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  11. Longevity-associated Bpifb4 Gene Counteracts The Inflammatory Signaling

Longevity-associated BPIFB4 gene counteracts the inflammatory signaling

Monica Cattaneo1, Andrea Baragetti1,2, Alberto Malovini3

  • 1Cardiovascular Department, IRCCS MultiMedica, Milan, Italy.

Immunity & Ageing : I & A
|March 12, 2024

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View abstract on PubMed

Summary
This summary is machine-generated.

Homozygosity for the Longevity-Associated Variant (LAV) of the BPIFB4 gene reduces inflammation in humans and IBD models. This finding suggests LAV-BPIFB4 may offer therapeutic benefits for inflammatory disorders.

Area of Science:

  • Genetics and Aging Research
  • Immunology and Inflammation
  • Proteomics and Biomarker Discovery

Background:

  • Chronic low-grade inflammation in aging is linked to cardiovascular diseases and frailty.
  • The BPIFB4 gene, specifically the Longevity-Associated Variant (LAV) haplotype, is associated with extended health span and reduced cardiovascular risk.
  • This study investigates the anti-inflammatory effects of homozygous LAV-BPIFB4 in humans and its therapeutic potential.

Purpose of the Study:

  • To investigate the association between homozygous LAV-BPIFB4 genotype and plasma inflammatory markers.
  • To explore the therapeutic effects of LAV-BPIFB4 in models of intestinal inflammation.
  • To understand the role of BPIFB4 in modulating the aging process and associated inflammatory burden.

Main Methods:

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  • High-throughput proteomic analysis of plasma from 591 participants stratified by BPIFB4 genotype.
  • Observational analysis to identify differentially expressed proteins between homozygous LAV-BPIFB4 carriers and other genotypes.
  • In vitro studies using intestinal epithelial organoids and monolayer models from IBD patients to assess LAV-BPIFB4 treatment effects.

    • Main Results:

    • Proteomic analysis revealed lower levels of immune-inflammatory markers in homozygous LAV-BPIFB4 carriers compared to other genotypes.
    • In vitro studies demonstrated beneficial effects of LAV-BPIFB4 treatment on intestinal barrier models and IBD patient-derived organoids.
    • These findings suggest a protective role of homozygous LAV-BPIFB4 against inflammation.

    Conclusions:

    • Homozygosity for LAV-BPIFB4 is associated with reduced systemic inflammation in a human cohort.
    • LAV-BPIFB4 exhibits therapeutic potential in mitigating inflammation in inflammatory bowel disease (IBD) models.
    • Further independent studies are warranted to confirm these preliminary findings and characterize the therapeutic applications of LAV-BPIFB4.