were largely abolished by chloroquine treatment, indicating that autophagy mediated the anti-senescent effects of ARP. Collectively, these findings demonstrate that 17β-E2 delays endothelial senescence by upregulating the lncRNA SEPT5-GP1BB-encoded peptide ARP, which promotes autophagy, suggesting that ARP may serve as a potential therapeutic target for vascular aging.