LONGEVITY ASSOCIATED VARIANT OF BPIFB4 TUNES THE MACROPHAGES POLARIZATION AND MITIGATE MONOCYTE MEDIATED ACQUIRED IMMUNE RESPONSE: A POSSIBLE EXPLANATION OF HOW CENTENARIANS ESCAPE AGING DISEASES

Abstract

Reaching exceptional longevity is a consequence of aging delay driven by genetic and epigenetic factors,which are either inherited or acquired. It has been postulated that aging is driven by imbalance betweeninflammatory and anti-inflammatory networks that results in the low grade chronic pro-inflammatorystatus causing most of the physiopathological changes triggered by aging. In this respect, the activation ofmonocyte-macrophages plays a major roles in finely tune the immune responses as they cover a continuumof functional states which oscillate from a patrolling protective effect toward an inflammatory ones. Wepreviously identified a four-SNPs haplotype, the Longevity-associated variant (LAV) of bactericidal/permeabilityincreasing fold-containing-family-B-member-4 (BPIFB4) able to activate calcium, PKC-a,eNOS, rescuing endothelial dysfunction in aged mice and inducing revascularization through homing ofprogenitor cells. BPIFB4 abundance in serum of healthy centenarians as compared to non-healthy ones,the therapeutic potentials LAV-BPIFB4 in improving vascular homeostasis, at least in part mediated byLy6Chigh monocytes, and BPIFB4 expression in bone marrow myeloid cells induced us to evaluate ifLAV-BPIFB4 may improve immune regulation.