The HLA-B*57:01 Haplotype, Genetic Key Linking Innate Immunity and Longevity

In our recent research on AIDS Elite controllers, we demonstrated that the HLA-B*57:01 allele is part of an extensive MHC haplotype associated with impaired MICA/MICB function. Considering the pivotal role of natural killer (NK) cells and innate immunity in fighting cancer and infectious diseases, we investigated whether this allele could also influence human longevity. To this end, we performed a multinational European study including 2,597 centenarians and 9,973 controls. We found that HLA-B*57:01 was consistently less frequent in the European centenarian cohorts compared with the corresponding controls (OR ≈ 0.68, p &;lt 0.0005). These findings provide the first in vivo genetic evidence that innate immunity and NK cell function are key components of human longevity.

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Publication Details

Journal
Aging and Disease
Published
2025-01-01
DOI
https://doi.org/10.14336/ad.2025.1109
Primary Topic
Atherosclerosis and Cardiovascular Diseases
Type
article
Field-Weighted Citation Impact
0.00

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article

The HLA-B*57:01 Haplotype, Genetic Key Linking Innate Immunity and Longevity

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Aging and Disease
Atherosclerosis and Cardiovascular Diseases
article

The HLA-B*57:01 Haplotype, Genetic Key Linking Innate Immunity and Longevity

Paolo Garagnani, Sigrid Le Clerc, Kaare Christensen, Alexandre How‐Kit, Myriam Rahmouni, Nicolás Mendoza-Mejía, Armand Bensussan, Marianne Nygaard, Almut Nebel, Cristina Giuliani, Raissa Medina‐Santos, Mirko Manetti, Daniela Colucci, Maxime Tison, Jean‐François Deleuze, Taoufik Labib, Jean-Louis Spadoni, Jean‐François Zagury, Samuel Hiet, Marco Lamanda
article en

Abstract

In our recent research on AIDS Elite controllers, we demonstrated that the HLA-B*57:01 allele is part of an extensive MHC haplotype associated with impaired MICA/MICB function. Considering the pivotal role of natural killer (NK) cells and innate immunity in fighting cancer and infectious diseases, we investigated whether this allele could also influence human longevity. To this end, we performed a multinational European study including 2,597 centenarians and 9,973 controls. We found that HLA-B*57:01 was consistently less frequent in the European centenarian cohorts compared with the corresponding controls (OR ≈ 0.68, p &;lt 0.0005). These findings provide the first in vivo genetic evidence that innate immunity and NK cell function are key components of human longevity.

Aging and Disease
Conservatoire National des Arts et Métiers (FR), Inserm (FR), University of Southern Denmark (DK), Odense University Hospital (DK), Fondation Jean Dausset-CEPH (FR), Christian-Albrechts-Universität zu Kiel (DE), Génomique Bioinformatique et Applications (FR), Azienda USL di Bologna (IT), Hôpital Saint-Louis (FR), University of Bologna (IT)
European Commission
Openalex Percentile: Top 68%
Atherosclerosis and Cardiovascular Diseases
DOIOpen Access PDFOpenAlex
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