A Model of Evolutionary Selection: The Cardiovascular Protective Function of the Longevity Associated Variant of BPIFB4

Int J Mol Sci. 2018 Oct 19;19(10):3229. doi: 10.3390/ijms19103229.


Evolutionary forces select genetic variants that allow adaptation to environmental stresses. The genomes of centenarian populations could recapitulate the evolutionary adaptation model and reveal the secrets of disease resistance shown by these individuals. Indeed, longevity phenotype is supposed to have a genetic background able to survive or escape to age-related diseases. Among these, cardiovascular diseases (CVDs) are the most lethal and their major risk factor is aging and the associated frailty status. One example of genetic evolution revealed by the study of centenarians genome is the four missense Single Nucleotide Polymorphisms (SNPs) haplotype in bactericidal/permeability-increasing fold-containing family B, member 4 (BPIFB4) locus that is enriched in long living individuals: the longevity associated variant (LAV). Indeed, LAV-BPIFB4 is able to improve endothelial function and revascularization through the increase of endothelial nitric oxide synthase (eNOS) dependent nitric oxide production. This review recapitulates the beneficial effects of LAV-BPIFB4 and its therapeutic potential for the treatment of CVDs.

Keywords: BPIFB4; aging; angiogenesis; cardiovascular disease; eNOS.

Publication types

  • Review

MeSH terms

  • Cardiovascular Diseases / genetics*
  • Evolution, Molecular
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Longevity / genetics*
  • Phosphoproteins / genetics*
  • Polymorphism, Single Nucleotide*
  • Selection, Genetic*


  • BPIFB4 protein, human
  • Intercellular Signaling Peptides and Proteins
  • Phosphoproteins