Pannexin 1 expression in circulating progenitor marker-positive cells is associated with senescence and...

Upregulation of Pannexin 1 (Panx1) has been reported in senescent human endothelial colony-forming cells. We examined whether Panx1 served as a potential biomarker of senescence in peripheral blood mononuclear cells (PBMCs) expressing progenitor markers and its association with inflammation, nitric oxide (NO), and cardiovascular risk.

Panx1 transcripts were assessed in PBMCs from 60 non-diabetic donors (20 aged 20-30 years and 40 aged ≥ 65 years). ECFCs were examined for Panx1-NO interaction. A separate flow-cytometry cohort comprised 50 donors (25 young and 25 elderly) targeting CD34⁺CD45^- PBMCs and CD133⁺CD45^- PBMCs expressing kinase insert domain receptor (KDR), Panx1, senescence-associated beta-galactosidase (SA-β-gal), and NO. Plasma tumor necrosis factor-α and interleukin-6 were detected. Framingham Risk Score (FRS) analyses were confined to elderly participants. Correlation, partial-correlation, multivariable, ROC/AUC and incremental-value analyses were performed with false-discovery-rate and bootstrap procedures as appropriate.

Higher Panx1 transcript levels existed in PBMCs of the elderly versus young donors. Among the elderly, higher Panx1 transcript levels existed in those respectively with increased fasting glucose (> 100 versus 100 mg/dL) and moderate-to-high FRS (versus low FRS). Panx1 interacted with NO in ECFCs. The proportion of CD34⁺CD45^- cells in PBMCs was lower, whereas that of CD133⁺CD45^- cells was higher, in the elderly versus young donors. At individual cell level, the number of Panx1⁺ cells per 1 × 10⁴ cells increased, whereas the number of NO-related fluorescence-positive cells decreased, in the elderly versus young donors. Panx1 correlated with SA-β-gal in CD34⁺KDR⁺CD45^- progenitor populations after adjustment for age, sex, body mass index and fasting glucose, whereas associations in other populations were attenuated by age. No robust independent association existed between Panx1 and NO. Pooled Panx1-cytokine correlations were largely explained by age-group separation. In elderly participants, Panx1 in CD34⁺ CD45^- cells was associated with FRS (Spearman r_s=0.455, nominal p = 0.022; FDR p = 0.334) and discriminated FRS ≥ 10% (AUC 0.767, 95% CI 0.560-0.937), but incremental value over conventional clinical factors was inconsistently established.

Panx1 in selected circulating progenitor-cell populations is associated with cellular senescence and cardiovascular risk in non-diabetic elderly individuals. Panx1 as a candidate cellular senescence-associated biomarker requires prospective validation.