The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy

Gaia Spinetti, Elena Sangalli, Claudia Specchia, Francesco Villa, Chiara Spinelli, Rita Pipolo, Albino Carrizzo, Simona Greco, Christine Voellenkle, Carmine Vecchione, Paolo Madeddu, Fabio Martelli, Annibale Alessandro Puca*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

25 Citations (Scopus)
297 Downloads (Pure)


The study of the health status in long-living individuals (LLIs) may help identifying health-span and life-span determinants. BPI-Fold-Containing-Family-B-Member-4 (BPIFB4) protein is higher in healthy vs. non-healthy (frail) LLIs serum and its longevity-associated variant forced expression improves cardiovascular outcomes in ischemia mice models. Thus, we tested the association of BPIFB4 and ischemia-responding HIF-1α pathway components (i.e. CXCR4, AK3, ALDO-C, ADM, VEGF-A, GLUT-1 and miR-210) with human life-span and healthspan by analyzing mRNA expression in circulating mononuclear cells (MNCs) of LLIs (N=14 healthy; N=31 frail) and young controls (N=63). ALDO-C, ADM, VEGF-A and GLUT-1 significantly decreased and miR-210 increased in LLIs vs. controls. Only VEGF-A and GLUT-1 showed further significant reduction in healthy-LLIs vs. frail-LLIs comparison. While BPIFB4 and CXCR4 were similar between LLIs and controls, BPIFB4 was significantly higher and CXCR4 lower in healthyversus frail-LLIs. On a new set of LLIs (N=7 healthy and N=5 non-healthy) we assessed a potentially correlated function with low CXCR4 expression. Healthy donors' MNCs showed efficient migration ability toward CXCR4 ligand SDF-1α/CXCL12 and high percentage of migrated CXCR4pos cells which inversely correlated with CXCR4 RNA expression. In conclusion, BPIFB4 and CXCR4 expression classify LLIs health status that correlates with maintained MNCs migration.

Original languageEnglish
Pages (from-to)370-380
Number of pages11
Issue number2
Publication statusPublished - 22 Jan 2017


  • BPIFB4
  • CXCR4
  • HIF-1α targets
  • Long-living individuals
  • Mononuclear cell migration


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