GeroScience · Nov 5, 2026

Claudin-1 as a potential marker of stress-induced premature senescence in vascular smooth muscle cells

By Gadecka A, Janiszewska D, Dudkowska M et al.

Cellular senescence, a permanent state of cell cycle arrest, can result either from external stress and is then called stress-induced premature senescence (SIPS), or from the exhaustion of cell division potential giving rise to replicative senescence (RS). Despite numerous biomarkers, distinguishing SIPS from RS remains challenging. We propose claudin-1 (CLDN1) as a potential cell-specific marker of SIPS in vascular smooth muscle cells (VSMCs). In our study, VSMCs subjected to RS or SIPS exhibited higher levels of CLDN1 mRNA when compared with control cells. ChIP-seq results demonstrated a more open chromatin state, as evidenced by a broader H3K4me3 peak in the gene promoter region, in both SIPS and RS. However, only in SIPS did the broad H3K4me3 peak and increased mRNA level translate into higher protein level, which implies a different regulatory mechanism in RS. Moreover, nuclear accumulation of this protein was also characteristic solely for prematurely senescent cells. Elevated CLDN1 levels were also observed in VSMCs isolated from atherosclerotic plaques, although this was highly donor-dependent. These findings indicate that increased CLDN1 levels in prematurely senescent cells could serve as a promising cell-specific marker of SIPS in VSMCs, both in vitro and ex vivo. We discussed the potential mechanisms that could lead to claudin-1 upregulation and cause the difference observed between SIPS and RS. Identifying new markers specific to different senescence types might be helpful in recognizing conditions that promote accelerated aging and thus the development and progression of age-related diseases. Graphical Abstract

doi.org/10.1007/s11357-026-02634-9 Open access PubMed 42989007 Biomarkers