Diverse roles of growth hormone and insulin-like growth factor-1 in mammalian aging: Progress and controversies

Journals of Gerontology - Series A Biological Sciences and Medical Sciences

Volumn 67 A, Issue 6, 2012, Pages 587-598

  Sonntag, William E ^a   Csiszar, Anna ^a   De Cabo, Raphael ^b   Ferrucci, Luigi ^b   Ungvari, Zoltan ^a  

^a UNIVERSITY OF ARKANSAS FOR MEDICAL SCIENCES   (United States)

^b NATIONAL INSTITUTE ON AGING   (United States)

Author keywords

Growth hormone; IGF 1; Longevity

Indexed keywords

ANIMALIA; MAMMALIA;

GROWTH HORMONE; INSULIN; SOMATOMEDIN BINDING PROTEIN; SOMATOMEDIN C;

AGING; ANIMAL; CELL TRANSFORMATION; DRUG EFFECT; FEMALE; GENETICS; HUMAN; LONGEVITY; MALE; METABOLISM; MOUSE; PHYSIOLOGY; RAT; REVIEW;

AGING; ANIMALS; CELL TRANSFORMATION, NEOPLASTIC; FEMALE; GROWTH HORMONE; HUMANS; INSULIN; INSULIN-LIKE GROWTH FACTOR BINDING PROTEINS; INSULIN-LIKE GROWTH FACTOR I; LONGEVITY; MALE; MICE; RATS;

EID: 84861039990     PISSN: 10795006     EISSN: 1758535X     Source Type: Journal    
DOI: 10.1093/gerona/gls115     Document Type: Review

References (91)

1. Novosyadlyy R, LeRoith D. Insulin-like growth factors and insulin: at the crossroad between tumor development and longevity. J Gerontol A Biol Sci Med Sci. 2012; In press.
2. Higashi Y, Sukhanov S, Shai SY, Delafontaine P. Aging, atherosclerosis, and IGF-1. J Gerontol A Biol Sci Med Sci. 2012; In press.
3. Ungvari Z, Csiszar A. The emerging role of IGF-1 deficiency in cardiovascular aging: recent advances. J Gerontol A Biol Sci Med Sci. 2012; In press.
4. Brown-Borg HM, Bartke A. GH and IGF1: roles in energy metabolism of long-living GH mutant mice. J Gerontol A Biol Sci Med Sci. 2012; In press.
5. Deak F, Sonntag WE. Aging, synaptic dysfunction and insulin-like growth factor-1. J Gerontol A Biol Sci Med Sci. 2012; In press.
6. Kenyon C, Chang J, Gensch E, Rudner A, Tabtiang RAC. Elegans mutant that lives twice as long as wild type. Nature. 1993;366:461-464. (Pubitemid 24013878)
7. Dillin A, Crawford DK, Kenyon C. Timing requirements for insulin/IGF-1 signaling in C. elegans. Science. 2002;298:830-834. (Pubitemid 35231536)
8. Kimura KD, Tissenbaum HA, Liu Y, Ruvkun G. Daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science. 1997;277:942-946. (Pubitemid 27366677)
9. Ogg S, Paradis S, Gottlieb S, et al. The fork head transcription factor DAF-16 transduces insulin-like metabolic and longevity signals in C. elegans. Nature. 1997;389:994-999. (Pubitemid 27485694)
10. Lin K, Dorman JB, Rodan A, Kenyon C. Daf-16: an HNF-3/forkhead family member that can function to double the life-span of Caenorhabditis elegans. Science. 1997;278:1319-1322. (Pubitemid 27495748)
11. Wolkow CA, Kimura KD, Lee MS, Ruvkun G. Regulation of C. elegans life-span by insulin like signaling in the nervous system. Science. 2000;290:147-150.
12. Kimura KD, Riddle DL, Ruvkun G. The C. elegans DAF-2 insulin-like receptor is abundantly expressed in the nervous system and regulated by nutritional status. Cold Spring Harb Symp Quant Biol. 2011.
13. Broughton SJ, Piper MD, Ikeya T, et al. Longer lifespan, altered metabolism, and stress resistance in Drosophila from ablation of cells making insulin-like ligands. Proc Natl Acad Sci USA. 2005;102:3105-3110. (Pubitemid 40299923)
14. Broughton S, Partridge L. Insulin/IGF-like signalling, the central nervous system and aging. Biochem J. 2009;418:1-12.
15. Wessells RJ, Fitzgerald E, Cypser JR, Tatar M, Bodmer R. Insulin regulation of heart function in aging fruit flies. Nat Genet. 2004;36:1275-1281. (Pubitemid 39577935)
16. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996;384:33.
17. Tatar M, Bartke A, Antebi A. The endocrine regulation of aging by insulin-like signals. Science. 2003;299:1346-1351. (Pubitemid 36254639)
18. Sonntag WE, Ramsey MM. Of worms, flies, dwarfs, and things that go bump in the night. Sci Aging Knowledge Environ. 2002;2002:pe17.
19. Carter CS, Ramsey MM, Sonntag WE. A critical analysis of the role of growth hormone and IGF-1 in aging and lifespan. Trends Genet. 2002;18:295-301. (Pubitemid 34607119)
20. Bartke A, Chandrashekar V, Bailey B, Zaczek D, Turyn D. Consequences of growth hormone (GH) overexpression and GH resistance. Neuropeptides. 2002;36:201-208.
21. Ikeno Y, Bronson RT, Hubbard GB, Lee S, Bartke A. Delayed occurrence of fatal neoplastic diseases in ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci. 2003;58:291-296. (Pubitemid 36397045)
22. Flurkey K, Papaconstantinou J, Miller RA, Harrison DE. Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA. 2001;98:6736-6741. (Pubitemid 32538286)
23. Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ. Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology. 2000;141:2608-2613. (Pubitemid 32269083)
24. Holzenberger M, Dupont J, Ducos B, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2003;421:182-187. (Pubitemid 36090987)
25. Bokov AF, Garg N, Ikeno Y, et al. Does reduced IGF-1R signaling in Igf1r +-mice alter aging? PLoS One. 2011;6:e26891.
26. Conover CA, Bale LK. Loss of pregnancy-associated plasma protein A extends lifespan in mice. Aging Cell. 2007;6:727-729. (Pubitemid 47400055)
27. Conover CA, Bale LK, Grell JA, Mader JR, Mason MA. Longevity is not influenced by prenatal programming of body size. Aging Cell. 2010;9:647-649.
28. Selman C, Lingard S, Choudhury AI, et al. Evidence for lifespan extension and delayed age-related biomarkers in insulin receptor substrate 1 null mice. FASEB J. 2008;22:807-818. (Pubitemid 351348133)
29. Selman C, Partridge L, Withers DJ. Replication of extended lifespan phenotype in mice with deletion of insulin receptor substrate 1. PLoS One. 2011;6:e16144.
30. Taguchi A, Wartschow LM, White MF. Brain IRS2 signaling coordinates life span and nutrient homeostasis. Science. 2007;317:369-372. (Pubitemid 47106376)
31. Shimokawa I, Higami Y, Utsuyama M, et al. Life span extension by reduction in growth hormone-insulin-like growth factor-1 axis in a transgenic rat model. Am J Pathol. 2002;160:2259-2265. (Pubitemid 34663416)
32. Sonntag WE, Carter CS, Ikeno Y, et al. Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span. Endocrinology. 2005;146:2920-2932. (Pubitemid 41002799)
33. Ladiges W, Van Remmen H, Strong R, et al. Lifespan extension in genetically modified mice. Aging Cell. 2009;8:346-352.
34. Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, et al. Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med. 2011;3:70ra13.
35. Laron Z. Do deficiencies in growth hormone and insulin-like growth factor-1 (IGF-1) shorten or prolong longevity? Mech Ageing Dev. 2005;126:305-307. (Pubitemid 40044749)
36. Burgers AM, Biermasz NR, Schoones JW, et al. Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality. J Clin Endocrinol Metab. 2011;96:2912-2920.
37. Renehan AG, Zwahlen M, Minder C, O'Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363:1346-1353. (Pubitemid 38529873)
38. Bonafe M, Barbieri M, Marchegiani F, et al. Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab. 2003;88:3299-3304. (Pubitemid 36877508)
39. Suh Y, Atzmon G, Cho MO, et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA. 2008;105:3438-3442. (Pubitemid 351723571)
40. Wang M, Zhang X, Zhao H, Wang Q, Pan Y. FoxO gene family evolution in vertebrates. BMC Evol Biol. 2009;9:222.
41. Burgering BM, Kops GJ. Cell cycle and death control: long live forkheads. Trends Biochem Sci. 2002;27:352-360. (Pubitemid 34756518)
42. Stahl M, Dijkers PF, Kops GJ, et al. The forkhead transcription factor FoxO regulates transcription of p27Kip1 and Bim in response to IL-2. J Immunol. 2002;168:5024-5031. (Pubitemid 34495965)
43. Accili D, Arden KC. FoxOs at the crossroads of cellular metabolism, differentiation, and transformation. Cell. 2004;117:421-426. (Pubitemid 38610228)
44. Willcox BJ, Donlon TA, He Q, et al. FOXO3A genotype is strongly associated with human longevity. Proc Natl Acad Sci USA. 2008;105:13987-13992.
45. Anselmi CV, Malovini A, Roncarati R, et al. Association of the FOXO3A locus with extreme longevity in a southern Italian centenarian study. Rejuvenation Res. 2009;12:95-104.
46. Flachsbart F, Caliebe A, Kleindorp R, et al. Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA. 2009;106:2700-2705.
47. Li Y, Wang WJ, Cao H, et al. Genetic association of FOXO1A and FOXO3A with longevity trait in Han Chinese populations. Hum Mol Genet. 2009;18:4897-4904.
48. Soerensen M, Dato S, Christensen K, et al. Replication of an association of variation in the FOXO3A gene with human longevity using both case-control and longitudinal data. Aging Cell. 2010;9:1010-1017.
49. Pawlikowska L, Hu D, Huntsman S, et al. Association of common genetic variation in the insulin/IGF1 signaling pathway with human longevity. Aging Cell. 2009;8:460-472.
50. Kleindorp R, Flachsbart F, Puca AA, Malovini A, Schreiber S, Nebel A. Candidate gene study of FOXO1, FOXO4, and FOXO6 reveals no association with human longevity in Germans. Aging Cell. 2011;10:622-628.
51. Bluher M, Kahn BB, Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science. 2003;299:572-574. (Pubitemid 36135156)
52. Back K, Brannmark C, Stralfors P, Arnqvist HJ. Differential effects of IGF-I, IGF-II and insulin in human preadipocytes and adipocytes-role of insulin and IGF-I receptors. Mol Cell Endocrinol. 2011;339:130-135.
53. Seely BL, Reichart DR, Takata Y, Yip C, Olefsky JM. A functional assessment of insulin/insulin-like growth factor-I hybrid receptors. Endocrinology. 1995;136:1635-1641.
54. Tartare-Deckert S, Sawka-Verhelle D, Murdaca J, Van Obberghen E. Evidence for a differential interaction of SHC and the insulin receptor substrate-1 (IRS-1) with the insulin-like growth factor-I (IGF-I) receptor in the yeast two-hybrid system. J Biol Chem. 1995;270:23456-23460.
55. Johansson GS, Arnqvist HJ. Insulin and IGF-I action on insulin receptors, IGF-I receptors, and hybrid insulin/IGF-I receptors in vascular smooth muscle cells. Am J Physiol Endocrinol Metab. 2006;291:E1124-E1130.
56. Ramsey MM, Ingram RL, Cashion AB, et al. Growth hormone-deficient dwarf animals are resistant to dimethylbenzanthracine (DMBA)-induced mammary carcinogenesis. Endocrinology. 2002;143:4139-4142. (Pubitemid 35244394)
57. Samani AA, Yakar S, LeRoith D, Brodt P. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocr Rev. 2007;28:20-47. (Pubitemid 46220849)
58. Bartke A, Brown-Borg H. Life extension in the dwarf mouse. Curr Top Dev Biol. 2004;63:189-225. (Pubitemid 39752388)
59. Barton ER. The ABCs of IGF-I isoforms: impact on muscle hypertrophy and implications for repair. Appl Physiol Nutr Metab. 2006;31:791-797.
60. Barton ER. Viral expression of insulin-like growth factor-I isoforms promotes different responses in skeletal muscle. J Appl Physiol. 2006;100:1778-1784. (Pubitemid 43845850)
61. Barton ER, DeMeo J, Lei H. The insulin-like growth factor (IGF)-I E-peptides are required for isoform-specific gene expression and muscle hypertrophy after local IGF-I production. J Appl Physiol. 2010;108:1069-1076.
62. Matheny RW Jr, Nindl BC, Adamo ML. Minireview: mechano-growth factor: a putative product of IGF-I gene expression involved in tissue repair and regeneration. Endocrinology. 2010;151:865-875.
63. Yakar S, Liu JL, Stannard B, et al. Normal growth and development in the absence of hepatic insulin-like growth factor I. Proc Natl Acad Sci USA. 1999;96:7324-7329. (Pubitemid 29299660)
64. Mitschelen M, Yan H, Farley JA, et al. Long-term deficiency of circulating and hippocampal insulin-like growth factor I induces depressive behavior in adult mice: a potential model of geriatric depression. Neuroscience. 2011;185:50-60.
65. Sun LY, Al-Regaiey K, Masternak MM, Wang J, Bartke A. Local expression of GH and IGF-1 in the hippocampus of GH-deficient long-lived mice. Neurobiol Aging. 2005;26:929-937. (Pubitemid 40249496)
66. Kawai M, Rosen CJ. The IGF-I regulatory system and its impact on skeletal and energy homeostasis. J Cell Biochem. 2010;111:14-19.
67. Baxter RC, Twigg SM. Actions of IGF binding proteins and related proteins in adipose tissue. Trends Endocrinol Metab. 2009;20:499-505.
68. Firth SM, Baxter RC. Cellular actions of the insulin-like growth factor binding proteins. Endocr Rev. 2002;23:824-854. (Pubitemid 35454590)
69. Bunn RC, Fowlkes JL. Insulin-like growth factor binding protein proteolysis. Trends Endocrinol Metab. 2003;14:176-181. (Pubitemid 36733903)
70. Conover CA, Bale LK, Mader JR, Mason MA, Keenan KP, Marler RJ. Longevity and age-related pathology of mice deficient in pregnancy-associated plasma protein-A. J Gerontol A Biol Sci Med Sci. 2010;65:590-599.
71. Kandalla PK, Goldspink G, Butler-Browne G, Mouly V. Mechano growth factor E peptide (MGF-E), derived from an isoform of IGF-1, activates human muscle progenitor cells and induces an increase in their fusion potential at different ages. Mech Ageing Dev. 2011;132:154-162.
72. Delbono O. Regulation of excitation contraction coupling by insulin-like growth factor-1 in aging skeletal muscle. J Nutr Health Aging. 2000;4:162-164.
73. Gonzalez E, Messi ML, Zheng Z, Delbono O. Insulin-like growth factor-1 prevents age-related decrease in specific force and intracellular Ca2+ in single intact muscle fibres from transgenic mice. J Physiol. 2003;552:833-844. (Pubitemid 37428424)
74. Bailey-Downs LC, Sosnowska D, Toth P, et al. Growth hormone and IGF-1 deficiency exacerbate high-fat diet-induced endothelial impairment in obese Lewis dwarf rats: implications for vascular aging. J Gerontol A Biol Sci Med Sci. 2011.
75. Masternak MM, Panici JA, Bonkowski MS, Hughes LF, Bartke A. Insulin sensitivity as a key mediator of growth hormone actions on longevity. J Gerontol A Biol Sci Med Sci. 2009;64:516-521.
76. Sonntag WE, Steger RW, Forman LJ, Meites J. Decreased pulsatile release of growth hormone in old male rats. Endocrinology. 1980;107:1875-1879. (Pubitemid 11194700)
77. Carter CS, Ramsey MM, Ingram RL, et al. Models of growth hormone and IGF-1 deficiency: applications to studies of aging processes and life-span determination. J Gerontol A Biol Sci Med Sci. 2002;57:B177-B188. (Pubitemid 34464960)
78. Corpas E, Harman SM, Blackman MR. Human growth hormone and human aging. Endocr Rev. 1993;14:20-39. (Pubitemid 23066530)
79. Sonntag WE, Lynch C, Thornton P, Khan A, Bennett S, Ingram R. The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing;. J Anat. 2000;197(Pt 4):575-585. (Pubitemid 32051538)
80. Ramsey MM, Weiner JL, Moore TP, Carter CS, Sonntag WE. Growth hormone treatment attenuates age-related changes in hippocampal short-term plasticity and spatial learning. Neuroscience. 2004;129:119-127. (Pubitemid 39360948)
81. Rudman D, Feller AG, Nagraj HS, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990;323:1-6. (Pubitemid 20209464)
82. Nieves-Martinez E, Sonntag WE, Wilson A, et al. Early-onset GH deficiency results in spatial memory impairment in mid-life and is prevented by GH supplementation. J Endocrinol. 2010;204:31-36.
83. Panici JA, Harper JM, Miller RA, Bartke A, Spong A, Masternak MM. Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice. FASEB J. 2010;24:1-7.
84. Yuan R, Tsaih SW, Petkova SB, et al. Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels. Aging Cell. 2009;8:277-287.
85. Yuan R, Rosen CJ, Beamer WG. Aging study: IGF-1 and body weight for 33 inbred strains of mice. MPD: Yuan1. Mouse Phenome Database Web site. The Jackson Laboratory, Bar Harbor, ME. http://phenome.jax.org. Accessed: Feb 05, 2012.
86. Harper JM, Salmon AB, Leiser SF, Galecki AT, Miller RA. Skin-derived fibroblasts from long-lived species are resistant to some, but not all, lethal stresses and to the mitochondrial inhibitor rotenone. Aging Cell. 2007;6:1-13. (Pubitemid 46140135)
87. Murakami S, Salmon A, Miller RA. Multiplex stress resistance in cells from long-lived dwarf mice. FASEB J. 2003;17:1565-1566.
88. Salmon AB, Murakami S, Bartke A, Kopchick J, Yasumura K, Miller RA. Fibroblast cell lines from young adult mice of long-lived mutant strains are resistant to multiple forms of stress. Am J Physiol Endocrinol Metab. 2005;289:E23-E29. (Pubitemid 40874930)
89. Ungvari Z, Sosnowska D, Podlutsky A, Koncz P, Sonntag WE, Csiszar A. Free radical production, antioxidant capacity, and oxidative stress response signatures in fibroblasts from Lewis dwarf rats: effects of life span-extending peripubertal GH treatment. J Gerontol A Biol Sci Med Sci. 2011;66:501-510.
90. Wu Y, Brodt P, Sun H, et al. Insulin-like growth factor-I regulates the liver microenvironment in obese mice and promotes liver metastasis. Cancer Res. 2010;70:57-67.
91. Bailey-Downs LC, Mitschelen M, Sosnowska D, et al. Liver-specific knockdown of IGF-1 decreases vascular oxidative stress resistance by impairing the Nrf2-dependent antioxidant response: a novel model of vascular aging. J Gerontol A Biol Sci Med Sci. 2011; In press.