Research Paper Volume 9, Issue 2 pp 370—380

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

Gaia Spinetti 1, , Elena Sangalli 1, , Claudia Specchia 1, 2, , Francesco Villa 1, , Chiara Spinelli 1, , Rita Pipolo 3, , Albino Carrizzo 4, , Simona Greco 5, , Christine Voellenkle 5, , Carmine Vecchione 3, 4, , Paolo Madeddu 6, , Fabio Martelli 5, , Annibale Alessandro Puca 1, 3, ,

  • 1 Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy
  • 2 University of Brescia, 25121 Brescia BS, Italy
  • 3 Department of Medicine and Surgery, University of Salerno, 84084 Salerno, Italy
  • 4 Laboratory of Vascular Pathophysiology, IRCCS Neuromed, 86077 Pozzilli (IS), Italy
  • 5 IRCCS Policlinico San Donato, San Donato, Italy
  • 6 University of Bristol, Bristol BS28HW, UK

received: November 22, 2016 ; accepted: January 15, 2017 ; published: January 22, 2017 ;
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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 health-span 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 healthy- versus 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.


CVD: Cardiovascular Disease; GWAS: Genome Wide Association Study; LAV-BPIFB4: Longevity Associated Variant –BPIFB4; LLIs: Long-Living Individuals; MNCs: Mononuclear Cells.