Human Longevity and Immunogenetic Architecture: A Biogerontological Perspective<b></b>, Довголіття людини та імуногенетична архітектура: біогеронтологічна перспектива

<jats:p>Human longevity is a complex, polygenic, and multilayered phenotype that cannot be adequately explained by individual genetic variants. This review examines the immunogenetic architecture of human longevity from a biogerontological perspective, with particular emphasis on human leukocyte antigen (HLA) variation, single nucleotide polymorphisms (SNPs), and their interactions with biological pathways involved in aging. Genome-wide association studies (GWAS), SNP genotyping, and high-resolution HLA sequencing have enabled the identification of numerous genetic variants associated with lifespan; however, the biological and causal interpretation of these associations remains challenging. The high polymorphism and extensive linkage disequilibrium of the HLA region, small genetic effect sizes, population heterogeneity, and gene–environment interactions represent major limitations to the generalizability of current findings. Emerging evidence indicates that longevity should be understood not merely in terms of specific alleles, but as a dynamic biological network shaped by interactions among immune regulation, inflammatory balance, metabolic adaptation, and cellular stress responses. Accordingly, the effects of HLA and other immunogenetic variants should be interpreted in the context of population-level survival selection and environmental exposures accumulated across the life course.</jats:p>