BMB Reports 2019; 52(1): 70-85  
Growth signaling and longevity in mouse models
Seung-Soo Kim1 & Cheol-Koo Lee1,2,*
1Institute of Animal Molecular Biotechnology, Korea University, Seoul 02841, 2Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul 02481, Korea
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Received: November 19, 2018; Published online: January 31, 2019.
© Korean Society for Biochemistry and Molecular Biology. All rights reserved.

Reduction of insulin/insulin-like growth factor 1 (IGF1) signaling (IIS) extends the lifespan of various species. So far, several longevity mouse models have been developed containing mutations related to growth signaling deficiency by targeting growth hormone (GH), IGF1, IGF1 receptor, insulin receptor, and insulin receptor substrate. In addition, p70 ribosomal protein S6 kinase 1 (S6K1) knockout leads to lifespan extension. S6K1 encodes an important kinase in the regulation of cell growth. S6K1 is regulated by mechanistic target of rapamycin (mTOR) complex 1. The v-myc myelocytomatosis viral oncogene homolog (MYC)-deficient mice also exhibits a longevity phenotype. The gene expression profiles of these mice models have been measured to identify their longevity mechanisms. Here, we summarize our knowledge of long-lived mouse models related to growth and discuss phenotypic characteristics, including organ-specific gene expression patterns.
Keywords: Gene expression, Growth signaling, Longevity, Mouse model
Fig. 1. GH-IIS axis and hepatic gene expression patterns in long-lived mice. Components of the GH-IIS axis impact on hepatic gene expression and affect longevity. We divided GH-IIS axis genetically-modified mouse models into four groups: 1) GH signal-deficient mice with mutation at genes affecting GH production and GH signaling, 2) IGF1-reduced mice with homozygous and heterozygous mutation at genes involved in IGF1 production, including IGF1R and IR, 3) IRS-deficient mice including homozygous and heterozygous mutations of Irs1 and Irs2, and 4) mTORC1- and MYC-reduced mice with homozygous and heterozygous mutations for reduction of mTORC1 levels, lack of S6K1, p66Shc deficiency, and lower MYC levels. The target genes for long-lived mouse models are written in bolded red. Downstream liver gene expression patterns for longevity are displayed on the bottom panel.

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