Aging cellJun 25, 2026

A New Role for LAV-BPIFB4 and Platelet CD47 in Supporting Immune Strength for Long Life

Longevity & Aging Weekly Brief ↗PubMed ↗DOI ↗OA ↗

Updated Jun 27, 2026

Abstract

Centenarians exhibit elevated levels of on circulating platelets, suggesting enhanced immune functions.

Long-living individuals possess genetic variants that may confer immune resilience and resistance to age-related diseases.
The longevity-associated variant of BPIFB4 is linked to reduced inflammation and cardiovascular protection.
Elevated CD47 levels on platelets are associated with improved immunomodulatory capacity in centenarians and carriers.
Platelets from carriers of the longevity variant may suppress inflammatory responses through CD47-dependent mechanisms.
Administration of recombinant LAV-BPIFB4 increased CD47 levels on mouse platelets and reduced inflammatory activation in response to stimuli.
These findings highlight the potential of LAV-BPIFB4 as a therapeutic strategy for improving health in aging populations.

Simplified

Long-living individuals (LLIs) possess remarkable genetic resilience, characterized by protective variants that confer immune robustness and resistance to age-related diseases. The longevity-associated variant of BPIFB4 (), enriched in centenarians, demonstrated pleiotropic benefits including reduced inflammation, cardiovascular protection, and immune system rejuvenation. However, the molecular mechanisms underlying these protective effects remain incompletely understood. Here, we revealed that LAV-BPIFB4 fundamentally reshaped the immune features of platelets to establish enhanced immunomodulatory capacity through upregulation. Of note, centenarians displayed an elevated percentage of circulating CD47⁺ reticulated platelets (RPs), a condition mimicked by LAV-BPIFB4 carriers which exhibited significantly elevated CD47 levels both on RPs and mature platelets' surface. In agreement with an early acquirement of CD47 overexpression, MEG-01 megakaryoblastic cells overexpressing LAV-BPIFB4 produced CD47-high platelet-sized particles. Functionally, platelets from LAV carriers suppressed monocyte activation and inflammatory cytokine production through CD47-dependent mechanisms, selectively reducing p38 MAPK activation while leaving NF-κB signaling largely unaffected in response to LPS. rhLAV-BPIFB4 administration in vivo increased CD47 on murine platelets and reduced, ex vivo, LPS-induced monocyte activation, validating cross-species therapeutic potential. Critically, rhLAV-BPIFB4 protein phenocopies genetic effects, rapidly increasing CD47 expression on wild-type platelets through cytoskeleton-dependent trafficking mechanisms and conferring enhanced anti-inflammatory capacity. This might represent a translatable strategy to replicate some of the biological features associated with a longevity-associated variant beyond genetic carriers. Our findings establish the platelet-CD47-monocyte axis as a pivotal pathway for healthy aging and reveal recombinant LAV-BPIFB4 as a promising therapeutic approach for managing inflammaging and cardiovascular disease by harnessing the immune-tuning capacity characteristic of exceptional longevity.

Full Text

What this is

Long-living individuals (LLIs) exhibit genetic resilience linked to immune robustness and reduced age-related diseases.
The longevity-associated variant of BPIFB4 () enhances immune features through upregulation.
This study explores the mechanisms by which influences platelet function and immune modulation.

Essence

enhances immune resilience by upregulating on platelets, improving their immunomodulatory capacity.

Key takeaways

reshapes platelet immune features, leading to increased levels. This change enhances the platelets' ability to modulate immune responses.
Centenarians show a higher percentage of circulating -reticulated platelets, indicating a potential link between levels and longevity.
Recombinant administration in vivo boosts levels on murine platelets, suggesting therapeutic potential for managing inflammation and cardiovascular diseases.

Caveats

The study primarily focuses on genetic associations and mechanisms, which may not fully translate to clinical outcomes in broader populations.
Further research is needed to confirm the therapeutic efficacy of rhLAV-BPIFB4 in humans.

Definitions

LAV-BPIFB4: A longevity-associated variant of the BPIFB4 gene linked to immune resilience in long-living individuals.
CD47: A protein that plays a role in immune regulation and is upregulated by LAV-BPIFB4 in platelets.

Simplified

Author Contributions

E.C. designed and coordinated the research team and wrote the brief report. V.L., F.M., R.M.E., and R.L., conducted ex vivo experiments and FACS analysis. A.D. and A.C. were involved in animal model. C.B. and A.M. established MEG‐01 cell lines and performed ELISA assays. G.R., F.D.P., and A.F. cared for the subjects of the study and evaluation of their health status. C.V. contributed to the critical discussion. A.A.P. supervised and revised the project in its entirety and provided financial support. All authors approved the final version to be published.

Funding

This work was supported by University of Salerno funding (Codice ORSA254275; PI: Elena Ciaglia); furthermore A.A.P. was supported by the MUR FIS‐2024‐03953 Advanced Grant (Fondo Italiano per la Scienza—3rd Edition) and by the Italian Ministry of Health Ricerca Corrente to the IRCCS MultiMedica.

Ethics Statement

All animal study were performed according to approved protocols by the Istituto Superiore di Sanità, Rome (766/2018‐PR) and were conducted according to EU Directive 2010/63/EU on animals used for scientific purposes. The collection of human samples was approved by the Ethics Committee of Campania 2 for the project “T.V.B. Tromboembolismo venoso e BPIFB4: correlazione tra i livelli di espressione di BPIFB4 e il rischio cardiovascolare in pazienti naïve” (prot. ASLSA‐0281308‐2024 del 23‐12‐2024) and by the IRCCS MultiMedica ethical committee.

Conflicts of Interest

The authors declare no conflicts of interest.

Supporting information

Funding

Competing interests

The authors declare no conflicts of interest.

PubMed

A New Role for LAV-BPIFB4 and Platelet CD47 in Supporting Immune Strength for Long Life

Abstract

Full Text

What this is

Essence

Key takeaways

Caveats

Definitions

Author Contributions

Funding

Ethics Statement

Conflicts of Interest

Supporting information

Funding

Competing interests

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Abstract

Full Text

What this is

Essence

Key takeaways

Caveats

Definitions

Author Contributions

Funding

Ethics Statement

Conflicts of Interest

Supporting information

Funding

Competing interests

Related papers

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