Journals of Gerontology Series A: Biological Sciences and Medical Sciences, Vol 53, Issue 4 M257-M263, Copyright © 1998 by The Gerontological Society of America

JOURNAL ARTICLE

Marker loci associated with life span in genetically heterogeneous mice

RA Miller, C Chrisp, AU Jackson and D Burke
Department of Pathology, Institute of Gerontology, University of Michigan, and Ann Arbor Department of Veterans Affairs Medical Center, Ann Arbor.

BACKGROUND: Little is known about the number or chromosomal location of genetic loci that might identify individuals destined to have a long life span. Analysis of gene/life span associations in mice, which are short-lived compared to humans, might provide guidance of the genetic basis of life span in humans. METHODS: A group of 144 genetically heterogenous mice, produced by a four-way cross between two F1 hybrid mouse stocks, was genotyped at 82 loci, and the mice were allowed to live either until their natural deaths or until they became extremely ill. Each mouse was also necropsied to determine the probable cause of death. An analysis of variance was used to seek relationships between life span (dependent variable) and the independent variables sex and allele for each marker locus. RESULTS: Five markers on different chromosomes were associated with differential longevity in male mice, and two other markers were associated with longevity in female mice. Post hoc probabilities were suggestive but not definitive, reaching p<.003 for the four strongest effects. Associations between marker loci and life span were sex-specific in almost all cases, affecting either males or females but not both. The strongest effects led to differences in mean survival of about 20% in the affected sex. The survival curves are consistent with the idea that the markers are linked to loci that influence the mortality risks of the longest-lived animals in the cohort. Associations between markers and life span did not appear to reflect associations of these markers to specific diseases in these mice. CONCLUSIONS: Associations between genetic markers and life span in mice bred by using a four-way cross are strong enough to deserve further analysis and seem to be sex-specific in their effects.

This article has been cited by other articles:

				J. W. Curtsinger Sex Specificity, Life-Span QTLs, and Statistical Power J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2002; 57(12): B409 - 414. [Abstract] [Full Text] [PDF]

				S. I.S. RATTAN Biogerontology: The Next Step Ann. N.Y. Acad. Sci., June 1, 2000; 908(1): 282 - 290. [Abstract] [Full Text] [PDF]

				A. U. Jackson, A. T. Galecki, D. T. Burke, and R. A. Miller Mouse Loci Associated With Life Span Exhibit Sex-Specific and Epistatic Effects J. Gerontol. A Biol. Sci. Med. Sci., January 1, 2002; 57(1): B9 - 15. [Abstract] [Full Text] [PDF]

				S. Klebanov, C. M. Astle, T. H. Roderick, K. Flurkey, J. R. Archer, J. Chen, and D. E. Harrison Maximum Life Spans in Mice Are Extended by Wild Strain Alleles Experimental Biology and Medicine, October 1, 2001; 226(9): 854 - 859. [Abstract] [Full Text] [PDF]

				R. A. Kerber, E. O'Brien, K. R. Smith, and R. M. Cawthon Familial Excess Longevity in Utah Genealogies J. Gerontol. A Biol. Sci. Med. Sci., February 1, 2001; 56(3): 130B - 139. [Abstract] [Full Text]

				R. A. Miller, C. Chrisp, and W. Atchley Differential Longevity in Mouse Stocks Selected for Early Life Growth Trajectory J. Gerontol. A Biol. Sci. Med. Sci., September 1, 2000; 55(9): 455B - 461. [Abstract] [Full Text]