title: The expression of the BPIFB4 and CXCR4 associates with sustained health in long-living individuals from Cilento-Italy.
abstract: 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 ofBPIFB4and ischemia-responding HIF-1α pathway components (i.e.CXCR4,AK3, ALDO-C, ADM,VEGF-A,GLUT-1and 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-AandGLUT-1significantly decreased and miR-210 increased in LLIs vs.
  
  
  
  OnlyVEGF-AandGLUT-1showed further significant reduction in healthy-LLIs vs. frail-LLIs comparison. WhileBPIFB4andCXCR4were similar between LLIs and controls,BPIFB4was significantly higher andCXCR4lower 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 CXCR4poscells which inversely correlated with CXCR4 RNA expression. In conclusion, BPIFB4 and CXCR4 expression classify LLIs health status that correlates with maintained MNCs migration.
authors.affiliation: Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Spinetti
authors.affiliation: Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy.
authors.forename: Elena
authors.initials: E
authors.lastname: Sangalli
authors.affiliation: Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy.|University of Brescia, 25121 Brescia BS, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Specchia
authors.affiliation: Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Villa
authors.affiliation: Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Spinelli
authors.affiliation: Department of Medicine and Surgery, University of Salerno, 84084 Salerno, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Pipolo
authors.affiliation: Laboratory of Vascular Pathophysiology, IRCCS Neuromed, 86077 Pozzilli (IS), Italy.
authors.forename: Albino
authors.initials: A
authors.lastname: Carrizzo
authors.affiliation: IRCCS Policlinico San Donato, San Donato, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Greco
authors.affiliation: IRCCS Policlinico San Donato, San Donato, Italy.
authors.forename: Christine
authors.initials: C
authors.lastname: Voellenkle
authors.affiliation: Department of Medicine and Surgery, University of Salerno, 84084 Salerno, Italy.|Laboratory of Vascular Pathophysiology, IRCCS Neuromed, 86077 Pozzilli (IS), Italy.
authors.forename: Carmine
authors.initials: C
authors.lastname: Vecchione
authors.affiliation: University of Bristol, Bristol BS28HW, UK.
authors.forename: Paolo
authors.initials: P
authors.lastname: Madeddu
authors.affiliation: IRCCS Policlinico San Donato, San Donato, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Martelli
authors.affiliation: Cardiovascular Research Unit, IRCCS MultiMedica, 20138 Milan, Italy.|Department of Medicine and Surgery, University of Salerno, 84084 Salerno, Italy.
authors.forename: Annibale Alessandro
authors.initials: AA
authors.lastname: Puca
mesh_terms: D053607:Adrenomedullin / Q000235:genetics; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D002465:Cell Movement / Q000502:physiology; D005260:Female; D051272:Glucose Transporter Type 1 / Q000235:genetics; D006304:Health Status; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000166:cytology / Q000378:metabolism; D008136:Longevity / Q000235:genetics*; D008297:Male; D010750:Phosphoproteins / Q000235:genetics*; D019718:Receptors, CXCR4 / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics
chemical_list: C507862:ADM protein, human; C000602462:BPIFB4 protein, human; C527276:CXCR4 protein, human; D051272:Glucose Transporter Type 1; D036341:Intercellular Signaling Peptides and Proteins; D010750:Phosphoproteins; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D053607:Adrenomedullin
keywords: BPIFB4; CXCR4; HIF-1α targets; long-living individuals; mononuclear cell migration