Genetic modulation of hormone levels and life span in hybrids between laboratory and wild-derived mice.
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.
Harper
James M
JM
University of Michigan, 190 Zina Pitcher Pl., Room 3005, BSRB Box 2200, Ann Arbor, MI 48109-2200, USA. jmharper@umich.edu
Durkee
Stephen J
SJ
Dysko
Robert C
RC
Austad
Steven N
SN
Miller
Richard A
RA
D000305:Adrenal Cortex Hormones / Q000097:blood; D000375:Aging / Q000502:physiology; D000818:Animals; D000830:Animals, Laboratory; D000835:Animals, Wild; D001835:Body Weight; D002678:Chimera; D007334:Insulin-Like Growth Factor I / Q000032:analysis*; D020738:Leptin / Q000097:blood*; D008136:Longevity / Q000235:genetics*; D051379:Mice; D008815:Mice, Inbred Strains; D010641:Phenotype; D012741:Sexual Maturation; D013974:Thyroxine / Q000097:blood
D000305:Adrenal Cortex Hormones; D020738:Leptin; D007334:Insulin-Like Growth Factor I; D013974:Thyroxine