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RESEARCH PRODUCT

Major Histocompatibility Complex Polymorphisms and Ageing.

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ASTRACT Longevity seems to be directly correlated with optimal functioning of the immune system, suggesting that some genetic determinants of longevity might reside in those polymorphisms for the immune system genes that regulate immune responses. Accordingly, mouse lifespan is influenced by MHC (major histocompatibility complex) genotype. The HLA (the human MHC) region encompasses over 4 Mb of DNA on the chromosome band 6p21.3 and its extensive characterisation has recently culminated in the determination of the nucleotide sequence of the entire region, confirming the presence of ~ 220 genes. The MHC is traditionally divided into the class I, class II and class III regions. Most HLA genes involved in the immune response fall into classes I and II, which encode highly polymorphic heterodimeric glycoproteins involved in graft rejection and antigen presentation to T cells. However, many genes of the class III region are also involved in the immune and inflammatory responses.. MHC polymorphisms have been the focus of a vast number of ageing association studies. One of the limitations in the most reported studies is the number of aged individuals available of both genders, and the lack of complete background histories of health or ethnicity for study participants. However, also taking into account well planned and designed studies, discordant results have been obtained. The discordant results of MHC/ageing association studies might be due to distinct linkage in different cohorts or to other interacting, genetic or environmental factors or to the heterogeneity of ageing. Nevertheless, bearing all the reported studies in mind, there is no convincing evidence of a strong, direct association between longevity and any MHC alleles.