Skip to main content
PMC home page
Genetics logoLink to Genetics
. 1988 Apr;118(4):693–704. doi: 10.1093/genetics/118.4.693

Murine Chromosomal Regions Correlated with Longevity

R Gelman 1, A Watson 1, R Bronson 1, E Yunis 1
PMCID: PMC1203324  PMID: 3163317

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 < 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), β2M 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). A linear model that regressed mean survival (per strain) on genetic markers found a similar six region model to be best, but replaced Coh by D12Nyu1 on chromosome 12. It should be noted that in both types of regression, there were many other models almost as good as the best one. The total number of chromosomal regions marked by the genotype of the longer lived B parent (out of a possible 141) was not, in general, correlated with survival, although the two shortest lived strains had the most B genes. It appears that BXD recombinant inbred strains can vary widely in survival both within and between strains, that no single genetic marker which has yet been identified can account for much of this variance, (although groups of six or more markers may do so), and that it is not always those strains which inherit the most genes from the long-lived parent B that live longest. The large number of genetic markers found to be significantly correlated with survival raises questions of the reliability of conclusions based on survival studies of only one or two genetic regions.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Baird M. B., Liszczynskyj J. Genetic control of adult lifespan in Drosophila melanogaster. Exp Gerontol. 1985;20(3-4):171–177. doi: 10.1016/0531-5565(85)90034-8. [DOI] [PubMed] [Google Scholar]
  2. Benacerraf B. A hypothesis to relate the specificity of T lymphocytes and the activity of I region-specific Ir genes in macrophages and B lymphocytes. J Immunol. 1978 Jun;120(6):1809–1812. [PubMed] [Google Scholar]
  3. Berek C., Taylor B. A., Eichmann K. Genetics of the idotype of BALB/c myeloma S117: multiple chromosomal loci for Vh genes encoding specificity for group A streptococcal carbohydrate. J Exp Med. 1976 Nov 2;144(5):1164–1174. doi: 10.1084/jem.144.5.1164. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Blatt C., Mileham K., Haas M., Nesbitt M. N., Harper M. E., Simon M. I. Chromosomal mapping of the mink cell focus-inducing and xenotropic env gene family in the mouse. Proc Natl Acad Sci U S A. 1983 Oct;80(20):6298–6302. doi: 10.1073/pnas.80.20.6298. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Clark A. M., Gould A. B. Genetic control of adult life span in Drosophila melanogaster. Exp Gerontol. 1970 Jul;5(2):157–162. doi: 10.1016/0531-5565(70)90004-5. [DOI] [PubMed] [Google Scholar]
  6. Colombatti A., Hughes E. N., Taylor B. A., August J. T. Gene for a major cell surface glycoprotein of mouse macrophages and other phagocytic cells is on chromosome 2. Proc Natl Acad Sci U S A. 1982 Mar;79(6):1926–1929. doi: 10.1073/pnas.79.6.1926. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Elliott R. W., Barlow D., Hogan B. L. Linkage of genes for laminin B1 and B2 subunits on chromosome 1 in mouse. In Vitro Cell Dev Biol. 1985 Aug;21(8):477–484. doi: 10.1007/BF02620837. [DOI] [PubMed] [Google Scholar]
  8. Elliott R. W., Romejko C., Hohman C. Mapping the gene for LTW-4, a 26,000 molecular weight major protein of mouse liver and kidney. Mol Gen Genet. 1980;180(1):17–22. doi: 10.1007/BF00267347. [DOI] [PubMed] [Google Scholar]
  9. Festing M. F., Blackmore D. K. Life span of specified-pathogen-free (MRC category 4) mice and rats. Lab Anim. 1971 Oct;5(2):179–192. doi: 10.1258/002367771781006564. [DOI] [PubMed] [Google Scholar]
  10. Goodrick C. L. Life-span and the inheritance of longevity of inbred mice. J Gerontol. 1975 May;30(3):257–263. doi: 10.1093/geronj/30.3.257. [DOI] [PubMed] [Google Scholar]
  11. Gould A. B., Clark A. M. Behavior of life-shortening genes in genetic mosaics of Drosophila melanogaster. Mech Ageing Dev. 1983 Sep;23(1):1–10. doi: 10.1016/0047-6374(83)90094-5. [DOI] [PubMed] [Google Scholar]
  12. Greenberg L. J., Yunis E. J. Genetic control of autoimmune disease and immune responsiveness and the relationship to aging. Birth Defects Orig Artic Ser. 1978;14(1):249–260. [PubMed] [Google Scholar]
  13. Johnson T. E., Mitchell D. H., Kline S., Kemal R., Foy J. Arresting development arrests aging in the nematode Caenorhabditis elegans. Mech Ageing Dev. 1984 Nov;28(1):23–40. doi: 10.1016/0047-6374(84)90150-7. [DOI] [PubMed] [Google Scholar]
  14. Johnson T. E., Wood W. B. Genetic analysis of life-span in Caenorhabditis elegans. Proc Natl Acad Sci U S A. 1982 Nov;79(21):6603–6607. doi: 10.1073/pnas.79.21.6603. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Klass M. R. A method for the isolation of longevity mutants in the nematode Caenorhabditis elegans and initial results. Mech Ageing Dev. 1983 Jul-Aug;22(3-4):279–286. doi: 10.1016/0047-6374(83)90082-9. [DOI] [PubMed] [Google Scholar]
  16. Luckinbill L. S., Clare M. J. A density threshold for the expression of longevity in Drosophila melanogaster. Heredity (Edinb) 1986 Jun;56(Pt 3):329–335. doi: 10.1038/hdy.1986.54. [DOI] [PubMed] [Google Scholar]
  17. Myers D. D. Review of disease patterns and life span in aging mice: genetic and environmental interactions. Birth Defects Orig Artic Ser. 1978;14(1):41–53. [PubMed] [Google Scholar]
  18. Pelkonen J., Karjalainen K., Mäkelä O., Taylor B. A. Map position of Igh-Oxa gene within the Igh region of the DBA/2 mouse strain. J Immunol. 1982 Jul;129(1):242–244. [PubMed] [Google Scholar]
  19. Popp D. M. Use of congenic mice to study the genetic basis of degenerative disease. Birth Defects Orig Artic Ser. 1978;14(1):261–279. [PubMed] [Google Scholar]
  20. Schnebel E. M., Grossfield J. A comparison of life span characteristics in Drosophila. Exp Gerontol. 1983;18(5):325–337. doi: 10.1016/0531-5565(83)90011-6. [DOI] [PubMed] [Google Scholar]
  21. Simmons D. L., Kasper C. B. Genetic polymorphisms for a phenobarbital-inducible cytochrome P-450 map to the Coh locus in mice. J Biol Chem. 1983 Aug 25;258(16):9585–9588. [PubMed] [Google Scholar]
  22. Smith G. S., Walford R. L. Influence of the main histocompatibility complex on ageing in mice. Nature. 1977 Dec 22;270(5639):727–729. doi: 10.1038/270727a0. [DOI] [PubMed] [Google Scholar]
  23. Smith G. S., Walford R. L., Mickey M. R. Lifespan and incidence of cancer and other diseases in selected long-lived inbred mice and their F 1 hybrids. J Natl Cancer Inst. 1973 May;50(5):1195–1213. doi: 10.1093/jnci/50.5.1195. [DOI] [PubMed] [Google Scholar]
  24. Storer J. B. Effect of aging and radiation in mice of different genotypes. Birth Defects Orig Artic Ser. 1978;14(1):55–70. [PubMed] [Google Scholar]
  25. Storer J. B. Longevity and gross pathology at death in 22 inbred mouse strains. J Gerontol. 1966 Jul;21(3):404–409. doi: 10.1093/geronj/21.3.404. [DOI] [PubMed] [Google Scholar]
  26. Tada N., Kimura S., Hatzfeld A., Hämmerling U. Ly-m11: the H-3 region of mouse chromosome 2 controls a new surface alloantigen. Immunogenetics. 1980;11(5):441–449. doi: 10.1007/BF01567813. [DOI] [PubMed] [Google Scholar]
  27. Wood A. W., Taylor B. A. Genetic regulation of coumarin hydroxylase activity in mice. Evidence for single locus control on chromosome. J Biol Chem. 1979 Jul 10;254(13):5647–5651. [PubMed] [Google Scholar]
  28. Yunis E. J., Greenberg L. J. Immunopathology of aging. Hum Pathol. 1974 Mar;5(2):122–125. doi: 10.1016/s0046-8177(74)80058-4. [DOI] [PubMed] [Google Scholar]
  29. Yunis E. J., Watson A. L., Gelman R. S., Sylvia S. J., Bronson R., Dorf M. E. Traits that influence longevity in mice. Genetics. 1984 Dec;108(4):999–1011. doi: 10.1093/genetics/108.4.999. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES