Immunogenetics of longevity. Is major histocompatibility complex polymorphism relevant to the control of human longevity? A review of literature data

Literature data suggest that human longevity may be directly correlated wit h optimal functioning of the immune system. Therefore, it is likely that on e of the genetic determinants of longevity resides in those polymorphisms f or the immune system genes that regulate immune responses. Accordingly, stu dies performed on mice have suggested that the Major Histocompatibility Com plex (MHC). known to control a variety of immune functions, is associated w ith the life span of the strains. In the last 25 years, a fair number of cr oss-sectional studies that searched fur the role of HLA (the human MHC) gen es on human longevity by comparing HLA antigen frequencies between groups o f young and elderly persons have been published, but conflicting findings h ave been obtained. In fact. the same HLA antigens are increased in some stu dies. decreased in others and unchanged in others. On the whole, that could lead us to hypothesize that the observed age-related differences in the fr equency of HLA antigens are due to bias. In our opinion, this hypothesis is real for most studies owing to major methodological problems. However. som e studies that do not meet these biases have shown an association between l ongevity and some HLA-DR alleles or HLA-B8.DR2 haplotype. known to be invol ved in the antigen non-specific control of immune response. Thus. HLA studi es in man may be interpreted to support suggestions derived from the studie s on congenic mice on MHC effects on longevity. However, in mice the associ ation 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 disea se(s), via peptide presentation or via antigen non-specific control of the immune response. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved .