World J Mens Health.  2019 Jan;37(1):19-30. 10.5534/wjmh.180018.

Growth Hormone and Aging: Updated Review

Affiliations
  • 1Department of Internal Medicine, Southern Illinois University School of Medicine, Springfield, IL, USA. abartke@siumed.edu

Abstract

Role of growth hormone (GH) in mammalian aging is actively explored in clinical, epidemiological, and experimental studies. The age-related decline in GH levels is variously interpreted as a symptom of neuroendocrine aging, as one of causes of altered body composition and other unwelcome symptoms of aging, or as a mechanism of natural protection from cancer and other chronic diseases. Absence of GH signals due to mutations affecting anterior pituitary development, GH secretion, or GH receptors produces an impressive extension of longevity in laboratory mice. Extension of healthspan in these animals and analysis of survival curves suggest that in the absence of GH, aging is slowed down or delayed. The corresponding endocrine syndromes in the human have no consistent impact on longevity, but are associated with remarkable protection from age-related disease. Moreover, survival to extremely old age has been associated with reduced somatotropic (GH and insulin-like growth factor-1) signaling in women and men. In both humans and mice, elevation of GH levels into the supranormal (pathological) range is associated with increased disease risks and reduced life expectancy likely representing acceleration of aging. The widely advertised potential of GH as an anti-aging agent attracted much interest. However, results obtained thus far have been disappointing with few documented benefits and many troublesome side effects. Possible utility of GH in the treatment of sarcopenia and frailty remains to be explored.

Keyword

Aging; Growth hormone; Healthy aging; Life expectancy; Somatotropin

MeSH Terms

Acceleration
Aging*
Animals
Body Composition
Chronic Disease
Female
Growth Hormone*
Humans
Life Expectancy
Longevity
Male
Mice
Sarcopenia
Growth Hormone

Figure

  • Fig. 1 Key mechanisms mediating the effects of reduced growth hormone (GH) signaling on aging and longevity (↓decrease, ↑increase). IGF-1: insulin-like growth factor-1, mTORC1: mechanistic target of rapamycin complex 1.


Cited by  1 articles

Diagnosis and treatment of sexual dysfunction in elderly men
Hyun Jun Park
J Korean Med Assoc. 2019;62(6):308-314.    doi: 10.5124/jkma.2019.62.6.308.


Reference

1. Corpas E, Harman SM, Blackman MR. Human growth hormone and human aging. Endocr Rev. 1993; 14:20–39. PMID: 8491152.
Article
2. Veldhuis JD. Aging and hormones of the hypothalamo-pituitary axis: gonadotropic axis in men and somatotropic axes in men and women. Ageing Res Rev. 2008; 7:189–208. PMID: 18343203.
Article
3. Bartke A, Westendorp RGJ, van Heemst D. Endocrine systems. In : Vigj J, Campisi J, Lithgow GJ, editors. Molecular and cellular biology of aging. Washington, D.C.: Gerontological Society of America;2015. p. 250–274.
4. Müller EE, Cella SG, De Gennaro Colonna V, Parenti M, Cocchi D, Locatelli V. Aspects of the neuroendocrine control of growth hormone secretion in ageing mammals. J Reprod Fertil Suppl. 1993; 46:99–114. PMID: 8100277.
5. Sonntag WE, Steger RW, Forman LJ, Meites J. Decreased pulsatile release of growth hormone in old male rats. Endocrinology. 1980; 107:1875–1879. PMID: 7428695.
Article
6. Kuwahara S, Kesuma Sari D, Tsukamoto Y, Tanaka S, Sasaki F. Age-related changes in growth hormone (GH)-releasing hormone and somatostatin neurons in the hypothalamus and in GH cells in the anterior pituitary of female mice. Brain Res. 2004; 1025:113–122. PMID: 15464751.
Article
7. Maggio M, Ble A, Ceda GP, Metter EJ. Decline in insulin-like growth factor-I levels across adult life span in two large population studies. J Gerontol A Biol Sci Med Sci. 2006; 61:182–183. PMID: 16510863.
Article
8. Baxter RC. IGF binding proteins in cancer: mechanistic and clinical insights. Nat Rev Cancer. 2014; 14:329–341. PMID: 24722429.
Article
9. Clemmons DR. Modifying IGF1 activity: an approach to treat endocrine disorders, atherosclerosis and cancer. Nat Rev Drug Discov. 2007; 6:821–833. PMID: 17906644.
Article
10. 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. PMID: 2355952.
Article
11. Rosén T, Johannsson G, Johansson JO, Bengtsson BA. Consequences of growth hormone deficiency in adults and the benefits and risks of recombinant human growth hormone treatment. A review paper. Horm Res. 1995; 43:93–99. PMID: 7721271.
12. Salomon F, Cuneo RC, Hesp R, Sönksen PH. The effects of treatment with recombinant human growth hormone on body composition and metabolism in adults with growth hormone deficiency. N Engl J Med. 1989; 321:1797–1803. PMID: 2687691.
Article
13. Rosenfalck AM, Maghsoudi S, Fisker S, Jørgensen JO, Christiansen JS, Hilsted J, et al. The effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin and C-peptide kinetics, insulin secretion, insulin sensitivity, glucose effectiveness, and body composition in GH-deficient adults. J Clin Endocrinol Metab. 2000; 85:4173–4181. PMID: 11095450.
Article
14. Blackman MR, Sorkin JD, Münzer T, Bellantoni MF, Busby-Whitehead J, Stevens TE, et al. Growth hormone and sex steroid administration in healthy aged women and men: a randomized controlled trial. JAMA. 2002; 288:2282–2292. PMID: 12425705.
15. Liu H, Bravata DM, Olkin I, Nayak S, Roberts B, Garber AM, et al. Systematic review: the safety and efficacy of growth hormone in the healthy elderly. Ann Intern Med. 2007; 146:104–115. PMID: 17227934.
Article
16. Lange KH, Andersen JL, Beyer N, Isaksson F, Larsson B, Rasmussen MH, et al. GH administration changes myosin heavy chain isoforms in skeletal muscle but does not augment muscle strength or hypertrophy, either alone or combined with resistance exercise training in healthy elderly men. J Clin Endocrinol Metab. 2002; 87:513–523. PMID: 11836279.
Article
17. Taaffe DR, Pruitt L, Reim J, Hintz RL, Butterfield G, Hoffman AR, et al. Effect of recombinant human growth hormone on the muscle strength response to resistance exercise in elderly men. J Clin Endocrinol Metab. 1994; 79:1361–1366. PMID: 7525633.
Article
18. Swerdlow AJ, Cooke R, Beckers D, Borgström B, Butler G, Carel JC, et al. Cancer risks in patients treated with growth hormone in childhood: The SAGhE European Cohort Study. J Clin Endocrinol Metab. 2017; 102:1661–1672. PMID: 28187225.
Article
19. Boguszewski CL, Boguszewski MC, Kopchick JJ. Growth hormone, insulin-like growth factor system and carcinogenesis. Endokrynol Pol. 2016; 67:414–426. PMID: 27387246.
Article
20. Capalbo D, Barbieri F, Improda N, Giallauria F, Di Pietro E, Rapacciuolo A, et al. Growth hormone improves cardiopulmonary capacity and body composition in children with growth hormone deficiency. J Clin Endocrinol Metab. 2017; 102:4080–4088. PMID: 28938456.
Article
21. Sathiavageeswaran M, Burman P, Lawrence D, Harris AG, Falleti MG, Maruff P, et al. Effects of GH on cognitive function in elderly patients with adult-onset GH deficiency: a placebo-controlled 12-month study. Eur J Endocrinol. 2007; 156:439–447. PMID: 17389458.
Article
22. Moreau OK, Cortet-Rudelli C, Yollin E, Merlen E, Daveluy W, Rousseaux M. Growth hormone replacement therapy in patients with traumatic brain injury. J Neurotrauma. 2013; 30:998–1006. PMID: 23323993.
Article
23. Sattler FR. Growth hormone in the aging male. Best Pract Res Clin Endocrinol Metab. 2013; 27:541–555. PMID: 24054930.
Article
24. Perls TT, Reisman NR, Olshansky SJ. Provision or distribution of growth hormone for “antiaging”: clinical and legal issues. JAMA. 2005; 294:2086–2090. PMID: 16249424.
25. Nass R, Park J, Thorner MO. Growth hormone supplementation in the elderly. Endocrinol Metab Clin North Am. 2007; 36:233–245. PMID: 17336743.
Article
26. Friedman SD, Baker LD, Borson S, Jensen JE, Barsness SM, Craft S, et al. Growth hormone-releasing hormone effects on brain γ-aminobutyric acid levels in mild cognitive impairment and healthy aging. JAMA Neurol. 2013; 70:883–890. PMID: 23689947.
Article
27. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A. Dwarf mice and the ageing process. Nature. 1996; 384:33.
Article
28. 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; 98:6736–6741. PMID: 11371619.
Article
29. 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. PMID: 24175087.
Article
30. 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; 144:3799–3810. PMID: 12933651.
Article
31. Bartke A. Single-gene mutations and healthy ageing in mammals. Philos Trans R Soc Lond B Biol Sci. 2011; 366:28–34. PMID: 21115527.
Article
32. Brown-Borg HM. The somatotropic axis and longevity in mice. Am J Physiol Endocrinol Metab. 2015; 309:E503–E510. PMID: 26219867.
Article
33. Bartke A, Sun LY, Longo V. Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev. 2013; 93:571–598. PMID: 23589828.
Article
34. Koopman JJ, van Heemst D, van Bodegom D, Bonkowski MS, Sun LY, Bartke A. Measuring aging rates of mice subjected to caloric restriction and genetic disruption of growth hormone signaling. Aging (Albany NY). 2016; 8:539–546. PMID: 26959761.
Article
35. 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; 39:277–284. PMID: 11374913.
Article
36. 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; 72:653–660. PMID: 11336996.
Article
37. Basu A, McFarlane HG, Kopchick JJ. Spatial learning and memory in male mice with altered growth hormone action. Horm Behav. 2017; 93:18–30. PMID: 28389277.
Article
38. Rollo CD, Ko CV, Tyerman JGA, Kajiura LJ. The growth hormone axis and cognition: empirical results and integrated theory derived from giant transgenic mice. Can J Zool. 1999; 77:1874–1890.
Article
39. Gesing A, Wiesenborn D, Do A, Menon V, Schneider A, Victoria B, et al. A long-lived mouse lacking both growth hormone and growth hormone receptor: a new animal model for aging studies. J Gerontol A Biol Sci Med Sci. 2017; 72:1054–1061. PMID: 27688483.
Article
40. Holzenberger M, Dupont J, Ducos B, Leneuve P, Géloën A, Even PC, et al. IGF-1 receptor regulates lifespan and resistance to oxidative stress in mice. Nature. 2003; 421:182–187. PMID: 12483226.
Article
41. Xu J, Gontier G, Chaker Z, Lacube P, Dupont J, Holzenberger M. Longevity effect of IGF-1R(+/−) mutation depends on genetic background-specific receptor activation. Aging Cell. 2014; 13:19–28. PMID: 23898955.
42. Ashpole NM, Logan S, Yabluchanskiy A, Mitschelen MC, Yan H, Farley JA, et al. IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan. Geroscience. 2017; 39:129–145. PMID: 28409331.
Article
43. Conover CA, Bale LK. Loss of pregnancy-associated plasma protein A extends lifespan in mice. Aging Cell. 2007; 6:727–729. PMID: 17681037.
Article
44. Bale LK, West SA, Conover CA. Inducible knockdown of pregnancy-associated plasma protein-A gene expression in adult female mice extends life span. Aging Cell. 2017; 16:895–897. PMID: 28600811.
Article
45. Harrison DE, Strong R, Sharp ZD, Nelson JF, Astle CM, Flurkey K, et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009; 460:392–395. PMID: 19587680.
Article
46. 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; 1:22–29. PMID: 12882350.
Article
47. Yuan R, Tsaih SW, Petkova SB, Marin de Evsikova C, 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; 8:277–287. PMID: 19627267.
Article
48. Eklund J, Bradford GE. Longeveity and lifetime body weight in mice selected for rapid growth. Nature. 1977; 265:48–49. PMID: 834240.
49. Rollo CD. Growth negatively impacts the life span of mammals. Evol Dev. 2002; 4:55–61. PMID: 11868658.
Article
50. Greer KA, Hughes LM, Masternak MM. Connecting serum IGF-1, body size, and age in the domestic dog. Age (Dordr). 2011; 33:475–483. PMID: 20865338.
Article
51. 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:B171–B178. PMID: 9158552.
Article
52. Brosnahan MM, Paradis MR. Demographic and clinical characteristics of geriatric horses: 467 cases (1989-1999). J Am Vet Med Assoc. 2003; 223:93–98. PMID: 12839071.
Article
53. 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; 17:307–315. PMID: 15039484.
Article
54. Dhahbi J, Li X, Tran T, Masternak MM, Bartke A. Circulating blood leukocyte gene expression profiles: effects of the Ames dwarf mutation on pathways related to immunity and inflammation. Exp Gerontol. 2007; 42:772–788. PMID: 17611063.
Article
55. Stout MB, Swindell WR, Zhi X, Rohde K, List EO, Berryman DE, et al. Transcriptome profiling reveals divergent expression shifts in brown and white adipose tissue from long-lived GHRKO mice. Oncotarget. 2015; 6:26702–26715. PMID: 26436954.
Article
56. Bartke A, Wright JC, Mattison JA, Ingram DK, Miller RA, Roth GS. Extending the lifespan of long-lived mice. Nature. 2001; 414:412. PMID: 11719795.
Article
57. 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; 103:7901–7905. PMID: 16682650.
Article
58. 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; 11:73–81. PMID: 22040032.
Article
59. Darcy J, McFadden S, Fang Y, Huber JA, Zhang C, Sun LY, et al. Brown adipose tissue function is enhanced in long-lived, male ames dwarf mice. Endocrinology. 2016; 157:4744–4753. PMID: 27740871.
Article
60. 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:E1495–E1403. PMID: 29378959.
Article
61. Panici JA, Wang F, Bonkowski MS, Spong A, Bartke A, Pawlikowska L, et al. Is altered expression of hepatic insulinrelated genes in growth hormone receptor knockout mice due to GH resistance or a difference in biological life spans? J Gerontol A Biol Sci Med Sci. 2009; 64:1126–1133. PMID: 19706698.
Article
62. Wang Z, Al-Regaiey KA, Masternak MM, Bartke A. Adipocytokines and lipid levels in Ames dwarf and calorie-restricted mice. J Gerontol A Biol Sci Med Sci. 2006; 61:323–331. PMID: 16611697.
Article
63. 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; 14:1571–1580. PMID: 26876170.
Article
64. Hascup ER, Wang F, Kopchick JJ, Bartke A. Inflammatory and glutamatergic homeostasis are involved in successful aging. J Gerontol A Biol Sci Med Sci. 2016; 71:281–289. PMID: 25711529.
Article
65. Bonkowski MS, Dominici FP, Arum O, Rocha JS, Al Regaiey KA, Westbrook R, et al. Disruption of growth hormone receptor prevents calorie restriction from improving insulin action and longevity. PLoS One. 2009; 4:e4567. PMID: 19234595.
Article
66. Westbrook R, Bonkowski MS, Strader AD, Bartke A. 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; 64:443–451. PMID: 19286975.
Article
67. Sun LY, Fang Y, Patki A, Koopman JJ, Allison DB, Hill CM, et al. Longevity is impacted by growth hormone action during early postnatal period. Elife. 2017; 6:e24059. PMID: 28675141.
Article
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; 157:4502–4513. PMID: 27732088.
Article
69. Samaras TT. Human body size and the laws of scaling: physiological, performance, growth, longevity and ecological ramifications. New York: Nova Science Publishers, Inc.;2007.
70. Perkins JM, Subramanian SV, Davey Smith G, Özaltin E. Adult height, nutrition, and population health. Nutr Rev. 2016; 74:149–165. PMID: 26928678.
Article
71. 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:e94385. PMID: 24804734.
Article
72. Bonafè M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C, 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. PMID: 12843179.
Article
73. van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ, et al. Reduced insulin/IGF-1 signalling and human longevity. Aging Cell. 2005; 4:79–85. PMID: 15771611.
Article
74. 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; 105:3438–3442. PMID: 18316725.
Article
75. Krzisnik C, Kolacio Z, Battelino T, Brown M, Parks JS, Laron Z. The “little people” of the island of Krk - revisited. Etiology of hypopituitarism revealed. J Endocr Genet. 1999; 1:9–19.
Article
76. Laron Z, Kauli R, Lapkina L, Werner H. IGF-I deficiency, longevity and cancer protection of patients with Laron syndrome. Mutat Res Rev Mutat Res. 2017; 772:123–133. PMID: 28528685.
Article
77. Aguiar-Oliveira MH, Souza AHO, Oliveira CRP, Campos VC, Oliveira-Neto LA, Salvatori R. The multiple facets of GHRH/ GH/IGF-I axis: lessons from lifetime, untreated, isolated GH deficiency due to a GHRH receptor gene mutation. Eur J Endocrinol. 2017; 177:R85–R97. PMID: 28428227.
78. Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, 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.
Article
79. 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; 88:3664–3667. PMID: 12915652.
Article
80. Jadresic A, Banks LM, Child DF, Diamant L, Doyle FH, Fraser TR, et al. The acromegaly syndrome. Relation between clinical features, growth hormone values and radiological characteristics of the pituitary tumours. Q J Med. 1982; 51:189–204. PMID: 7111679.
81. Orme SM, McNally RJ, Cartwright RA, Belchetz PE. Mortality and cancer incidence in acromegaly: a retrospective cohort study. United Kingdom Acromegaly Study Group. J Clin Endocrinol Metab. 1998; 83:2730–2734. PMID: 9709939.
82. Chahal HS, Stals K, Unterländer M, Balding DJ, Thomas MG, Kumar AV, et al. AIP mutation in pituitary adenomas in the 18th century and today. N Engl J Med. 2011; 364:43–50. PMID: 21208107.
83. Ramírez-Rentería C, Hernández-Ramírez LC, Portocarrero-Ortiz L, Vargas G, Melgar V, Espinosa E, et al. AIP mutations in young patients with acromegaly and the Tampico Giant: the Mexican experience. Endocrine. 2016; 53:402–411. PMID: 27033541.
Article
84. Bartke A. Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice. Neuroendocrinology. 2003; 78:210–216. PMID: 14583653.
Article
85. 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; DOI: 10.1111/acel.12519.
Article
86. 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; 13:769–771. PMID: 24618355.
Article
87. Ben-Avraham D, Govindaraju DR, Budagov T, Fradin D, Durda P, Liu B, et al. The GH receptor exon 3 deletion is a marker of male-specific exceptional longevity associated with increased GH sensitivity and taller stature. Sci Adv. 2017; 3:e1602025. PMID: 28630896.
Article
88. Tanisawa K, Hirose N, Arai Y, Shimokata H, Yamada Y, Kawai H, et al. Inverse association between height-increasing alleles and extreme longevity in Japanese women. J Gerontol A Biol Sci Med Sci. 2017; DOI: 10.1093/gerona/glx155.
Article
89. Laron Z. The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency. Hormones (Athens). 2008; 7:24–27. PMID: 18359741.
Article
90. Guevara-Aguirre J, Rosenbloom AL, Balasubramanian P, Teran E, Guevara-Aguirre M, Guevara C, et al. GH Receptor deficiency in ecuadorian adults is associated with obesity and enhanced insulin sensitivity. J Clin Endocrinol Metab. 2015; 100:2589–2596. PMID: 25985182.
Article
91. Nashiro K, Guevara-Aguirre J, Braskie MN, Hafzalla GW, Velasco R, Balasubramanian P, et al. Brain structure and function associated with younger adults in growth hormone receptor-deficient humans. J Neurosci. 2017; 37:1696–1707. PMID: 28073935.
Article
92. Gordon CJ. Thermal physiology of laboratory mice: defining thermoneutrality. J Therm Biol. 2012; 37:654–685.
Article
93. Westbrook R. The effects of altered growth hormone signaling on murine metabolism. Carbondale (IL): Southern Illinois University;2012.
94. Karp CL. Unstressing intemperate models: how cold stress undermines mouse modeling. J Exp Med. 2012; 209:1069–1074. PMID: 22665703.
Article
95. Maloney SK, Fuller A, Mitchell D, Gordon C, Overton JM. Translating animal model research: does it matter that our rodents are cold? Physiology (Bethesda). 2014; 29:413–420. PMID: 25362635.
Article
96. Sonntag WE, Carter CS, Ikeno Y, Ekenstedt K, Carlson CS, Loeser RF, et al. Adult-onset growth hormone and insulinlike growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span. Endocrinology. 2005; 146:2920–2932. PMID: 15790724.
Article
97. 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; 18:57. PMID: 28351423.
Article
98. 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; 18:58. PMID: 28351383.
Article
99. Williams GC. Pleiotropy, natural selection, and the evolution of senescence. Evolution. 1957; 11:398–411.
Article
Full Text Links
  • WJMH
Actions
Cited
CITED
export Copy
Close
Share
  • Twitter
  • Facebook
Similar articles
Copyright © 2024 by Korean Association of Medical Journal Editors. All rights reserved.     E-mail: koreamed@kamje.or.kr