Browse > Article
http://dx.doi.org/10.5483/BMBRep.2019.52.1.299

Growth signaling and longevity in mouse models  

Kim, Seung-Soo (Institute of Animal Molecular Biotechnology, Korea University)
Lee, Cheol-Koo (Institute of Animal Molecular Biotechnology, Korea University)
Publication Information
BMB Reports / v.52, no.1, 2019 , pp. 70-85 More about this Journal
Abstract
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;
Citations & Related Records
연도 인용수 순위
  • Reference
1 Bonafe M and Olivieri F (2009) Genetic polymorphism in long-lived people: cues for the presence of an insulin/IGF-pathway-dependent network affecting human longevity. Mol Cell Endocrinol 299, 118-123   DOI
2 Junnila RK, List EO, Berryman DE, Murrey JW and Kopchick JJ (2013) The GH/IGF-1 axis in ageing and longevity. Nat Rev Endocrinol 9, 366-376   DOI
3 Zhang J and Liu F (2014) Tissue-specific insulin signaling in the regulation of metabolism and aging. IUBMB Life 66, 485-495   DOI
4 Rask-Madsen C and Kahn CR (2012) Tissue-specific insulin signaling, metabolic syndrome, and cardiovascular disease. Arterioscler Thromb Vasc Biol 32, 2052-2059   DOI
5 Flurkey K, Papaconstantinou J, Miller RA and Harrison DE (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci U S A 98, 6736-6741   DOI
6 Flurkey K, Papaconstantinou J and Harrison DE (2002) The Snell dwarf mutation Pit1(dw) can increase life span in mice. Mech Ageing Dev 123, 121-130   DOI
7 Lin L, Hale SP and Schimmel P (1996) Aminoacylation error correction. Nature 384, 33-34
8 Zhou Y, Xu BC, Maheshwari HG et al (1997) A mammalian model for Laron syndrome produced by targeted disruption of the mouse growth hormone receptor/binding protein gene (the Laron mouse). Proc Natl Acad Sci U S A 94, 13215-13220   DOI
9 Coschigano KT, Clemmons D, Bellush LL and Kopchick JJ (2000) Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology 141, 2608-2613   DOI
10 Chen WY, Wight DC, Mehta BV, Wagner TE and Kopchick JJ (1991) Glycine 119 of bovine growth hormone is critical for growth-promoting activity. Mol Endocrinol 5, 1845-1852   DOI
11 Yang CW, Striker LJ, Pesce C et al (1993) Glomerulosclerosis and body growth are mediated by different portions of bovine growth hormone. Studies in transgenic mice. Lab Invest 68, 62-70
12 Chanson P and Salenave S (2008) Acromegaly. Orphanet J Rare Dis 3, 17   DOI
13 MacLeod JN, Pampori NA and Shapiro BH (1991) Sex differences in the ultradian pattern of plasma growth hormone concentrations in mice. J Endocrinol 131, 395-399   DOI
14 van der Pluijm I, Garinis GA, Brandt RM et al (2007) Impaired genome maintenance suppresses the growth hormone--insulin-like growth factor 1 axis in mice with Cockayne syndrome. PLoS Biol 5, e2   DOI
15 Schumacher B, van der Pluijm I, Moorhouse MJ et al (2008) Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet 4, e1000161   DOI
16 Jansson JO, Eden S and Isaksson O (1985) Sexual dimorphism in the control of growth hormone secretion. Endocr Rev 6, 128-150   DOI
17 Mode A and Gustafsson JA (2006) Sex and the liver - a journey through five decades. Drug Metab Rev 38, 197-207   DOI
18 Dozmorov I, Galecki A, Chang Y, Krzesicki R, Vergara M and Miller RA (2002) Gene expression profile of long-lived snell dwarf mice. J Gerontol A Biol Sci Med Sci 57, B99-108   DOI
19 Clayton PE, Banerjee I, Murray PG and Renehan AG (2011) Growth hormone, the insulin-like growth factor axis, insulin and cancer risk. Nat Rev Endocrinol 7, 11-24   DOI
20 Dozmorov I, Bartke A and Miller RA (2001) Array-based expression analysis of mouse liver genes: effect of age and of the longevity mutant Prop1df. J Gerontol A Biol Sci Med Sci 56, B72-80   DOI
21 Amador-Noguez D, Yagi K, Venable S and Darlington G (2004) Gene expression profile of long-lived Ames dwarf mice and Little mice. Aging Cell 3, 423-441   DOI
22 Boylston WH, Gerstner A, DeFord JH et al (2004) Altered cholesterologenic and lipogenic transcriptional profile in livers of aging Snell dwarf (Pit1dw/dwJ) mice. Aging Cell 3, 283-296   DOI
23 Tsuchiya T, Dhahbi JM, Cui X, Mote PL, Bartke A and Spindler SR (2004) Additive regulation of hepatic gene expression by dwarfism and caloric restriction. Physiol Genomics 17, 307-315   DOI
24 Amador-Noguez D, Zimmerman J, Venable S and Darlington G (2005) Gender-specific alterations in gene expression and loss of liver sexual dimorphism in the long-lived Ames dwarf mice. Biochem Biophys Res Commun 332, 1086-1100   DOI
25 Papaconstantinou J, Deford JH, Gerstner A et al (2005) Hepatic gene and protein expression of primary components of the IGF-I axis in long lived Snell dwarf mice. Mech Ageing Dev 126, 692-704   DOI
26 Clodfelter KH, Miles GD, Wauthier V et al (2007) Role of STAT5a in regulation of sex-specific gene expression in female but not male mouse liver revealed by microarray analysis. Physiol Genomics 31, 63-74   DOI
27 Waxman DJ and O'Connor C (2006) Growth hormone regulation of sex-dependent liver gene expression. Mol Endocrinol 20, 2613-2629   DOI
28 Yang X, Schadt EE, Wang S et al (2006) Tissue-specific expression and regulation of sexually dimorphic genes in mice. Genome Res 16, 995-1004   DOI
29 Clodfelter KH, Holloway MG, Hodor P, Park SH, Ray WJ and Waxman DJ (2006) Sex-dependent liver gene expression is extensive and largely dependent upon signal transducer and activator of transcription 5b (STAT5b): STAT5b-dependent activation of male genes and repression of female genes revealed by microarray analysis. Mol Endocrinol 20, 1333-1351   DOI
30 Niedernhofer LJ, Garinis GA, Raams A et al (2006) A new progeroid syndrome reveals that genotoxic stress suppresses the somatotroph axis. Nature 444, 1038-1043   DOI
31 Bokov AF, Garg N, Ikeno Y et al (2011) Does reduced IGF-1R signaling in Igf1r+/- mice alter aging? PLoS One 6, e26891   DOI
32 Yakar S, Liu JL, Stannard B et al (1999) Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci U S A 96, 7324-7329   DOI
33 Svensson J, Sjogren K, Faldt J et al (2011) Liver-derived IGF-I regulates mean life span in mice. PLoS One 6, e22640   DOI
34 Novosyadlyy R and Leroith D (2012) Insulin-like growth factors and insulin: at the crossroad between tumor development and longevity. J Gerontol A Biol Sci Med Sci 67, 640-651   DOI
35 Ladiges W, Van Remmen H, Strong R et al (2009) Lifespan extension in genetically modified mice. Aging Cell 8, 346-352   DOI
36 Kurosu H, Yamamoto M, Clark JD et al (2005) Suppression of aging in mice by the hormone Klotho. Science 309, 1829-1833   DOI
37 Kuro-o M, Matsumura Y, Aizawa H et al (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390, 45-51   DOI
38 Selman C, Lingard S, Choudhury AI et al (2008) Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J 22, 807-818   DOI
39 Peng J and He L (2018) IRS posttranslational modifications in regulating insulin signaling. J Mol Endocrinol 60, R1-R8   DOI
40 Previs SF, Withers DJ, Ren JM, White MF and Shulman GI (2000) Contrasting effects of IRS-1 versus IRS-2 gene disruption on carbohydrate and lipid metabolism in vivo. J Biol Chem 275, 38990-38994   DOI
41 Webb AE, Kundaje A and Brunet A (2016) Characterization of the direct targets of FOXO transcription factors throughout evolution. Aging Cell 15, 673-685   DOI
42 Hannenhalli S and Kaestner KH (2009) The evolution of Fox genes and their role in development and disease. Nat Rev Genet 10, 233-240   DOI
43 Shimokawa I, Komatsu T, Hayashi N et al (2015) The life-extending effect of dietary restriction requires Foxo3 in mice. Aging Cell 14, 707-709   DOI
44 Boehm AM, Khalturin K, Anton-Erxleben F et al (2012) FoxO is a critical regulator of stem cell maintenance in immortal Hydra. Proc Natl Acad Sci U S A 109, 19697-19702   DOI
45 Bluher M, Michael MD, Peroni OD et al (2002) Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell 3, 25-38   DOI
46 Selman C, Partridge L and Withers DJ (2011) Replication of extended lifespan phenotype in mice with deletion of insulin receptor substrate 1. PLoS One 6, e16144   DOI
47 Page MM, Schuster EF, Mudaliar M, Herzyk P, Withers DJ and Selman C (2018) Common and unique transcriptional responses to dietary restriction and loss of insulin receptor substrate 1 (IRS1) in mice. Aging (Albany NY) 10, 1027-1052   DOI
48 Stout MB, Tchkonia T, Pirtskhalava T et al (2014) Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging (Albany NY) 6, 575-586   DOI
49 Stout MB, Swindell WR, Zhi X et al (2015) Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice. Oncotarget 6, 26702-26715   DOI
50 Masternak MM, Bartke A, Wang F et al (2012) Metabolic effects of intra-abdominal fat in GHRKO mice. Aging Cell 11, 73-81   DOI
51 Bluher M, Patti ME, Gesta S, Kahn BB and Kahn CR (2004) Intrinsic heterogeneity in adipose tissue of fat-specific insulin receptor knock-out mice is associated with differences in patterns of gene expression. J Biol Chem 279, 31891-31901   DOI
52 Wang S and Ren J (2018) Obesity Paradox in Aging: From Prevalence to Pathophysiology. Prog Cardiovasc Dis 61, 182-189   DOI
53 Tomilov AA, Bicocca V, Schoenfeld RA et al (2010) Decreased superoxide production in macrophages of long-lived p66Shc knock-out mice. J Biol Chem 285, 1153-1165   DOI
54 Wientjes FB and Segal AW (1995) NADPH oxidase and the respiratory burst. Semin Cell Biol 6, 357-365   DOI
55 Dang CV (2012) MYC on the path to cancer. Cell 149, 22-35   DOI
56 Hofmann JW, Zhao X, De Cecco M et al (2015) Reduced expression of MYC increases longevity and enhances healthspan. Cell 160, 477-488   DOI
57 Bartke A (2012) Healthy aging: is smaller better? - a mini-review. Gerontology 58, 337-343   DOI
58 Murakami S (2006) Stress resistance in long-lived mouse models. Exp Gerontol 41, 1014-1019   DOI
59 Tower J (2017) Sex-Specific Gene Expression and Life Span Regulation. Trends Endocrinol Metab 28, 735-747   DOI
60 Barbieri M, Bonafe M, Franceschi C and Paolisso G (2003) Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab 285, E1064-1071   DOI
61 Fontana L, Partridge L and Longo VD (2010) Extending healthy life span--from yeast to humans. Science 328, 321-326   DOI
62 Hwangbo DS, Gershman B, Tu MP, Palmer M and Tatar M (2004) Drosophila dFOXO controls lifespan and regulates insulin signalling in brain and fat body. Nature 429, 562-566   DOI
63 Holzenberger M, Dupont J, Ducos B et al (2003) IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature 421, 182-187   DOI
64 Salminen A, Kaarniranta K and Kauppinen A (2017) Regulation of longevity by FGF21: Interaction between energy metabolism and stress responses. Ageing Res Rev 37, 79-93   DOI
65 Chen WY, White ME, Wagner TE and Kopchick JJ (1991) Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in dwarf transgenic mice. Endocrinology 129, 1402-1408   DOI
66 Berryman DE, List EO, Coschigano KT, Behar K, Kim JK and Kopchick JJ (2004) Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Horm IGF Res 14, 309-318   DOI
67 Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A and Kopchick JJ (2003) Deletion, but not antagonism, of the mouse growth hormone receptor results in severely decreased body weights, insulin, and insulin-like growth factor I levels and increased life span. Endocrinology 144, 3799-3810   DOI
68 Kuro-o M (2012) Klotho and betaKlotho. Adv Exp Med Biol 728, 25-40   DOI
69 Conover CA (2012) Key questions and answers about pregnancy-associated plasma protein-A. Trends Endocrinol Metab 23, 242-249   DOI
70 Sjogren K, Liu JL, Blad K et al (1999) Liver-derived insulin-like growth factor I (IGF-I) is the principal source of IGF-I in blood but is not required for postnatal body growth in mice. Proc Natl Acad Sci U S A 96, 7088-7092   DOI
71 Conover CA, Bale LK, Overgaard MT et al (2004) Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development. Development 131, 1187-1194   DOI
72 Doi T, Striker LJ, Quaife C et al (1988) Progressive glomerulosclerosis develops in transgenic mice chronically expressing growth hormone and growth hormone releasing factor but not in those expressing insulinlike growth factor-1. Am J Pathol 131, 398-403
73 Inagaki T, Lin VY, Goetz R, Mohammadi M, Mangelsdorf DJ and Kliewer SA (2008) Inhibition of growth hormone signaling by the fasting-induced hormone FGF21. Cell Metab 8, 77-83   DOI
74 Zhang Y, Xie Y, Berglund ED et al (2012) The starvation hormone, fibroblast growth factor-21, extends lifespan in mice. Elife 1, e00065   DOI
75 Bartke A (2003) Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice. Neuroendocrinology 78, 210-216   DOI
76 Jones JM, Morrell JC and Gould SJ (2000) Identification and characterization of HAOX1, HAOX2, and HAOX3, three human peroxisomal 2-hydroxy acid oxidases. J Biol Chem 275, 12590-12597   DOI
77 Boylston WH, DeFord JH and Papaconstantinou J (2006) Identification of longevity-associated genes in long-lived Snell and Ames dwarf mice. Age (Dordr) 28, 125-144   DOI
78 Rossner R, Kaeberlein M and Leiser SF (2017) Flavincontaining monooxygenases in aging and disease: Emerging roles for ancient enzymes. J Biol Chem 292, 11138-11146   DOI
79 Simard J, Ricketts ML, Gingras S, Soucy P, Feltus FA and Melner MH (2005) Molecular biology of the 3betahydroxysteroid dehydrogenase/delta5-delta4 isomerase gene family. Endocr Rev 26, 525-582   DOI
80 Rowland JE, Lichanska AM, Kerr LM et al (2005) In vivo analysis of growth hormone receptor signaling domains and their associated transcripts. Mol Cell Biol 25, 66-77   DOI
81 Barclay JL, Nelson CN, Ishikawa M et al (2011) GH-dependent STAT5 signaling plays an important role in hepatic lipid metabolism. Endocrinology 152, 181-192   DOI
82 Chang L, Qi H, Xiao Y et al (2016) Integrated analysis of noncoding RNAs and mRNAs reveals their potential roles in the biological activities of the growth hormone receptor. Growth Horm IGF Res 29, 11-20   DOI
83 Lorenzini A, Salmon AB, Lerner C et al (2014) Mice producing reduced levels of insulin-like growth factor type 1 display an increase in maximum, but not mean, life span. J Gerontol A Biol Sci Med Sci 69, 410-419   DOI
84 Conover CA and Bale LK (2007) Loss of pregnancyassociated plasma protein A extends lifespan in mice. Aging Cell 6, 727-729   DOI
85 Conover CA, Bale LK, Mader JR, Mason MA, Keenan KP and Marler RJ (2010) Longevity and age-related pathology of mice deficient in pregnancy-associated plasma protein-A. J Gerontol A Biol Sci Med Sci 65, 590-599
86 Liu JP, Baker J, Perkins AS, Robertson EJ and Efstratiadis A (1993) Mice carrying null mutations of the genes encoding insulin-like growth factor I (Igf-1) and type 1 IGF receptor (Igf1r). Cell 75, 59-72
87 Accili D, Drago J, Lee EJ et al (1996) Early neonatal death in mice homozygous for a null allele of the insulin receptor gene. Nat Genet 12, 106-109   DOI
88 Nelson JF, Strong R, Bokov A, Diaz V and Ward W (2012) Probing the relationship between insulin sensitivity and longevity using genetically modified mice. J Gerontol A Biol Sci Med Sci 67, 1332-1338   DOI
89 Kushner JA, Ye J, Schubert M et al (2002) Pdx1 restores beta cell function in Irs2 knockout mice. J Clin Invest 109, 1193-1201   DOI
90 Withers DJ, Gutierrez JS, Towery H et al (1998) Disruption of IRS-2 causes type 2 diabetes in mice. Nature 391, 900-904   DOI
91 Kushner JA, Haj FG, Klaman LD et al (2004) Islet-sparing effects of protein tyrosine phosphatase-1b deficiency delays onset of diabetes in IRS2 knockout mice. Diabetes 53, 61-66   DOI
92 Kushner JA, Simpson L, Wartschow LM et al (2005) Phosphatase and tensin homolog regulation of islet growth and glucose homeostasis. J Biol Chem 280, 39388-39393   DOI
93 Taguchi A and White MF (2008) Insulin-like signaling, nutrient homeostasis, and life span. Annu Rev Physiol 70, 191-212   DOI
94 Taguchi A, Wartschow LM and White MF (2007) Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science 317, 369-372   DOI
95 Selman C, Lingard S, Gems D, Partridge L and Withers DJ (2008) Comment on "Brain IRS2 signaling coordinates life span and nutrient homeostasis". Science 320, 1012; author reply 1012
96 Kubota N, Kubota T, Itoh S et al (2008) Dynamic functional relay between insulin receptor substrate 1 and 2 in hepatic insulin signaling during fasting and feeding. Cell Metab 8, 49-64   DOI
97 Katic M, Kennedy AR, Leykin I et al (2007) Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice. Aging Cell 6, 827-839   DOI
98 Swindell WR (2007) Gene expression profiling of long-lived dwarf mice: longevity-associated genes and relationships with diet, gender and aging. BMC Genomics 8, 353   DOI
99 Nicola NA and Babon JJ (2015) Leukemia inhibitory factor (LIF). Cytokine Growth Factor Rev 26, 533-544   DOI
100 Yano H, Readhead C, Nakashima M, Ren SG and Melmed S (1998) Pituitary-directed leukemia inhibitory factor transgene causes Cushing's syndrome: neuroimmune-endocrine modulation of pituitary development. Mol Endocrinol 12, 1708-1720   DOI
101 Guo S, Copps KD, Dong X et al (2009) The Irs1 branch of the insulin signaling cascade plays a dominant role in hepatic nutrient homeostasis. Mol Cell Biol 29, 5070-5083   DOI
102 Brunet A, Bonni A, Zigmond MJ et al (1999) Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857-868   DOI
103 Martins R, Lithgow GJ and Link W (2016) Long live FOXO: unraveling the role of FOXO proteins in aging and longevity. Aging Cell 15, 196-207   DOI
104 Ren J and Brown-Borg HM (2002) Impaired cardiac excitation-contraction coupling in ventricular myocytes from Ames dwarf mice with IGF-I deficiency. Growth Horm IGF Res 12, 99-105   DOI
105 Kappeler L, De Magalhaes Filho C, Dupont J et al (2008) Brain IGF-1 receptors control mammalian growth and lifespan through a neuroendocrine mechanism. PLoS Biol 6, e254   DOI
106 Sadagurski M, Cheng Z, Rozzo A et al (2011) IRS2 increases mitochondrial dysfunction and oxidative stress in a mouse model of Huntington disease. J Clin Invest 121, 4070-4081   DOI
107 Li Q and Ren J (2007) Influence of cardiac-specific overexpression of insulin-like growth factor 1 on lifespan and aging-associated changes in cardiac intracellular Ca2+ homeostasis, protein damage and apoptotic protein expression. Aging Cell 6, 799-806   DOI
108 Um SH, D'Alessio D and Thomas G (2006) Nutrient overload, insulin resistance, and ribosomal protein S6 kinase 1, S6K1. Cell Metab 3, 393-402   DOI
109 Selman C, Tullet JM, Wieser D et al (2009) Ribosomal protein S6 kinase 1 signaling regulates mammalian life span. Science 326, 140-144   DOI
110 Lamming DW, Ye L, Katajisto P et al (2012) Rapamycininduced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science 335, 1638-1643   DOI
111 Ranieri SC, Fusco S, Panieri E et al (2010) Mammalian life-span determinant p66shcA mediates obesity-induced insulin resistance. Proc Natl Acad Sci U S A 107, 13420-13425   DOI
112 Migliaccio E, Giorgio M, Mele S et al (1999) The p66shc adaptor protein controls oxidative stress response and life span in mammals. Nature 402, 309-313   DOI