title: Increased serum IGF-1 levels protect the musculoskeletal system but are associated with elevated oxidative stress markers and increased mortality independent of tissue igf1 gene expression.
abstract: Although the literature suggests a protective (anabolic) effect of insulin-like growth factor-1 (IGF-1) on the musculoskeletal system during growth and aging, there is evidence that reductions in IGF-1 signaling are advantageous for promoting an increase in life span through reduction in oxidative stress-induced tissue damage. To better understand this paradox, we utilized the hepatocyte-specific IGF-1 transgenic (HIT) mice, which exhibit 3-fold increases in serum IGF-1, with normal IGF-1 expression in other tissues, and mice with an IGF-1 null background that exclusively express IGF-1 in the liver, which thereby deliver IGF-1 by the endocrine route only (KO-HIT mice). We found that in the total absence of tissue igf1 gene expression (KO-HIT), increases in serum IGF-1 levels were associated with increased levels of lipid peroxidation products in serum and increased mortality rate at 18 months of age in both genders. Surprisingly, however, we found that in female mice, tissue IGF-1 plays an important role in preserving trabecular bone architecture as KO-HIT mice show bone loss in the femoral distal metaphysis. Additionally, in male KO-HIT mice, increases in serum IGF-1 levels were insufficient to protect against age-related muscle loss.
authors.affiliation: Mount Sinai School of Medicine, New York, NY 10029, USA.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Elis
authors.forename: YingJie
authors.initials: Y
authors.lastname: Wu
authors.forename: Hayden-William
authors.initials: HW
authors.lastname: Courtland
authors.forename: Hui
authors.initials: H
authors.lastname: Sun
authors.forename: Clifford J
authors.initials: CJ
authors.lastname: Rosen
authors.forename: Martin L
authors.initials: ML
authors.lastname: Adamo
authors.forename: Shoshana
authors.initials: S
authors.lastname: Yakar
mesh_terms: D000375:Aging; D000818:Animals; D001846:Bone Development / Q000235:genetics; D005260:Female; D015870:Gene Expression; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D028421:Isoprostanes / Q000032:analysis / Q000096:biosynthesis; D015227:Lipid Peroxidation; D008099:Liver / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality; D008136:Longevity; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D023421:Models, Animal; D009141:Musculoskeletal System / Q000378:metabolism* / Q000473:pathology; D018384:Oxidative Stress; D012737:Sex Factors; D013274:Stomach Neoplasms / Q000235:genetics / Q000378:metabolism / Q000401:mortality
chemical_list: D028421:Isoprostanes; C519530:insulin-like growth factor-1, mouse; D007334:Insulin-Like Growth Factor I