Human Leukocyte Antigen (HLA) part 119

HLA AND LONGEVITY

Literature data suggest that human longevity may be directly correlated with optimal functioning of the immune system. Therefore, it is likely that one of the genetic determinants  of longevity resides in those polymorphysms for the immune system genes that regulate immune response. Accordingly, studies performed  on mice have suggested that the HLA, known to control  a variety of immune functions, is associated with the lifespan of the strains. In the last 25 years, a fair number of cross-sectional studies that searched for the role of HLA genes on human longevity by comparing HLA antigen frequencies between groups of young and  elderly persons have been published, but conflicting findings have been obtained. In fact, the same HLA antigens are increased in some studies decreased or unchanged in others. On the whole that could lead to hypothesize that the observed age-related differences in the frequency of HLA antigens are due to bias. The hypothesisis real for most studies owing to major methodological problems. However, some studies that do not meet these biases have shown an  association between longevity and some HLA-DR alleles or HLA-B8, DR3 haplotype, known to be involved  in the antigen non-specific control of immune response. Thus, HLA studies in human may be interpreted to support suggestions derived from the studies  on congenic mice on HLA effects on longevity. However, in mice, the association may be by way of susceptibility to lymphomas whereas, in human beings, the effect on longevity is likely, via infectious disease susceptibility. Longevity is associated with positive or negative selection of alleles  (or haplotypes) that, respectively, confer resistance or susceptibility to diseases, via peptide presentation or via antigen non-specific control of the immune response.