Early Life Programming of Aging in Genetically Long-Lived Mice

  • Andrzej BartkeEmail author
  • Liou Sun
Part of the Healthy Ageing and Longevity book series (HAL, volume 9)


Mammalian aging and longevity are related to growth hormone (GH) actions and GH-dependent traits including growth, maturation and adult body size. In laboratory stocks of mice, genetic GH deficiency or resistance led to remarkable extension of healthspan and longevity. In GH-deficient Ames dwarf mice a brief period of GH replacement therapy normalizes (“rescues”) many adult aging-related traits and shortens longevity. This indicates that absence of GH signals during the period of rapid pre- and early post-weaning growth importantly contributes to slow and healthy aging of these long-lived mutants. More work is needed to define the role of GH at different stages of life history in the control of aging.


Developmental programming Trajectory of aging Longevity Growth hormone signaling Healthspan 


  1. Aguiar-Oliveira MH, Bartke A (2018) Growth hormone deficiency: health and longevity. Endocr RevGoogle Scholar
  2. Aguiar-Oliveira MH, Souza AHO, Oliveira CRP, Campos VC, Oliveira-Neto LA, Salvatori R (2017) Mechanisms in endocrinology: 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 177(2):R85–R97. Scholar
  3. Aguiar-Oliveira MH, Davalos C, Campos VC, Oliveira Neto LA, Marinho CG, Oliveira CRP (2018) Hypothalamic abnormalities: growth failure due to defects of the GHRH receptor. Growth Horm IGF Res 38:14–18. Scholar
  4. Amador-Noguez D, Yagi K, Venable S, Darlington G (2004) Gene expression profile of long-lived Ames dwarf mice and Little mice. Aging Cell 3(6):423–441. Scholar
  5. Anisimov VN, Popovich IG, Zabezhinski MA, Egormin PA, Yurova MN, Semenchenko AV, Tyndyk ML, Panchenko AV, Trashkov AP, Vasiliev AG, Khaitsev NV (2015) Sex differences in aging, life span and spontaneous tumorigenesis in 129/Sv mice neonatally exposed to metformin. Cell Cycle 14(1):46–55. Scholar
  6. Ashpole NM, Logan S, Yabluchanskiy A, Mitschelen MC, Yan H, Farley JA, Hodges EL, Ungvari Z, Csiszar A, Chen S, Georgescu C, Hubbard GB, Ikeno Y, Sonntag WE (2017) IGF-1 has sexually dimorphic, pleiotropic, and time-dependent effects on healthspan, pathology, and lifespan. Geroscience 39(2):129–145. Scholar
  7. Bartke A (1964) Histology of the anterior hypophysis, thyroid and gonads of two types of dwarf mice. Anat Rec 149(2):225–235. Scholar
  8. Bartke A (1965) The response of two types of dwarf mice to growth hormone, thyrotropin, and thyroxine. Gen Comp Endocr 5:418–426CrossRefGoogle Scholar
  9. Bartke A (1966) Reproduction of female dwarf mice treated with prolactin. J Reprod Fertil 11(2):203–206CrossRefGoogle Scholar
  10. Bartke A (1968) The response of dwarf mice to murine thyroid-stimulating hormone. Gen Comp Endocrinol 11(1):246–247CrossRefGoogle Scholar
  11. Bartke A (1973) Differential requirement for prolactin during pregnancy in the mouse. Biol Reprod 9(4):379–383CrossRefGoogle Scholar
  12. Bartke A (2003) Can growth hormone (GH) accelerate aging? Evidence from GH-transgenic mice. Neuroendocrinology 78(4):210–216. Scholar
  13. Bartke A (2011) Single-gene mutations and healthy ageing in mammals. Philos Trans R Soc B 366(1561):28–34. Scholar
  14. Bartke A, Coschigano K, Kopchick J, Chandrashekar V, Mattison J, Kinney B, Hauck S (2001) Genes that prolong life: relationships of growth hormone and growth to aging and life span. J Gerontol A Biol Sci Med Sci 56(8):B340–349CrossRefGoogle Scholar
  15. Bartke A, Sun LY, Longo V (2013) Somatotropic signaling: trade-offs between growth, reproductive development, and longevity. Physiol Rev 93(2):571–598. Scholar
  16. Basu R, Qian Y, Kopchick JJ (2018) Mechanisms in endocrinology: Lessons from growth hormone receptor gene-disrupted mice: are there benefits of endocrine defects? Eur J Endocrinol 178(5):R155–R181. Scholar
  17. Berryman DE, List EO, Coschigano KT, Behar K, Kim JK, Kopchick JJ (2004) Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Horm IGF Res 14(4):309–318. Scholar
  18. Bokov AF, Lindsey ML, Khodr C, Sabia MR, Richardson A (2009) Long-lived Ames dwarf mice are resistant to chemical stressors. J Gerontol A Biol Sci Med Sci 64(8):819–827. Scholar
  19. Borg KE, Brown-Borg HM, Bartke A (1995) Assessment of the primary adrenal cortical and pancreatic hormone basal levels in relation to plasma glucose and age in the unstressed Ames dwarf mouse. Proc Soc Exp Biol Med 210(2):126–133CrossRefGoogle Scholar
  20. Boylston WH, Gerstner A, DeFord JH, Madsen M, Flurkey K, Harrison DE, Papaconstantinou J (2004) Altered cholesterologenic and lipogenic transcriptional profile in livers of aging Snell dwarf (Pit1dw/dwJ) mice. Aging Cell 3(5):283–296. Scholar
  21. Brosnahan MM, Paradis MR (2003) Demographic and clinical characteristics of geriatric horses: 467 cases (1989–1999). J Am Vet Med Assoc 223(1):93–98CrossRefGoogle Scholar
  22. Brown-Borg HM (2007) Hormonal regulation of longevity in mammals. Ageing Res Rev 6(1):28–45. Scholar
  23. Brown-Borg HM (2015) The somatotropic axis and longevity in mice. Am J Physiol Endocrinol Metab 309(6):E503–510. Scholar
  24. Brown-Borg HM, Borg KE, Meliska CJ, Bartke A (1996) Dwarf mice and the ageing process. Nature 384(6604):33. Scholar
  25. Brown-Borg HM, Rakoczy SG, Romanick MA, Kennedy MA (2002) Effects of growth hormone and insulin-like growth factor-1 on hepatocyte antioxidative enzymes. Exp Biol Med (Maywood) 227(2):94–104CrossRefGoogle Scholar
  26. Brown-Borg HM, Johnson WT, Rakoczy SG (2012) Expression of oxidative phosphorylation components in mitochondria of long-living Ames dwarf mice. Age (Dordr) 34(1):43–57. Scholar
  27. Chandrashekar V, Bartke A (1993) Induction of endogenous insulin-like growth factor-I secretion alters the hypothalamic-pituitary-testicular function in growth hormone-deficient adult dwarf mice. Biol Reprod 48(3):544–551CrossRefGoogle Scholar
  28. Colao A, Ferone D, Marzullo P, Lombardi G (2004) Systemic complications of acromegaly: epidemiology, pathogenesis, and management. Endocr Rev 25(1):102–152. Scholar
  29. Coschigano KT, Holland AN, Riders ME, List EO, Flyvbjerg A, 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(9):3799–3810CrossRefGoogle Scholar
  30. Costa UM, Oliveira CR, Salvatori R, Barreto-Filho JA, Campos VC, Oliveira FT, Rocha IE, Oliveira JL, Silva WA, Aguiar-Oliveira MH (2016) Brazilian adult individuals with untreated isolated GH deficiency do not have accelerated subclinical atherosclerosis. Endocr Connect 5(1):41–46. Scholar
  31. Darcy J, Fang Y, Hill CM, McFadden S, Sun LY, Bartke A (2016a) Metabolic alterations from early life thyroxine replacement therapy in male Ames dwarf mice are transient. Exp Biol Med (Maywood). Scholar
  32. Darcy J, McFadden S, Fang Y, Huber JA, Zhang C, Sun LY, Bartke A (2016b) Brown adipose tissue function is enhanced in long-lived, male Ames dwarf mice. Endocrinology 157(12):4744–4753. Scholar
  33. Dato S, Soerensen M, De Rango F, Rose G, Christensen K, Christiansen L, Passarino G (2018) The genetic component of human longevity: new insights from the analysis of pathway-based SNP-SNP interactions. Aging Cell 17(3):e12755. Scholar
  34. Dominici FP, Hauck S, Argentino DP, Bartke A, Turyn D (2002) Increased insulin sensitivity and upregulation of insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2 in liver of Ames dwarf mice. J Endocrinol 173(1):81–94CrossRefGoogle Scholar
  35. Elftman H, Wegelius O (1959) Anterior pituitary cytology of the dwarf mouse. Anat Rec 135:43–49CrossRefGoogle Scholar
  36. Fang Y, Hill CM, Darcy J, Reyes-Ordonez A, Arauz E, McFadden S, Zhang C, Osland J, Gao J, Zhang T, Frank SJ, Javors MA, Yuan R, Kopchick JJ, Sun LY, Chen J, Bartke A (2018) Effects of rapamycin on growth hormone receptor knockout mice. Proc Natl Acad Sci USA 115(7):E1495–E1503. Scholar
  37. Finkel T, Holbrook NJ (2000) Oxidants, oxidative stress and the biology of ageing. Nature 408(6809):239–247. Scholar
  38. Flachsbart F, Caliebe A, Kleindorp R, Blanche H, von Eller-Eberstein H, Nikolaus S, Schreiber S, Nebel A (2009) Association of FOXO3A variation with human longevity confirmed in German centenarians. Proc Natl Acad Sci USA 106(8):2700–2705. Scholar
  39. Flurkey K, Papaconstantinou J, Miller RA, Harrison DE (2001) Lifespan extension and delayed immune and collagen aging in mutant mice with defects in growth hormone production. Proc Natl Acad Sci USA 98(12):6736–6741. 111158898 [pii]CrossRefGoogle Scholar
  40. Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–9. Scholar
  41. Garcia AM, Busuttil RA, Calder RB, Dolle ME, Diaz V, McMahan CA, Bartke A, Nelson J, Reddick R, Vijg J (2008) Effect of Ames dwarfism and caloric restriction on spontaneous DNA mutation frequency in different mouse tissues. Mech Ageing Dev 129(9):528–533. Scholar
  42. Greer KA, Canterberry SC, Murphy KE (2007) Statistical analysis regarding the effects of height and weight on life span of the domestic dog. Res Vet Sci 82(2):208–214. Scholar
  43. Guevara-Aguirre J, Balasubramanian P, Guevara-Aguirre M, Wei M, Madia F, Cheng CW, Hwang D, Martin-Montalvo A, Saavedra J, Ingles S, de Cabo R, Cohen P, Longo VD (2011) Growth hormone receptor deficiency is associated with a major reduction in pro-aging signaling, cancer, and diabetes in humans. Sci Transl Med 3(70):70ra13. Scholar
  44. Guevara-Aguirre J, Rosenbloom AL, Balasubramanian P, Teran E, Guevara-Aguirre M, Guevara C, Procel P, Alfaras I, De Cabo R, Di Biase S, Narvaez L, Saavedra J, Longo VD (2015) GH receptor deficiency in ecuadorian adults is associated with obesity and enhanced insulin sensitivity. J Clin Endocrinol Metab 100(7):2589–2596. Scholar
  45. Hascup ER, Wang F, Kopchick JJ, Bartke A (2016) Inflammatory and glutamatergic homeostasis are involved in successful aging. J Gerontol A Biol Sci Med Sci 71(3):281–289. Scholar
  46. He Q, Morris BJ, Grove JS, Petrovitch H, Ross W, Masaki KH, Rodriguez B, Chen R, Donlon TA, Willcox DC, Willcox BJ (2014) Shorter men live longer: association of height with longevity and FOXO3 genotype in American men of Japanese ancestry. PLoS ONE 9(5):e94385. Scholar
  47. Hill CM, Fang Y, Miquet JG, Sun LY, Masternak MM, Bartke A (2016) Long-lived hypopituitary Ames dwarf mice are resistant to the detrimental effects of high-fat diet on metabolic function and energy expenditure. Aging Cell 15(3):509–521. Scholar
  48. Hine C, Kim HJ, Zhu Y, Harputlugil E, Longchamp A, Matos MS, Ramadoss P, Bauerle K, Brace L, Asara JM, Ozaki CK, Cheng SY, Singha S, Ahn KH, Kimmelman A, Fisher FM, Pissios P, Withers DJ, Selman C, Wang R, Yen K, Longo VD, Cohen P, Bartke A, Kopchick JJ, Miller R, Hollenberg AN, Mitchell JR (2017) Hypothalamic-pituitary axis regulates hydrogen sulfide production. Cell Metab 25(6):1320–1333 e1325. Scholar
  49. Holdaway IM, Rajasoorya RC, Gamble GD (2004) Factors influencing mortality in acromegaly. J Clin Endocrinol Metab 89(2):667–674. Scholar
  50. Ikeno Y, Bronson RT, Hubbard GB, Lee S, Bartke A (2003) Delayed occurrence of fatal neoplastic diseases in Ames dwarf mice: correlation to extended longevity. J Gerontol A Biol Sci Med Sci 58(4):291–296CrossRefGoogle Scholar
  51. Ikeno Y, Hubbard GB, Lee S, Cortez LA, Lew CM, Webb CR, Berryman DE, List EO, Kopchick JJ, Bartke A (2009) Reduced incidence and delayed occurrence of fatal neoplastic diseases in growth hormone receptor/binding protein knockout mice. J Gerontol A Biol Sci Med Sci 64(5):522–529. Scholar
  52. Junnila RK, Duran-Ortiz S, Suer O, Sustarsic EG, Berryman DE, List EO, Kopchick JJ (2016) Disruption of the GH receptor gene in adult mice increases maximal lifespan in females. Endocrinology 157(12):4502–4513. Scholar
  53. Kinney BA, Meliska CJ, Steger RW, Bartke A (2001) Evidence that Ames dwarf mice age differently from their normal siblings in behavioral and learning and memory parameters. Horm Behav 39(4):277–284. Scholar
  54. Kucia M, Shin DM, Liu R, Ratajczak J, Bryndza E, Masternak MM, Bartke A, Ratajczak MZ (2011) Reduced number of VSELs in the bone marrow of growth hormone transgenic mice indicates that chronically elevated Igf1 level accelerates age-dependent exhaustion of pluripotent stem cell pool: a novel view on aging. Leukemia 25(8):1370–1374. Scholar
  55. Laron Z (2008) The GH-IGF1 axis and longevity. The paradigm of IGF1 deficiency. Hormones (Athens) 7(1):24–27CrossRefGoogle Scholar
  56. Lewin N, Swanson EM, Williams BL, Holekamp KE (2017) Juvenile concentrations of IGF-1 predict life-history trade-offs in a wild mammal. Funct Ecol 31(4):894–902. Scholar
  57. Louis A, Bartke A, Masternak MM (2010) Effects of growth hormone and thyroxine replacement therapy on insulin signaling in Ames dwarf mice. J Gerontol A Biol Sci Med Sci 65(4):344–352. Scholar
  58. MacRae SL, Zhang Q, Lemetre C, Seim I, Calder RB, Hoeijmakers J, Suh Y, Gladyshev VN, Seluanov A, Gorbunova V, Vijg J, Zhang ZD (2015) Comparative analysis of genome maintenance genes in naked mole rat, mouse, and human. Aging Cell 14(2):288–291. Scholar
  59. Masternak MM, Bartke A, Wang F, Spong A, Gesing A, Fang Y, Salmon AB, Hughes LF, Liberati T, Boparai R, Kopchick JJ, Westbrook R (2012) Metabolic effects of intra-abdominal fat in GHRKO mice. Aging Cell 11(1):73–81. Scholar
  60. Menon V, Zhi X, Hossain T, Bartke A, Spong A, Gesing A, Masternak MM (2014) The contribution of visceral fat to improved insulin signaling in Ames dwarf mice. Aging Cell 13(3):497–506. Scholar
  61. Milholland B, Dong X, Zhang L, Hao X, Suh Y, Vijg J (2017) Differences between germline and somatic mutation rates in humans and mice. Nat Commun 8:15183. Scholar
  62. Miller RA, Harper JM, Galecki A, Burke DT (2002) Big mice die young: early life body weight predicts longevity in genetically heterogeneous mice. Aging Cell 1(1):22–29CrossRefGoogle Scholar
  63. Panici JA, Harper JM, Miller RA, Bartke A, Spong A, Masternak MM (2010) Early life growth hormone treatment shortens longevity and decreases cellular stress resistance in long-lived mutant mice. FASEB J 24(12):5073–5079. Scholar
  64. Patronek GJ, Waters DJ, Glickman LT (1997) Comparative longevity of pet dogs and humans: implications for gerontology research. J Gerontol A Biol Sci Med Sci 52(3):B171–178CrossRefGoogle Scholar
  65. Pendergrass WR, Li Y, Jiang D, Wolf NS (1993) Decrease in cellular replicative potential in “giant” mice transfected with the bovine growth hormone gene correlates to shortened life span. J Cell Physiol 156(1):96–103. Scholar
  66. Perez VI, Bokov A, Van Remmen H, Mele J, Ran Q, Ikeno Y, Richardson A (2009) Is the oxidative stress theory of aging dead? Biochim Biophys Acta 1790(10):1005–1014. Scholar
  67. Podlutsky A, Valcarcel-Ares MN, Yancey K, Podlutskaya V, Nagykaldi E, Gautam T, Miller RA, Sonntag WE, Csiszar A, Ungvari Z (2017) 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 39(2):147–160. Scholar
  68. Ricklefs RE, Wikelski M (2002) The physiology/life-history nexus. Trends Ecol Evol 17(10):462–468. Scholar
  69. Rollo CD (2002) Growth negatively impacts the life span of mammals. Evol Dev 4(1):55–61CrossRefGoogle Scholar
  70. Sadagurski M, Landeryou T, Cady G, Kopchick JJ, List EO, Berryman DE, Bartke A, Miller RA (2015) Growth hormone modulates hypothalamic inflammation in long-lived pituitary dwarf mice. Aging Cell 14(6):1045–1054. Scholar
  71. Salmon AB, Murakami S, Bartke A, Kopchick J, Yasumura K, Miller RA (2005) Fibroblast cell lines from young adult mice of long-lived mutant strains are resistant to multiple forms of stress. Am J Physiol Endocrinol Metab 289(1):E23–29. Scholar
  72. Salzman TC, McLaughlin AL, Westneat DF, Crowley PH (2018) Energetic trade-offs and feedbacks between behavior and metabolism influence correlations between pace-of-life attributes. Behav Ecol Sociobiol 72(3):54. Scholar
  73. Samaras TT (2007) Human body size and the laws of scaling: physiological, performance, growth, longevity and ecological ramifications. Nova Science Publishers Inc, New YorkGoogle Scholar
  74. Sanz A, Bartke A, Barja G (2002) Long-lived Ames dwarf mice: oxidative damage to mitochondrial DNA in heart and brain. J Am Aging Assoc 25:119–122PubMedPubMedCentralGoogle Scholar
  75. Sharp ZD, Strong R (2010) The role of mTOR signaling in controlling mammalian life span: what a fungicide teaches us about longevity. J Gerontol A Biol Sci Med Sci 65(6):580–589. Scholar
  76. Shore DE, Ruvkun G (2013) A cytoprotective perspective on longevity regulation. Trends Cell Biol 23(9):409–420. Scholar
  77. Snell GD (1929a) Dwarf, a new mendelian recessive character of the house mouse. Proc Natl Acad Sci USA 15(9):733–734CrossRefGoogle Scholar
  78. Snell GD (1929b) An inherent defect in the theory that growth rate is controlled by an autocatalytic process. Proc Natl Acad Sci USA 15(3):274–281CrossRefGoogle Scholar
  79. Sonntag WE, Carter CS, Ikeno Y, Ekenstedt K, Carlson CS, Loeser RF, Chakrabarty S, Lee S, Bennett C, Ingram R, Moore T, Ramsey M (2005) Adult-onset growth hormone and insulin-like growth factor I deficiency reduces neoplastic disease, modifies age-related pathology, and increases life span. Endocrinology 146(7):2920–2932. Scholar
  80. Sornson MW, Wu W, Dasen JS, Flynn SE, Norman DJ, O’Connell SM, Gukovsky I, Carriere C, Ryan AK, Miller AP, Zuo L, Gleiberman AS, Andersen B, Beamer WG, Rosenfeld MG (1996) Pituitary lineage determination by the Prophet of Pit-1 homeodomain factor defective in Ames dwarfism. Nature 384(6607):327–333. Scholar
  81. Spadaro O, Goldberg EL, Camell CD, Youm YH, Kopchick JJ, Nguyen KY, Bartke A, Sun LY, Dixit VD (2016) Growth hormone receptor deficiency protects against age-related NLRP3 inflammasome activation and immune senescence. Cell Rep 14(7):1571–1580. Scholar
  82. Stout MB, Tchkonia T, Pirtskhalava T, Palmer AK, List EO, Berryman DE, Lubbers ER, Escande C, Spong A, Masternak MM, Oberg AL, LeBrasseur NK, Miller RA, Kopchick JJ, Bartke A, Kirkland JL (2014) Growth hormone action predicts age-related white adipose tissue dysfunction and senescent cell burden in mice. Aging (Albany NY) 6(7):575–586CrossRefGoogle Scholar
  83. Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ, Barzilai N, Cohen P (2008) Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 105(9):3438–3442. Scholar
  84. Sun LY, Spong A, Swindell WR, Fang Y, Hill C, Huber JA, Boehm JD, Westbrook R, Salvatori R, Bartke A (2013) Growth hormone-releasing hormone disruption extends lifespan and regulates response to caloric restriction in mice. Elife 2:e01098. Scholar
  85. Sun LY, Fang Y, Patki A, Koopman JJ, Allison DB, Hill CM, Masternak MM, Darcy J, Wang J, McFadden S, Bartke A (2017) Longevity is impacted by growth hormone action during early postnatal period. Elife 6.
  86. van der Spoel E, Jansen SW, Akintola AA, Ballieux BE, Cobbaert CM, Slagboom PE, Blauw GJ, Westendorp RG, Pijl H, Roelfsema F, van Heemst D (2016) Growth hormone secretion is diminished and tightly controlled in humans enriched for familial longevity. Aging Cell. Scholar
  87. Vergara M, Smith-Wheelock M, Harper JM, Sigler R, Miller RA (2004) Hormone-treated Snell dwarf mice regain fertility but remain long lived and disease resistant. J Gerontol A Biol Sci Med Sci 59(12):1244–1250CrossRefGoogle Scholar
  88. Wang Z, Al-Regaiey KA, Masternak MM, Bartke A (2006) Adipocytokines and lipid levels in Ames dwarf and calorie-restricted mice. J Gerontol A Biol Sci Med Sci 61(4):323–331CrossRefGoogle Scholar
  89. Westbrook R, Bonkowski MS, Strader AD, Bartke A (2009) 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 64(4):443–451. Scholar
  90. Wiesenborn DS, Ayala JE, King E, Masternak MM (2014) Insulin sensitivity in long-living Ames dwarf mice. Age (Dordr) 36(5):9709. Scholar
  91. Wirth-Dzieciolowska E, Czuminska K (2000) Longevity and aging of mice from lines divergently selected for body weight for over 90 generations. Biogerontology 1(2):171–178CrossRefGoogle Scholar
  92. Wolf E, Kahnt E, Ehrlein J, Hermanns W, Brem G, Wanke R (1993) Effects of long-term elevated serum levels of growth hormone on life expectancy of mice: lessons from transgenic animal models. Mech Ageing Dev 68(1–3):71–87CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Department of Internal MedicineSouthern Illinois University School of MedicineSpringfieldUSA
  2. 2.Department of BiologyUniversity of Alabama at BirminghamBirminghamUSA

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