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 of BPIFB4 and ischemia-responding HIF-1ɑ 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-1ɑ/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.
Highlights
The dramatic increase of life expectancy during the 20th century represents one of the greatest achievements of the human society, and creates new challenges to the sustainability of current national health systems [1, 2]
We have recently focused our efforts on Long living individuals (LLIs) and young controls recruited in Cilento, a rural area of southern Italy discovering the association of rs2070325 in BPIFB4 gene to LLI [4, 23]
BPIFB4 is expressed in the CD34+ sub-fraction of circulating mononuclear cells (MNCs), which is acknowledged to participate in vascular repair of ischemic tissues [4]
Summary
The dramatic increase of life expectancy during the 20th century represents one of the greatest achievements of the human society, and creates new challenges to the sustainability of current national health systems [1, 2]. The rising life expectancy within the older population itself is increasing the number and proportion of very old people. Long living individuals (LLIs), that are 90 years of age or older, represent a class of subjects that can provide www.aging‐us.com the scientific community with an invaluable information about key determinants of human life span. While comparison of LLIs versus young controls identifies genes associated with global longevity, the comparison of healthy-LLIs versus non-healthy-LLIs may provide fundamental insights into the mechanistic classifiers of the human health-span, and not aging itself. The potential of the latter approach has not been thoroughly investigated
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