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a Department of Pathology, University of Michigan School of Medicine, Institute of Gerontology, University of Michigan, and Ann Arbor DVA Medical Center
b Unit for Laboratory Animal Medicine, University of Michigan School of Medicine, Ann Arbor
c Department of Genetics, North Carolina State University, Raleigh
Richard A. Miller, Room 5316 CCGCB, Box 0940, University of Michigan, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0940 E-mail: millerr{at}umich.edu.
Decision Editor: Jay Roberts, PhD
Small body size is associated with superior longevity in several intraspecies comparisons, including dogs bred for specific forms of work, mice and rats fed diets low in calories, rats fed diets low in methionine, and mutant mice whose levels of growth hormone and thyroid hormone are atypically low. To further investigate the interactions among body size, genetic endowment, and longevity, we measured the life span of female mice selectively bred from Institute for Cancer Research stock for differences in rate of body weight gain. These mice were selected for differential rates of growth either early (0–10 days) or later (26–56 days) in the first 2 months of life. The data show a good correlation between the average weight of the stock and its mean longevity, with low body size associated, as predicted, with longer life span. Weight at 3, 6, and 12 months, and weight at peak body weight, are all significant predictors of longevity (among stocks) in univariate regressions; weight at 6 months has the strongest association in stepwise multiple regression. There is no significant correlation between the life span for the stock and the proportion of deaths attributable to neoplasia in this group of mice. The data provide support for the hypothesis that genetic factors that influence early life growth trajectories can have a strong influence on life span. These size-selected mice provide useful tools for analysis of the genetic factors that influence life history parameters, including maturation and aging rates.
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  N. Wolf, A. Galecki, R. Lipman, S. Chen, M. Smith-Wheelock, D. Burke, and R. Miller Quantitative Trait Locus Mapping for Age-Related Cataract Severity and Synechia Prevalence Using Four-Way Cross Mice Invest. Ophthalmol. Vis. Sci., June 1, 2004; 45(6): 1922 - 1929. [Abstract] [Full Text] [PDF]
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 R. N. Butler, S. N. Austad, N. Barzilai, A. Braun, S. Helfand, P. L. Larsen, A. M. McCormick, T. T. Perls, A. R. Shuldiner, R. L. Sprott, and H. R. Warner Longevity Genes: From Primitive Organisms to Humans J. Gerontol. A Biol. Sci. Med. Sci., July 1, 2003; 58(7): B581 - 584. [Full Text] [PDF]
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J. E. Morley Editorial: Citations, Impact Factor, and the Journal J. Gerontol. A Biol. Sci. Med. Sci., December 1, 2002; 57(12): M765 - 769. [Full Text] [PDF]
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 R. A. Miller, J. M. Harper, R. C. Dysko, S. J. Durkee, and S. N. Austad Longer Life Spans and Delayed Maturation in Wild-Derived Mice Experimental Biology and Medicine, July 1, 2002; 227(7): 500 - 508. [Abstract] [Full Text] [PDF]
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I. Dozmorov, A. Galecki, Y. Chang, R. Krzesicki, M. Vergara, and R. A. Miller Gene Expression Profile of Long-Lived Snell Dwarf Mice J. Gerontol. A Biol. Sci. Med. Sci., March 1, 2002; 57(3): B99 - 108. [Abstract] [Full Text] [PDF]
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 K. Flurkey, J. Papaconstantinou, R. A. Miller, and D. E. Harrison Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production PNAS, June 5, 2001; 98(12): 6736 - 6741. [Abstract] [Full Text] [PDF]
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