GENES OF THE MAJOR HISTOCOMPATIBILITY COMPLEX AND THE EVOLUTIONARY GENETICS OF LIFE-SPAN

Mice that presumably differ just in the major histocompatibility compl ex (MHC) chromosomal region provide the best evidence that MHC genes a ffect lifespan. Further evidence is that MHC region genes in some case s are known to influence reproduction, growth, and development. Moreov er, MHC genetic associations with disease are well documented. This pa per summarizes and defines aspects of the molecular biology, cellular function, and evolution of MHC genes (with special emphasis on the pol ymorphic MHC class I and II genes) which are important in aging, and a ttempts to integrate these into an evolutionary genetic perspective of senescence. It is suggested that MHC genes provide a mammalian paradi gm for the genetics of lifespan because of their intra- and interspeci es diversification, evolutionary selection, and age-specific effects.