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

Mice that presumably differ just in the major histocompatibility complex (MHC) chromosomal region provide the best evidence that MHC genes affect lifespan. Further evidence is that MHC region genes in some cases are known to influence reproduction, growth, and development. Moreover, MHC genetic associations with disease are well documented. This paper summarizes and defines aspects of the molecular biology, cellular function, and evolution of MHC genes (with special emphasis on the polymorphic MHC class I and II genes) which are important in aging, and attempts to integrate these into an evolutionary genetic perspective of senescence. It is suggested that MHC genes provide a mammalian paradigm for the genetics of lifespan because of their intra- and interspecies diversification, evolutionary selection, and age-specific effects.