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Genetic Modulation of Hormone Levels and Life Span in Hybrids Between Laboratory and Wild-Derived Mice

¹ Department of Pathology and Geriatrics Center, University of Michigan School of Medicine, Ann Arbor.
² Ann Arbor Department of Veterans Affairs Medical Center, Michigan.
³ Unit for Laboratory Animal Medicine, University of Michigan, Ann Arbor.
⁴ Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio.

Address correspondence to James M. Harper, PhD, University of Michigan, 190 Zina Pitcher Pl., Room 3005, BSRB Box 2200, Ann Arbor, MI 48109-2200. E-mail: jmharper{at}umich.edu

Previously we showed that mouse stocks derived from wild-caught progenitors are long-lived relative to genetically heterogeneous mice derived from laboratory-adapted strains. Here we replicate this life-span effect, and show that F2 hybrids between wild-derived and laboratory-derived stocks have intermediate survival patterns. Moreover, wild-derived mice are small, lean, and slow to mature, and have low serum insulin-like growth factor-I (IGF-I) relative to genetically heterogeneous mice. These traits, too, were at intermediate levels in the F2 hybrids. Furthermore, serum IGF-I at 6 months was a significant predictor of life span in two different populations of F2 hybrid mice. Pooling across stocks, life span was negatively correlated with body weight and serum IGF-I levels, and positively correlated with age at vaginal patency and serum leptin levels. Overall, these finding suggest that wild-derived mice harbor alleles that increase longevity, perhaps through effects on growth, maturation, and early-life hormone levels.

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