Genetics of life span in mice.
Thymic involution that occurs earlier in some individuals than others may be the result of complex interactions between genetic factors and the environment. Such interactions may produce defects of thymus-dependent immune regulation associated with susceptibility to developing autoimmune diseases, malignancy, and an increased number of infections associated with aging. The major histocompatibility complex may be important in determining profiles of cause of death and length of life in mice. Genetic influences on life span involve interactions between loci and allelic interactions during life which may change following viral infections or exposure to other environmental factors. We have used different experimental protocols to study the influence of H-2 on life span and found that interactions between genetic regions, are inconsistent, particularly when comparing mice infected or not infected with Sendai virus. Genes important for life span need to be studied against many genetic backgrounds and under differing environmental conditions because of the complexity of the genetics of life span. Several genetic models were used to demonstrate that the MHC is a marker of life span in backcross and intercross male mice of the H-2d and H-2b genotypes in B10 congenic mice. Females lived longer than males in backcross and intercross mice, while males lived longer than females in B10 congenics. H-2d was at a disadvantage for life span in backcross mice of the dilute brown and brown males exposed to Sendai infection, but intercross mice not exposed to Sendai virus of the same genotype were not at a disadvantage. H-2d mice were not disadvantaged when compared to H-2b in B10 congenics that had not been exposed to Sendai virus infection but the reverse was true when they were exposed. Overall, all our studies suggest that genetic influences in life span may involve interactions between loci and many allelic interactions in growing animals or humans. These genetic influences on life span may vary after they are exposed to infections or other environmental conditions. This paper emphasizes the need to use several genetic models, especially animals that have been monitored for infections, to study the genetics of life span.
Yunis
E J
EJ
Dana Farber Cancer Institute, Boston, MA 02115.
Salazar
M
M
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D008136:Longevity / Q000235:genetics*; D008285:Major Histocompatibility Complex; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains / Q000235:genetics*; D008957:Models, Genetic; D010222:Parainfluenza Virus 1, Human / Q000276:immunology; D018184:Paramyxoviridae Infections / Q000276:immunology; D011995:Recombination, Genetic