title: Mice producing reduced levels of insulin-like growth factor type 1 display an increase in maximum, but not mean, life span.
abstract: Reduced signaling through the IGF type 1 (IGF-1) receptor increases life span in multiple invertebrate organisms. Studies on mammalian longevity suggest that reducing levels of IGF-1 may also increase life span. However, the data are conflicting and complicated by the physiology of the mammalian neuroendocrine system. We have performed life-span analysis on mice homozygous for an insertion in the Igf1 gene. These mice produce reduced levels of IGF-1 and display a phenotype consistent with a significant decrease in IGF-1. Life-span analysis was carried out at three independent locations. Although the life-span data varied between sites, the maximum life span of the IGF-1-deficient mice was significantly increased and age-specific mortality rates were reduced in the IGF-1-deficient mice; however, mean life span did not differ except at one site, where mean life span was increased in female IGF-1-deficient animals. Early life mortality was noted in one cohort of IGF-1-deficient mice. The results are consistent with a significant role for IGF-1 in the modulation of life span but contrast with the published life-span data for the hypopituitary Ames and Snell dwarf mice and growth hormone receptor null mice, indicating that a reduction in IGF-1 alone is insufficient to increase both mean and maximal life span in mice.
authors.affiliation: Department of Pathology, Drexel University COM, 245 N 15th Street, Philadelphia, PA 19102. Christian.sell@dexelmed.edu.
authors.forename: Antonello
authors.initials: A
authors.lastname: Lorenzini
authors.forename: Adam B
authors.initials: AB
authors.lastname: Salmon
authors.forename: Chad
authors.initials: C
authors.lastname: Lerner
authors.forename: Claudio
authors.initials: C
authors.lastname: Torres
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.forename: Susan
authors.initials: S
authors.lastname: Motch
authors.forename: Roger
authors.initials: R
authors.lastname: McCarter
authors.forename: Christian
authors.initials: C
authors.lastname: Sell
mesh_terms: D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005260:Female; D018507:Gene Expression Regulation, Developmental; D005838:Genotype; D007334:Insulin-Like Growth Factor I / Q000172:deficiency* / Q000235:genetics; D008136:Longevity / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D007334:Insulin-Like Growth Factor I
keywords: Gluconeogenesis.; IGF-1; Insulin; Metabolism; Obesity