Genetic variability and rodent models of human aging.

Inbred strains, outbred strains, and natural populations of rodents differ greatly in the amount and nature of the genetic variability they possess. Consequently, as models of human aging they vary with respect to the areas of research to which they are best suited. Inbred strains, in which all individuals are genetically identical, are best suited as models of specific disease processes and for manipulations involving tissue transplantation. Their lack of genetic variability, however, and the disruption of genetic linkage groups that occurs during inbreeding limit their value as models of more general aging processes. Outbred strains exhibit large interindividual genetic variation--a result of ongoing random accumulation of deleterious alleles with late ages of action. This makes them ideal models for studying the diversity of pathologic lesions, connections between pathologies, and susceptibility to pathologic lesions that collectively produce the reductions in reproductive capacity, physiological efficiency, and viability that are characteristic of aging. Natural populations also may exhibit relatively large amounts of interindividual genetic variability. However, difficulties with husbandry, variable parasite loads, and complex population genetics can compromise their suitability as models of human aging. Ultimately, a consideration of the range of animal models available and a more careful matching of the goals of a study with the genetic system of the model will prove fruitful to gerontology.