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Growth hormone and aging

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Abstract

Growth hormone (GH) actions impact growth, metabolism, and body composition and have been associated with aging and longevity. Lack of GH results in slower growth, delayed maturation, and reduced body size and can lead to delayed aging, increased healthspan, and a remarkable extension of longevity. Adult body size, which is a GH-dependent trait, has a negative association with longevity in several mammalian species. Mechanistic links between GH and aging include evolutionarily conserved insulin/insulin-like growth factors and mechanistic target of rapamycin signaling pathways in accordance with long-suspected trade-offs between anabolic/growth processes and longevity. Height and the rate and regulation of GH secretion have been related to human aging, but longevity is not extended in humans with syndromes of GH deficiency or resistance. However, the risk of age-related chronic disease is reduced in individuals affected by these syndromes and various indices of increased healthspan have been reported.

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References

  1. Silberberg R. Articular aging and osteoarthrosis in dwarf mice. Pathol Microbiol (Basel). 1972;38(6):417–30.

    CAS  Google Scholar 

  2. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996;384(6604):33.

    Article  CAS  PubMed  Google Scholar 

  3. 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 U S A. 2001;98(12):6736–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Li S, Crenshaw EB III, Rawson EJ, Simmons DM, Swanson LW, Rosenfeld MG. Dwarf locus mutants lacking three pituitary cell types result from mutations in the POU-domain gene pit-1. Nature. 1990;347(6293):528–33.

    Article  CAS  PubMed  Google Scholar 

  5. Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O'Connell SM, et al. Pituitary lineage determination by the prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature. 1996;384(6607):327–33.

    Article  CAS  PubMed  Google Scholar 

  6. Coschigano KT, Clemmons D, Bellush LL, Kopchick JJ. Assessment of growth parameters and life span of GHR/BP gene-disrupted mice. Endocrinology. 2000;141(7):2608–13.

    Article  CAS  PubMed  Google Scholar 

  7. Zhou Y, Xu BC, Maheshwari HG, He L, Reed M, Lozykowski M, et al. 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. 1997;94(24):13215–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, Kopchick JJ. 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. 2003;144(9):3799–810.

    Article  CAS  PubMed  Google Scholar 

  9. Bonkowski MS, Rocha JS, Masternak MM, al Regaiey KA, Bartke A. Targeted disruption of growth hormone receptor interferes with the beneficial actions of calorie restriction. Proc Natl Acad Sci U S A. 2006;103(20):7901–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Yuan R, Tsaih SW, Petkova SB, de Evsikova CM, Xing S, Marion MA, et al. Aging in inbred strains of mice: study design and interim report on median lifespans and circulating IGF1 levels. Aging Cell. 2009;8(3):277–87.

    Article  CAS  PubMed  Google Scholar 

  11. Holzenberger M, Kappeler L, De Magalhaes Filho C. IGF-1 signaling and aging. Exp Gerontol. 2004;39(11–12):1761–4.

    Article  CAS  PubMed  Google Scholar 

  12. Alba M, Salvatori R. A mouse with targeted ablation of the growth hormone-releasing hormone gene: a new model of isolated growth hormone deficiency. Endocrinology. 2004;145(9):4134–43.

    Article  CAS  PubMed  Google Scholar 

  13. Sun LY, Spong A, Swindell WR, Fang Y, Hill C, Huber JA, et al. Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. Elife. 2013;2:e01098.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  14. 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(12):5073–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Sun LY, Fang Y, Patki A, Koopman JJE, Allison DB, Hill CM, et al. Longevity is impacted by growth hormone action during early postnatal period. Elife. 2017;6.

  16. Bartke A. Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice. Neuroendocrinology. 2003;78(4):210–6.

    Article  CAS  PubMed  Google Scholar 

  17. Wanke R, Wolf E, Hermanns W, Folger S, Buchmüller T, Brem G. The GH-transgenic mouse as an experimental model for growth research: clinical and pathological studies. Horm Res. 1992;37(Suppl 3):74–87.

    Article  PubMed  Google Scholar 

  18. Bartke A. Single-gene mutations and healthy ageing in mammals. Philos Trans R Soc Lond Ser B Biol Sci. 2011;366(1561):28–34.

    Article  CAS  Google Scholar 

  19. Aguiar-Oliveira MH, Bartke A. Growth hormone deficiency: health and longevity. Endocr Rev. 2019;40(2):575–601.

    Article  PubMed  Google Scholar 

  20. Kinney BA, Meliska CJ, Steger RW, Bartke A. Evidence that Ames dwarf mice age differently from their normal siblings in behavioral and learning and memory parameters. Horm Behav. 2001;39(4):277–84.

    Article  CAS  PubMed  Google Scholar 

  21. Kinney BA, Coschigano KT, Kopchick JJ, Steger RW, Bartke A. Evidence that age-induced decline in memory retention is delayed in growth hormone resistant GH-R-KO (Laron) mice. Physiol Behav. 2001;72(5):653–60.

    Article  CAS  PubMed  Google Scholar 

  22. Arum O, Rasche ZA, Rickman DJ, Bartke A. Prevention of neuromusculoskeletal frailty in slow-aging Ames dwarf mice: longitudinal investigation of interaction of longevity genes and caloric restriction. PLoS One. 2013;8(10):e72255.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Arum O, Rickman DJ, Kopchick JJ, Bartke A. The slow-aging growth hormone receptor/binding protein gene-disrupted (GHR-KO) mouse is protected from aging-resultant neuromusculoskeletal frailty. Age (Dordr). 2014;36(1):117–27.

    Article  CAS  Google Scholar 

  24. Ikeno Y, et al. Delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci. 2003;58(4):291–6.

    Article  PubMed  Google Scholar 

  25. Ikeno Y, et al. Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor/binding protein knockout mice. J Gerontol A Biol Sci Med Sci. 2009;64(5):522–9.

    Article  PubMed  CAS  Google Scholar 

  26. Alderman JM, Flurkey K, Brooks NL, Naik SB, Gutierrez JM, Srinivas U, et al. Neuroendocrine inhibition of glucose production and resistance to cancer in dwarf mice. Exp Gerontol. 2009;44(1–2):26–33.

    Article  CAS  PubMed  Google Scholar 

  27. Koopman JJ, et al. Measuring aging rates of mice subjected to caloric restriction and genetic disruption of growth hormone signaling. Aging (Albany NY). 2016;8(3):539–46.

    Article  CAS  Google Scholar 

  28. Wang T, Tsui B, Kreisberg JF, Robertson NA, Gross AM, Yu MK, et al. Epigenetic aging signatures in mice livers are slowed by dwarfism, calorie restriction and rapamycin treatment. Genome Biol. 2017;18(1):57.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  29. Cole JJ, Robertson NA, Rather MI, Thomson JP, McBryan T, Sproul D, et al. Diverse interventions that extend mouse lifespan suppress shared age-associated epigenetic changes at critical gene regulatory regions. Genome Biol. 2017;18(1):58.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018;19(6):371–84.

    Article  CAS  PubMed  Google Scholar 

  31. Petkovich DA, Podolskiy DI, Lobanov AV, Lee SG, Miller RA, Gladyshev VN. Using DNA methylation profiling to evaluate biological age and longevity interventions. Cell Metab. 2017;25(4):954–60 e6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Puig KL, Kulas JA, Franklin W, Rakoczy SG, Taglialatela G, Brown-Borg HM, et al. The Ames dwarf mutation attenuates Alzheimer's disease phenotype of APP/PS1 mice. Neurobiol Aging. 2016;40:22–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Tallaksen-Greene SJ, Sadagurski M, Zeng L, Mauch R, Perkins M, Banduseela VC, et al. Differential effects of delayed aging on phenotype and striatal pathology in a murine model of Huntington disease. J Neurosci. 2014;34(47):15658–68.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Dominick G, Berryman DE, List EO, Kopchick JJ, Li X, Miller RA, et al. Regulation of mTOR activity in Snell dwarf and GH receptor gene-disrupted mice. Endocrinology. 2015;156(2):565–75.

    Article  PubMed  CAS  Google Scholar 

  35. Sharp ZD, Bartke A. Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in Ames dwarf mice. J Gerontol A Biol Sci Med Sci. 2005;60(3):293–300.

    Article  PubMed  Google Scholar 

  36. Fang Y, Hill CM, Darcy J, Reyes-Ordoñez A, Arauz E, McFadden S, et al. Effects of rapamycin on growth hormone receptor knockout mice. Proc Natl Acad Sci U S A. 2018;115(7):E1495–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Masternak MM, Bartke A, Wang F, Spong A, Gesing A, Fang Y, et al. Metabolic effects of intra-abdominal fat in GHRKO mice. Aging Cell. 2012;11(1):73–81.

    Article  CAS  PubMed  Google Scholar 

  38. Spadaro O, Goldberg EL, Camell CD, Youm YH, Kopchick JJ, Nguyen KY, et al. Growth hormone receptor deficiency protects against age-related NLRP3 Inflammasome activation and immune senescence. Cell Rep. 2016;14(7):1571–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Masternak MM, et al. Insulin sensitivity as a key mediator of growth hormone actions on longevity. J Gerontol A Biol Sci Med Sci. 2009;64(5):516–21.

    Article  PubMed  CAS  Google Scholar 

  40. Brown-Borg HM, Rakoczy S, Wonderlich JA, Armstrong V, Rojanathammanee L. Altered dietary methionine differentially impacts glutathione and methionine metabolism in long-living growth hormone-deficient Ames dwarf and wild-type mice. Longev Healthspan. 2014;3(1):10.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Brown-Borg HM. The somatotropic axis and longevity in mice. Am J Physiol Endocrinol Metab. 2015;309(6):E503–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Darcy J, et al. Brown adipose tissue function is enhanced in long-lived. Male Ames Dwarf Mice Endocrinol. 2016;157(12):4744–53.

    CAS  Google Scholar 

  43. Li Y, Knapp JR, Kopchick JJ. Enlargement of interscapular brown adipose tissue in growth hormone antagonist transgenic and in growth hormone receptor gene-disrupted dwarf mice. Exp Biol Med (Maywood). 2003;228(2):207–15.

    Article  CAS  Google Scholar 

  44. Darcy J, Bartke A. From white to Brown - adipose tissue is critical to the extended lifespan and Healthspan of growth hormone mutant mice. Adv Exp Med Biol. 2019;1178:207–25.

    Article  CAS  PubMed  Google Scholar 

  45. Westbrook R, et al. Alterations in oxygen consumption, respiratory quotient, and heat production in long-lived GHRKO and Ames dwarf mice, and short-lived bGH transgenic mice. J Gerontol A Biol Sci Med Sci. 2009;64(4):443–51.

    Article  PubMed  CAS  Google Scholar 

  46. Podlutsky A, Valcarcel-Ares MN, Yancey K, Podlutskaya V, Nagykaldi E, Gautam T, et al. The GH/IGF-1 axis in a critical period early in life determines cellular DNA repair capacity by altering transcriptional regulation of DNA repair-related genes: implications for the developmental origins of cancer. Geroscience. 2017;39(2):147–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Dominick G, Bowman J, Li X, Miller RA, Garcia GG. mTOR regulates the expression of DNA damage response enzymes in long-lived Snell dwarf, GHRKO, and PAPPA-KO mice. Aging Cell. 2017;16(1):52–60.

    Article  CAS  PubMed  Google Scholar 

  48. Stout MB, Tchkonia T, Pirtskhalava T, Palmer AK, List EO, Berryman DE, et al. Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging (Albany NY). 2014;6(7):575–86.

    Article  Google Scholar 

  49. Garcia AM, Busuttil RA, Calder RB, Dollé MET, Diaz V, McMahan CA, et al. Effect of Ames dwarfism and caloric restriction on spontaneous DNA mutation frequency in different mouse tissues. Mech Ageing Dev. 2008;129(9):528–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Saccon TD, et al. Primordial follicle reserve, DNA damage and macrophage infiltration in the ovaries of the long-living. Ames Dwarf Mice Exp Gerontol. 2020;132:110851.

    Article  CAS  PubMed  Google Scholar 

  51. Schneider A, Matkovich SJ, Saccon T, Victoria B, Spinel L, Lavasani M, et al. Ovarian transcriptome associated with reproductive senescence in the long-living Ames dwarf mice. Mol Cell Endocrinol. 2017;439:328–36.

    Article  CAS  PubMed  Google Scholar 

  52. Sluczanowska-Glabowska S, et al. Morphology of ovaries in laron dwarf mice, with low circulating plasma levels of insulin-like growth factor-1 (IGF-1), and in bovine GH-transgenic mice, with high circulating plasma levels of IGF-1. J Ovarian Res. 2012;5:18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Baker DJ, Wijshake T, Tchkonia T, LeBrasseur NK, Childs BG, van de Sluis B, et al. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479(7372):232–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Palmer AK, Xu M, Zhu Y, Pirtskhalava T, Weivoda MM, Hachfeld CM, et al. Targeting senescent cells alleviates obesity-induced metabolic dysfunction. Aging Cell. 2019;18(3):e12950.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Dozmorov I, Galecki A, Chang Y, Krzesicki R, Vergara M, Miller RA. Gene expression profile of long-lived snell dwarf mice. J Gerontol A Biol Sci Med Sci. 2002;57(3):B99–108.

    Article  PubMed  Google Scholar 

  56. Tsuchiya T, Dhahbi JM, Cui X, Mote PL, Bartke A, Spindler SR. Additive regulation of hepatic gene expression by dwarfism and caloric restriction. Physiol Genomics. 2004;17(3):307–15.

    Article  CAS  PubMed  Google Scholar 

  57. 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(1):E23–9.

    Article  CAS  PubMed  Google Scholar 

  58. Pickering AM, Lehr M, Kohler WJ, Han ML, Miller RA. Fibroblasts from longer-lived species of Primates, rodents, bats, carnivores, and birds resist protein damage. J Gerontol A Biol Sci Med Sci. 2015;70(7):791–9.

    Article  CAS  PubMed  Google Scholar 

  59. Johnson TE, Cypser J, de Castro E, de Castro S, Henderson S, Murakami S, et al. Gerontogenes mediate health and longevity in nematodes through increasing resistance to environmental toxins and stressors. Exp Gerontol. 2000;35(6–7):687–94.

    Article  CAS  PubMed  Google Scholar 

  60. Bates DJ, Li N, Liang R, Sarojini H, An J, Masternak MM, et al. MicroRNA regulation in Ames dwarf mouse liver may contribute to delayed aging. Aging Cell. 2010;9(1):1–18.

    Article  CAS  PubMed  Google Scholar 

  61. Swindell WR. Gene expression profiling of long-lived dwarf mice: longevity-associated genes and relationships with diet, gender and aging. BMC Genomics. 2007;8:353.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  62. Masternak MM, al-Regaiey KA, del Rosario Lim MM, Jimenez-Ortega V, Panici JA, Bonkowski MS, et al. Effects of caloric restriction on insulin pathway gene expression in the skeletal muscle and liver of normal and long-lived GHR-KO mice. Exp Gerontol. 2005;40(8–9):679–84.

    Article  CAS  PubMed  Google Scholar 

  63. List EO, Berryman DE, Funk K, Gosney ES, Jara A, Kelder B, et al. The role of GH in adipose tissue: lessons from adipose-specific GH receptor gene-disrupted mice. Mol Endocrinol. 2013;27(3):524–35.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. List EO, Berryman DE, Funk K, Jara A, Kelder B, Wang F, et al. Liver-specific GH receptor gene-disrupted (LiGHRKO) mice have decreased endocrine IGF-I, increased local IGF-I, and altered body size, body composition, and adipokine profiles. Endocrinology. 2014;155(5):1793–805.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. List EO, Berryman DE, Ikeno Y, Hubbard GB, Funk K, Comisford R, et al. Removal of growth hormone receptor (GHR) in muscle of male mice replicates some of the health benefits seen in global GHR−/− mice. Aging (Albany NY). 2015;7(7):500–12.

    Article  CAS  Google Scholar 

  66. Ungvari Z, et al. Vasoprotective effects of life span-extending peripubertal GH replacement in Lewis dwarf rats. J Gerontol A Biol Sci Med Sci. 2010;65(11):1145–56.

  67. Rollo CD. Growth negatively impacts the life span of mammals. Evol Dev. 2002;4(1):55–61.

    Article  PubMed  Google Scholar 

  68. Junnila RK, Duran-Ortiz S, Suer O, Sustarsic EG, Berryman DE, List EO, et al. Disruption of the GH receptor gene in adult mice increases maximal lifespan in females. Endocrinology. 2016;157(12):4502–13.

    Article  CAS  PubMed  Google Scholar 

  69. Roberts RC. The lifetime growth and reproduction of selected strains of mice. Heredity. 1961;16:369–81.

    Article  Google Scholar 

  70. Eklund J, Bradford CE. Longevity and lifetime body weight in mice selected for rapid growth. Nature. 1977;265:48–9.

    Article  CAS  PubMed  Google Scholar 

  71. Miller RA, Harper JM, Galecki A, Burke DT. Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice. Aging Cell. 2002;1(1):22–9.

    Article  CAS  PubMed  Google Scholar 

  72. Yuan R, Meng Q, Nautiyal J, Flurkey K, Tsaih SW, Krier R, et al. Genetic coregulation of age of female sexual maturation and lifespan through circulating IGF1 among inbred mouse strains. Proc Natl Acad Sci U S A. 2012;109(21):8224–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Patronek GJ, Waters DJ, Glickman LT. Comparative longevity of pet dogs and humans: implications for gerontology research. J Gerontol A Biol Sci Med Sci. 1997;52(3):B171–8.

    Article  CAS  PubMed  Google Scholar 

  74. Brosnahan MM, Paradis MR. Demographic and clinical characteristics of geriatric horses: 467 cases (1989-1999). J Am Vet Med Assoc. 2003;223(1):93–8.

    Article  PubMed  Google Scholar 

  75. Samaras TT. Human body size and the laws of scaling: physiological, performance, growth, longevity and ecological ramifications. New York: Nova Science Publishers, Inc.; 2007.

    Google Scholar 

  76. He Q, Morris BJ, Grove JS, Petrovitch H, Ross W, Masaki KH, et al. Shorter men live longer: association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. PLoS One. 2014;9(5):e94385.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  77. van der Spoel E, Jansen SW, Akintola AA, Ballieux BE, Cobbaert CM, Slagboom PE, et al. Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity. Aging Cell. 2016;15(6):1126–31.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  78. Westendorp RG, et al. Nonagenarian siblings and their offspring display lower risk of mortality and morbidity than sporadic nonagenarians: the Leiden longevity study. J Am Geriatr Soc. 2009;57(9):1634–7.

    Article  PubMed  Google Scholar 

  79. Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci U S A. 2008;105(9):3438–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Milman S, Atzmon G, Huffman DM, Wan J, Crandall JP, Cohen P, et al. Low insulin-like growth factor-1 level predicts survival in humans with exceptional longevity. Aging Cell. 2014;13(4):769–71.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Burgers AM, et al. Meta-analysis and dose-response metaregression: circulating insulin-like growth factor I (IGF-I) and mortality. J Clin Endocrinol Metab. 2011;96(9):2912–20.

    Article  CAS  PubMed  Google Scholar 

  82. Colao A, Ferone D, Marzullo P, Lombardi G. Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev. 2004;25(1):102–52.

    Article  CAS  PubMed  Google Scholar 

  83. Holdaway IM, Rajasoorya RC, Gamble GD. Factors influencing mortality in acromegaly. J Clin Endocrinol Metab. 2004;89(2):667–74.

    Article  CAS  PubMed  Google Scholar 

  84. Holdaway IM, Bolland MJ, Gamble GD. A meta-analysis of the effect of lowering serum levels of GH and IGF-I on mortality in acromegaly. Eur J Endocrinol. 2008;159(2):89–95.

    Article  CAS  PubMed  Google Scholar 

  85. Wolinski K, Stangierski A, Dyrda K, Nowicka K, Pelka M, Iqbal A, et al. Risk of malignant neoplasms in acromegaly: a case-control study. J Endocrinol Investig. 2017;40(3):319–22.

    Article  CAS  Google Scholar 

  86. Dal J, Leisner MZ, Hermansen K, Farkas DK, Bengtsen M, Kistorp C, et al. Cancer incidence in patients with acromegaly: a cohort study and meta-analysis of the literature. J Clin Endocrinol Metab. 2018;103(6):2182–8.

    Article  PubMed  Google Scholar 

  87. Pendergrass WR, Li Y, Jiang DZ, Wolf NS. Decrease in cellular replicative potential in "giant" mice transfected with the bovine growth hormone gene correlates to shortened life span. J Cell Physiol. 1993;156(1):96–103.

    Article  CAS  PubMed  Google Scholar 

  88. Wolf E, Kahnt E, Ehrlein J, Hermanns W, Brem G, Wanke R. Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: lessons from transgenic animal models. Mech Ageing Dev. 1993;68(1–3):71–87.

    Article  CAS  PubMed  Google Scholar 

  89. Guevara-Aguirre J, Guevara A, Palacios I, Pérez M, Prócel P, Terán E. GH and GHR signaling in human disease. Growth Hormon IGF Res. 2018;38:34–8.

    Article  CAS  Google Scholar 

  90. Tseng FY, Chen ST, Chen JF, Huang TS, Lin JD, Wang PW, et al. Correlations of clinical parameters with quality of life in patients with acromegaly: Taiwan acromegaly registry. J Formos Med Assoc. 2019;118(11):1488–93.

    Article  PubMed  Google Scholar 

  91. Fabris N, Pierpaoli W, Sorkin E. Hormones and the immunological capacity. 3. The immunodeficiency disease of the hypopituitary Snell-Bagg dwarf mouse. Clin Exp Immunol. 1971;9(2):209–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Schneider GB. Immunological competence in Snell-Bagg pituitary dwarf mice: response to the contact-sensitizing agent oxazolone. Am J Anat. 1976;145(3):371–93.

    Article  CAS  PubMed  Google Scholar 

  93. Shire JG. Growth hormone and premature ageing. Nature. 1973;245(5422):215–6.

    Article  CAS  PubMed  Google Scholar 

  94. Silberberg R. Vertebral aging in hypopituitary dwarf mice. Gerontologia. 1973;19(5):281–94.

    Article  CAS  PubMed  Google Scholar 

  95. Rudman D, Feller AG, Nagraj HS, Gergans GA, Lalitha PY, Goldberg AF, et al. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990;323:1–6.

    Article  CAS  PubMed  Google Scholar 

  96. Gharib H, Cook DM, Saenger PH, Bengtsson BA, Feld S, Nippoldt TB, et al. American Association of Clinical Endocrinologists medical guidelines for clinical practice for growth hormone use in adults and children--2003 update. Endocr Pract. 2003;9(1):64–76.

    Article  PubMed  Google Scholar 

  97. Fahy GM, Brooke RT, Watson JP, Good Z, Vasanawala SS, Maecker H, et al. Reversal of epigenetic aging and immunosenescent trends in humans. Aging Cell. 2019;18(6):e13028.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Carter CS, Richardson A, Huffman DM, Austad S. Bring Back the rat! J Gerontol A Biol Sci Med Sci. 2020;75(3):405–15.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Besson A, Salemi S, Gallati S, Jenal A, Horn R, Mullis PS, et al. Reduced longevity in untreated patients with isolated growth hormone deficiency. J Clin Endocrinol Metab. 2003;88(8):3664–7.

    Article  CAS  PubMed  Google Scholar 

  100. Morris JZ, Tissenbaum HA, Ruvkun G. A phosphatidylinositol-3-OH kinase family member regulating longevity and diapause in Caenorhabditis elegans. Nature. 1996;382(6591):536–9.

    Article  CAS  PubMed  Google Scholar 

  101. Kimura KD, et al. Daf-2, an insulin receptor-like gene that regulates longevity and diapause in Caenorhabditis elegans. Science. 1997;277(5328):942–6.

    Article  CAS  PubMed  Google Scholar 

  102. Bitto A, et al. Biochemical Genetic Pathways that Modulate Aging in Multiple Species. Cold Spring Harb Perspect Med. 2015:5(11).

  103. Bartke A, Sun LY, Longo V. Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev. 2013;93(2):571–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Maklakov AA, Chapman T. Evolution of ageing as a tangle of trade-offs: energy versus function. Proc Biol Sci. 2019;286(1911):20191604.

    CAS  PubMed  PubMed Central  Google Scholar 

  105. Hao J, Yin Y, Fei S-z. Brassinosteroid signaling network: implications on yield and stress tolerance. Plant Cell Rep. 2013;32(7):1017–30.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We apologize to those whose work pertinent to the issues discussed was not cited due to limitations of the format or to inadvertent omissions. We are grateful for editorial assistance provided by Lisa Hensley and Dr. Tracy Evans.

Funding

This work was supported by the American Diabetes Association grant ADA 1–19-IBS-126 and the William E. McElroy Charitable Foundation.

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  1. Southern Illinois University School of Medicine, 801 N. Rutledge, P.O. Box 19628, Springfield, IL, 62794-9628, USA

    Andrzej Bartke

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A. Bartke wrote this manuscript.

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Correspondence to Andrzej Bartke.

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Bartke, A. Growth hormone and aging. Rev Endocr Metab Disord 22, 71–80 (2021). https://doi.org/10.1007/s11154-020-09593-2

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