Multigene families, histocompatibility systems, transformation, meiosis, stem cells, and DNA repair

Aging is probably not directly traceable to changes along the whole genome, but to a small portion thereof. The main histocompatibility complex appears to be one among the postulated sets of multigene families responsible. The immortality of transformed cells, the germ line, and possibly certain pluripotential stem cells may suggest common qualitative and/or quantitative differences in DNA repair mechanisms between these cell populations and committed, normal cell populations. A relationship between HLA and at least two diseases showing defective DNA-repair suggests that the same chromosome carrying the main histocompatibility complex may control some repair processes. The correspondence of variation in lifespans in different mouse strains with the DNA repair capabilities and degrees of autoimmune susceptibility of the same strains lends further support to the idea that DNA repair, immune dysfunction and aging in higher animals may be intimately related.