The Longevity-Associated BPIFB4 Variant is Anti-Inflammatory
A variant in the gene BPIFB4 has been found to correlate with longevity in humans. In these matters it is worth noting that even small effects on mortality risk result in noticeable correlations with sustained over decades, and indeed all of the known human associations between longevity and genetic variation identified in large study populations are thought to have only modest effect sizes. What are the underlying mechanisms for BPIFB4, however? Researchers here make an argument for suppression of the chronic inflammation of aging as the reason for the association between BPIFB4 and longevity. Certainly chronic inflammatory signaling is disruptive to tissue function, and a major issue in aging.
Increased levels of pro-inflammatory proteins in plasma can be detected in older individuals and associate with the so called chronic low-grade inflammation, which contributes to a faster progression of aged-related cardiovascular (CV) diseases, including frailty, neurodegeneration, gastrointestinal diseases, and disorders reflected by alterations in the composition of gut microbiota. However, successful genetic programme of long-living individuals alters the trajectory of the ageing process, by promoting an efficient immune response that can counterbalance deleterious effects of inflammation and the CV complications. This is the case of BPIFB4 gene in which, homozygosity for a four single-nucleotide polymorphism (SNP) haplotype, the Longevity-Associated Variant (LAV) correlates with prolonged health span and reduced risk of CV complications and inflammation.
The relation between LAV-BPIFB4 and inflammation has been proven in different experimental models, here we hypothesized that also human homozygous carriers of LAV-BPIFB4 gene may experience a lower inflammatory burden as detected by plasma proteomics that could explain their favourable CV risk trajectory over time. We used high-throughput proteomic approach to explore the profiles of circulating proteins from 591 baseline participants selected from the Progressione delle Lesioni Intimali Carotidee (PLIC) cohort according to the BPIFB4 genotype to identify the signatures and differences of BPIFB4 genotypes useful for health and disease management. The observational analysis identified a panel of differentially expressed circulating proteins between the homozygous LAV-BPIFB4 carriers and the other alternative BPIFB4 genotypes highlighting in the latter ones a higher grade of immune-inflammatory markers.