Murine chromosomal regions correlated with longevity.

Abstract

Abstract In this longevity analysis of 360 BXD recombinant inbred female mice (20 different strains), 2 strains had very significantly shorter survival and 1 strain had very significantly longer survival than the other 17 strains; 4 other strains had less significant lengthening of survival compared to the other 13 strains in a proportional hazards model of survival. Mean survival on the shortest lived strain was 479 days; on the longest lived strain the mean survival was almost double (904 days). Ranges of survival within strain were very large (averaging 642 days), and strain accounted for only 29% of the variation in survival, showing that there are important environmental and/or special developmental effects on longevity even in this colony housed in a single room. Each strain had been typed for markers of 141 regions on 15 chromosomes; 101 of these markers had distinguishable distributions on the 20 strains. The two shortest lived strains had the same alleles for 63% of the markers. The single region most significantly correlated with survival (marked by P450, Coh, Xmmv-35 on chromosome 7) divided the mice into two groups with survival medians which differed by 153 days (755 days for mice with a B genotype; 602 days for mice with a D genotype). Evaluated individually, 44% of the genetic markers (including some markers on 11 of 15 chromosomes with any markers typed) were found to be significantly correlated with survival (P less than 0.05) although one would only expect 5% of the markers to be significant by chance. While studies of many markers should adjust for the multiple comparisons problem, one interpretation of these crude P values is that any experiment with only one of these "significant" markers typed would be likely to conclude that the marker was a significant predictor of survival. Two types of multiple regression models were used to examine the correlation with survival of groups of genes. When a proportional hazards model for survival was done in terms of genotype regions, a six genetic region model best correlated with survival: that marked by P450, Coh, Xmmv-35 on chromosome 7 (B allele lives longer), Ly-24 on chromosome 2 (B allele lives longer), beta 2M and H-3 on chromosome 2 (D allele lives longer) Lamb-2 on chromosome 1 (D allele lives longer), Ltw-4 on chromosome 1 (B allele lives longer), and the Igh area of chromosome 12 (Igh-Sa4, Igh-Sa2, Igh-Bgl, Igh-Nbp, Igh-Npid, Igh-Gte, Odc-8, and Ox-1; D allele lives longer).(ABSTRACT TRUNCATED AT 400 WORDS)