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. 2000 Nov;197(Pt 4):575–585. doi: 10.1046/j.1469-7580.2000.19740575.x

The effects of growth hormone and IGF-1 deficiency on cerebrovascular and brain ageing

WILLIAM E SONNTAG 1,✉, COLLEEN LYNCH 1, PHILLIP THORNTON 1, AMIR KHAN 1, SEAN BENNETT 1, RHONDA INGRAM 1
PMCID: PMC1468173  PMID: 11197531

Abstract

Research studies clearly indicate that age-related changes in cellular and tissue function are linked to decreases in the anabolic hormones, growth hormone and insulin-like growth factor (IGF)-1. Although there has been extensive research on the effects of these hormones on bone and muscle mass, their effect on cerebrovascular and brain ageing has received little attention. We have also observed that in response to moderate calorie restriction (a treatment that increases mean and maximal lifespan by 30–40%), age-related decreases in growth hormone secretion are ameliorated (despite a decline in plasma levels of IGF-1) suggesting that some of the effects of calorie restriction are mediated by modifying the regulation of the growth hormone/IGF-1 axis. Recently, we have observed that microvascular density on the surface of the brain decreases with age and that these vascular changes are ameliorated by moderate calorie restriction. Analysis of cerebral blood flow paralleled the changes in vasculature in both groups. Administration of growth hormone for 28 d was also found to increase microvascular density in aged animals and further analysis indicated that the cerebral vasculature is an important paracrine source of IGF-1 for the brain. In subsequent studies, administration of GHRH (to increase endogenous release of growth hormone) or direct administration of IGF-1 was shown to reverse the age-related decline in spatial working and reference memory. Similarly, antagonism of IGF-1 action in the brains of young animals impaired both learning and reference memory. Investigation of the mechanisms of action of IGF-1 suggested that this hormone regulates age-related alterations in NMDA receptor subtypes (e.g. NMDAR2A and R2B). The beneficial role of growth hormone and IGF-1 in ameliorating vascular and brain ageing are counterbalanced by their well-recognised roles in age-related pathogenesis. Although research in this area is still evolving, our results suggest that decreases in growth hormone and IGF-1 with age have both beneficial and deleterious effects. Furthermore, part of the actions of moderate calorie restriction on tissue function and lifespan may be mediated through alterations in the growth hormone/IGF-1 axis.

Keywords: Ageing, cerebral vasculature, growth hormone, insulin-like growth factor-1

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Selected References

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  1. Alberch J., Pérez-Navarro E., Arenas E., Marsal J. Involvement of nerve growth factor and its receptor in the regulation of the cholinergic function in aged rats. J Neurochem. 1991 Nov;57(5):1483–1487. doi: 10.1111/j.1471-4159.1991.tb06342.x. [DOI] [PubMed] [Google Scholar]
  2. Ankrapp D. P., Bevan D. R. Insulin-like growth factor-I and human lung fibroblast-derived insulin-like growth factor-I stimulate the proliferation of human lung carcinoma cells in vitro. Cancer Res. 1993 Jul 15;53(14):3399–3404. [PubMed] [Google Scholar]
  3. Arnsten A. F., Goldman-Rakic P. S. Alpha 2-adrenergic mechanisms in prefrontal cortex associated with cognitive decline in aged nonhuman primates. Science. 1985 Dec 13;230(4731):1273–1276. doi: 10.1126/science.2999977. [DOI] [PubMed] [Google Scholar]
  4. Arteaga C. L., Osborne C. K. Growth inhibition of human breast cancer cells in vitro with an antibody against the type I somatomedin receptor. Cancer Res. 1989 Nov 15;49(22):6237–6241. [PubMed] [Google Scholar]
  5. Barnes C. A. Memory deficits associated with senescence: a neurophysiological and behavioral study in the rat. J Comp Physiol Psychol. 1979 Feb;93(1):74–104. doi: 10.1037/h0077579. [DOI] [PubMed] [Google Scholar]
  6. Barnes C. A., Nadel L., Honig W. K. Spatial memory deficit in senescent rats. Can J Psychol. 1980 Mar;34(1):29–39. doi: 10.1037/h0081022. [DOI] [PubMed] [Google Scholar]
  7. Bartke A., Cecim M., Tang K., Steger R. W., Chandrashekar V., Turyn D. Neuroendocrine and reproductive consequences of overexpression of growth hormone in transgenic mice. Proc Soc Exp Biol Med. 1994 Sep;206(4):345–359. doi: 10.3181/00379727-206-43771. [DOI] [PubMed] [Google Scholar]
  8. Bengtsson B. A., Edén S., Lönn L., Kvist H., Stokland A., Lindstedt G., Bosaeus I., Tölli J., Sjöström L., Isaksson O. G. Treatment of adults with growth hormone (GH) deficiency with recombinant human GH. J Clin Endocrinol Metab. 1993 Feb;76(2):309–317. doi: 10.1210/jcem.76.2.8432773. [DOI] [PubMed] [Google Scholar]
  9. Björk S., Jönsson B., Westphal O., Levin J. E. Quality of life of adults with growth hormone deficiency: a controlled study. Acta Paediatr Scand Suppl. 1989;356:55-9; discussion 60, 73-4. doi: 10.1111/j.1651-2227.1989.tb11242.x. [DOI] [PubMed] [Google Scholar]
  10. Bondy C. A. Transient IGF-I gene expression during the maturation of functionally related central projection neurons. J Neurosci. 1991 Nov;11(11):3442–3455. doi: 10.1523/JNEUROSCI.11-11-03442.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Bronson R. T., Lipman R. D. Reduction in rate of occurrence of age related lesions in dietary restricted laboratory mice. Growth Dev Aging. 1991 Fall;55(3):169–184. [PubMed] [Google Scholar]
  12. Brown-Borg H. M., Borg K. E., Meliska C. J., Bartke A. Dwarf mice and the ageing process. Nature. 1996 Nov 7;384(6604):33–33. doi: 10.1038/384033a0. [DOI] [PubMed] [Google Scholar]
  13. Burke D. M., Light L. L. Memory and aging: the role of retrieval processes. Psychol Bull. 1981 Nov;90(3):513–514. [PubMed] [Google Scholar]
  14. Chen K. S., Masliah E., Mallory M., Gage F. H. Synaptic loss in cognitively impaired aged rats is ameliorated by chronic human nerve growth factor infusion. Neuroscience. 1995 Sep;68(1):19–27. doi: 10.1016/0306-4522(95)00099-5. [DOI] [PubMed] [Google Scholar]
  15. Corpas E., Harman S. M., Blackman M. R. Human growth hormone and human aging. Endocr Rev. 1993 Feb;14(1):20–39. doi: 10.1210/edrv-14-1-20. [DOI] [PubMed] [Google Scholar]
  16. D'Costa A. P., Xu X., Ingram R. L., Sonntag W. E. Insulin-like growth factor-1 stimulation of protein synthesis is attenuated in cerebral cortex of aging rats. Neuroscience. 1995 Apr;65(3):805–813. doi: 10.1016/0306-4522(94)00495-q. [DOI] [PubMed] [Google Scholar]
  17. D'Ercole A. J., Ye P., Calikoglu A. S., Gutierrez-Ospina G. The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol. 1996 Dec;13(3):227–255. doi: 10.1007/BF02740625. [DOI] [PubMed] [Google Scholar]
  18. Delafontaine P., Bernstein K. E., Alexander R. W. Insulin-like growth factor I gene expression in vascular cells. Hypertension. 1991 May;17(5):693–699. doi: 10.1161/01.hyp.17.5.693. [DOI] [PubMed] [Google Scholar]
  19. Delafontaine P. Insulin-like growth factor I and its binding proteins in the cardiovascular system. Cardiovasc Res. 1995 Dec;30(6):825–834. [PubMed] [Google Scholar]
  20. Delafontaine P., Lou H., Alexander R. W. Regulation of insulin-like growth factor I messenger RNA levels in vascular smooth muscle cells. Hypertension. 1991 Dec;18(6):742–747. doi: 10.1161/01.hyp.18.6.742. [DOI] [PubMed] [Google Scholar]
  21. El-Badry O. M., Romanus J. A., Helman L. J., Cooper M. J., Rechler M. M., Israel M. A. Autonomous growth of a human neuroblastoma cell line is mediated by insulin-like growth factor II. J Clin Invest. 1989 Sep;84(3):829–839. doi: 10.1172/JCI114243. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Fischer W. Nerve growth factor reverses spatial memory impairments in aged rats. Neurochem Int. 1994 Jul;25(1):47–52. doi: 10.1016/0197-0186(94)90052-3. [DOI] [PubMed] [Google Scholar]
  23. Fischer W., Sirevaag A., Wiegand S. J., Lindsay R. M., Björklund A. Reversal of spatial memory impairments in aged rats by nerve growth factor and neurotrophins 3 and 4/5 but not by brain-derived neurotrophic factor. Proc Natl Acad Sci U S A. 1994 Aug 30;91(18):8607–8611. doi: 10.1073/pnas.91.18.8607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Florini J. R., Harned J. A., Richman R. A., Weiss J. P. Effect of rat age on serum levels of growth hormone and somatomedins. Mech Ageing Dev. 1981 Feb;15(2):165–176. doi: 10.1016/0047-6374(81)90072-5. [DOI] [PubMed] [Google Scholar]
  25. Folkow B., Isaksson O. P., Karlström G., Lever A. F., Nordlander M. The importance of hypophyseal hormones for structural cardiovascular adaptation in hypertension. J Hypertens Suppl. 1988 Dec;6(4):S166–S169. doi: 10.1097/00004872-198812040-00049. [DOI] [PubMed] [Google Scholar]
  26. Foster J. A., Rich C. B., Miller M., Benedict M. R., Richman R. A., Florini J. R. Effect of age and IGF-I administration on elastin gene expression in rat aorta. J Gerontol. 1990 Jul;45(4):B113–B118. doi: 10.1093/geronj/45.4.b113. [DOI] [PubMed] [Google Scholar]
  27. Giustina A., Veldhuis J. D. Pathophysiology of the neuroregulation of growth hormone secretion in experimental animals and the human. Endocr Rev. 1998 Dec;19(6):717–797. doi: 10.1210/edrv.19.6.0353. [DOI] [PubMed] [Google Scholar]
  28. Gould J., Aramburo C., Capdevielle M., Scanes C. G. Angiogenic activity of anterior pituitary tissue and growth hormone on the chick embryo chorio-allantoic membrane: a novel action of GH. Life Sci. 1995;56(8):587–594. doi: 10.1016/0024-3205(94)00491-a. [DOI] [PubMed] [Google Scholar]
  29. Grant M. B., Mames R. N., Fitzgerald C., Ellis E. A., Caballero S., Chegini N., Guy J. Insulin-like growth factor I as an angiogenic agent. In vivo and in vitro studies. Ann N Y Acad Sci. 1993 Aug 27;692:230–242. doi: 10.1111/j.1749-6632.1993.tb26221.x. [DOI] [PubMed] [Google Scholar]
  30. Guttentag R. E., Madden D. J. Adult age differences in the attentional capacity demands of letter matching. Exp Aging Res. 1987 Spring-Summer;13(1-2):93–99. doi: 10.1080/03610738708259307. [DOI] [PubMed] [Google Scholar]
  31. Hasenöhrl R. U., Söderstróm S., Mohammed A. H., Ebendal T., Huston J. P. Reciprocal changes in expression of mRNA for nerve growth factor and its receptors TrkA and LNGFR in brain of aged rats in relation to maze learning deficits. Exp Brain Res. 1997 Apr;114(2):205–213. doi: 10.1007/pl00005629. [DOI] [PubMed] [Google Scholar]
  32. Hepler J. E., Lund P. K. Molecular biology of the insulin-like growth factors. Relevance to nervous system function. Mol Neurobiol. 1990 Spring-Summer;4(1-2):93–127. doi: 10.1007/BF02935586. [DOI] [PubMed] [Google Scholar]
  33. Hultsch D. F., Hertzog C., Dixon R. A. Ability correlates of memory performance in adulthood and aging. Psychol Aging. 1990 Sep;5(3):356–368. doi: 10.1037//0882-7974.5.3.356. [DOI] [PubMed] [Google Scholar]
  34. Hynes M. A., Van Wyk J. J., Brooks P. J., D'Ercole A. J., Jansen M., Lund P. K. Growth hormone dependence of somatomedin-C/insulin-like growth factor-I and insulin-like growth factor-II messenger ribonucleic acids. Mol Endocrinol. 1987 Mar;1(3):233–242. doi: 10.1210/mend-1-3-233. [DOI] [PubMed] [Google Scholar]
  35. Kaleko M., Rutter W. J., Miller A. D. Overexpression of the human insulinlike growth factor I receptor promotes ligand-dependent neoplastic transformation. Mol Cell Biol. 1990 Feb;10(2):464–473. doi: 10.1128/mcb.10.2.464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Kalu D. N., Orhii P. B., Chen C., Lee D. Y., Hubbard G. B., Lee S., Olatunji-Bello Y. Aged-rodent models of long-term growth hormone therapy: lack of deleterious effect on longevity. J Gerontol A Biol Sci Med Sci. 1998 Nov;53(6):B452–B463. doi: 10.1093/gerona/53a.6.b452. [DOI] [PubMed] [Google Scholar]
  37. Khansari D. N., Gustad T. Effects of long-term, low-dose growth hormone therapy on immune function and life expectancy of mice. Mech Ageing Dev. 1991 Jan;57(1):87–100. doi: 10.1016/0047-6374(91)90026-v. [DOI] [PubMed] [Google Scholar]
  38. Laron Z., Aran O., Nofar E., Beit-Halachmi N., Pertzelan A., Galatzer A. Psychosocial aspects of young adult growth hormone deficient patients previously treated with human growth hormone--a preliminary report. Acta Paediatr Scand Suppl. 1986;325:80–82. doi: 10.1111/j.1651-2227.1986.tb10370.x. [DOI] [PubMed] [Google Scholar]
  39. Lee A. V., Darbre P., King R. J. Processing of insulin-like growth factor-II (IGF-II) by human breast cancer cells. Mol Cell Endocrinol. 1994 Mar;99(2):211–220. doi: 10.1016/0303-7207(94)90010-8. [DOI] [PubMed] [Google Scholar]
  40. Light L. L. Memory and aging: four hypotheses in search of data. Annu Rev Psychol. 1991;42:333–376. doi: 10.1146/annurev.ps.42.020191.002001. [DOI] [PubMed] [Google Scholar]
  41. Lynch C. D., Cooney P. T., Bennett S. A., Thornton P. L., Khan A. S., Ingram R. L., Sonntag W. E. Effects of moderate caloric restriction on cortical microvascular density and local cerebral blood flow in aged rats. Neurobiol Aging. 1999 Mar-Apr;20(2):191–200. doi: 10.1016/s0197-4580(99)00032-9. [DOI] [PubMed] [Google Scholar]
  42. Lärkfors L., Ebendal T., Whittemore S. R., Persson H., Hoffer B., Olson L. Decreased level of nerve growth factor (NGF) and its messenger RNA in the aged rat brain. Brain Res. 1987 Dec;427(1):55–60. doi: 10.1016/0169-328x(87)90044-1. [DOI] [PubMed] [Google Scholar]
  43. López-Fernández J., Sánchez-Franco F., Velasco B., Tolón R. M., Pazos F., Cacicedo L. Growth hormone induces somatostatin and insulin-like growth factor I gene expression in the cerebral hemispheres of aging rats. Endocrinology. 1996 Oct;137(10):4384–4391. doi: 10.1210/endo.137.10.8828499. [DOI] [PubMed] [Google Scholar]
  44. Markowska A. L., Koliatsos V. E., Breckler S. J., Price D. L., Olton D. S. Human nerve growth factor improves spatial memory in aged but not in young rats. J Neurosci. 1994 Aug;14(8):4815–4824. doi: 10.1523/JNEUROSCI.14-08-04815.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Markowska A. L., Mooney M., Sonntag W. E. Insulin-like growth factor-1 ameliorates age-related behavioral deficits. Neuroscience. 1998 Dec;87(3):559–569. doi: 10.1016/s0306-4522(98)00143-2. [DOI] [PubMed] [Google Scholar]
  46. McCubrey J. A., Steelman L. S., Mayo M. W., Algate P. A., Dellow R. A., Kaleko M. Growth-promoting effects of insulin-like growth factor-1 (IGF-1) on hematopoietic cells: overexpression of introduced IGF-1 receptor abrogates interleukin-3 dependency of murine factor-dependent cells by a ligand-dependent mechanism. Blood. 1991 Aug 15;78(4):921–929. [PubMed] [Google Scholar]
  47. McDonald J. W., Johnston M. V. Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res Brain Res Rev. 1990 Jan-Apr;15(1):41–70. doi: 10.1016/0165-0173(90)90011-c. [DOI] [PubMed] [Google Scholar]
  48. Michaelis E. K. Molecular biology of glutamate receptors in the central nervous system and their role in excitotoxicity, oxidative stress and aging. Prog Neurobiol. 1998 Mar;54(4):369–415. doi: 10.1016/s0301-0082(97)00055-5. [DOI] [PubMed] [Google Scholar]
  49. Moss M. B., Rosene D. L., Peters A. Effects of aging on visual recognition memory in the rhesus monkey. Neurobiol Aging. 1988 Sep-Dec;9(5-6):495–502. doi: 10.1016/s0197-4580(88)80103-9. [DOI] [PubMed] [Google Scholar]
  50. Nakao-Hayashi J., Ito H., Kanayasu T., Morita I., Murota S. Stimulatory effects of insulin and insulin-like growth factor I on migration and tube formation by vascular endothelial cells. Atherosclerosis. 1992 Feb;92(2-3):141–149. doi: 10.1016/0021-9150(92)90273-j. [DOI] [PubMed] [Google Scholar]
  51. Niblock M. M., Brunso-Bechtold J. K., Lynch C. D., Ingram R. L., McShane T., Sonntag W. E. Distribution and levels of insulin-like growth factor I mRNA across the life span in the Brown Norway x Fischer 344 rat brain. Brain Res. 1998 Aug 31;804(1):79–86. doi: 10.1016/s0006-8993(98)00645-3. [DOI] [PubMed] [Google Scholar]
  52. Nicosia R. F., Nicosia S. V., Smith M. Vascular endothelial growth factor, platelet-derived growth factor, and insulin-like growth factor-1 promote rat aortic angiogenesis in vitro. Am J Pathol. 1994 Nov;145(5):1023–1029. [PMC free article] [PubMed] [Google Scholar]
  53. Peterson C., Cotman C. W. Strain-dependent decrease in glutamate binding to the N-methyl-D-aspartic acid receptor during aging. Neurosci Lett. 1989 Oct 9;104(3):309–313. doi: 10.1016/0304-3940(89)90594-6. [DOI] [PubMed] [Google Scholar]
  54. Petralia R. S., Wang Y. X., Wenthold R. J. The NMDA receptor subunits NR2A and NR2B show histological and ultrastructural localization patterns similar to those of NR1. J Neurosci. 1994 Oct;14(10):6102–6120. doi: 10.1523/JNEUROSCI.14-10-06102.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Peyrat J. P., Bonneterre J. Type 1 IGF receptor in human breast diseases. Breast Cancer Res Treat. 1992;22(1):59–67. doi: 10.1007/BF01833334. [DOI] [PubMed] [Google Scholar]
  56. Pietrzkowski Z., Wernicke D., Porcu P., Jameson B. A., Baserga R. Inhibition of cellular proliferation by peptide analogues of insulin-like growth factor 1. Cancer Res. 1992 Dec 1;52(23):6447–6451. [PubMed] [Google Scholar]
  57. Rapp P. R., Amaral D. G. Evidence for task-dependent memory dysfunction in the aged monkey. J Neurosci. 1989 Oct;9(10):3568–3576. doi: 10.1523/JNEUROSCI.09-10-03568.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Reinhardt R. R., Bondy C. A. Insulin-like growth factors cross the blood-brain barrier. Endocrinology. 1994 Nov;135(5):1753–1761. doi: 10.1210/endo.135.5.7525251. [DOI] [PubMed] [Google Scholar]
  59. Renganathan M., Sonntag W. E., Delbono O. L-type Ca2+ channel-insulin-like growth factor-1 receptor signaling impairment in aging rat skeletal muscle. Biochem Biophys Res Commun. 1997 Jun 27;235(3):784–789. doi: 10.1006/bbrc.1997.6881. [DOI] [PubMed] [Google Scholar]
  60. Rudman D., Feller A. G., Nagraj H. S., Gergans G. A., Lalitha P. Y., Goldberg A. F., Schlenker R. A., Cohn L., Rudman I. W., Mattson D. E. Effects of human growth hormone in men over 60 years old. N Engl J Med. 1990 Jul 5;323(1):1–6. doi: 10.1056/NEJM199007053230101. [DOI] [PubMed] [Google Scholar]
  61. Russell W. E., Van Wyk J. J., Pledger W. J. Inhibition of the mitogenic effects of plasma by a monoclonal antibody to somatomedin C. Proc Natl Acad Sci U S A. 1984 Apr;81(8):2389–2392. doi: 10.1073/pnas.81.8.2389. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Sartorio A., Molinari E., Riva G., Conti A., Morabito F., Faglia G. Growth hormone treatment in adults with childhood onset growth hormone deficiency: effects on psychological capabilities. Horm Res. 1995;44(1):6–11. doi: 10.1159/000184582. [DOI] [PubMed] [Google Scholar]
  63. Sato Y., Okamura K., Morimoto A., Hamanaka R., Hamaguchi K., Shimada T., Ono M., Kohno K., Sakata T., Kuwano M. Indispensable role of tissue-type plasminogen activator in growth factor-dependent tube formation of human microvascular endothelial cells in vitro. Exp Cell Res. 1993 Feb;204(2):223–229. doi: 10.1006/excr.1993.1028. [DOI] [PubMed] [Google Scholar]
  64. Sonntag W. E., Boyd R. L., Booze R. M. Somatostatin gene expression in hypothalamus and cortex of aging male rats. Neurobiol Aging. 1990 Jul-Aug;11(4):409–416. doi: 10.1016/0197-4580(90)90007-m. [DOI] [PubMed] [Google Scholar]
  65. Sonntag W. E., Hylka V. W., Meites J. Growth hormone restores protein synthesis in skeletal muscle of old male rats. J Gerontol. 1985 Nov;40(6):689–694. doi: 10.1093/geronj/40.6.689. [DOI] [PubMed] [Google Scholar]
  66. Sonntag W. E., Lynch C. D., Bennett S. A., Khan A. S., Thornton P. L., Cooney P. T., Ingram R. L., McShane T., Brunso-Bechtold J. K. Alterations in insulin-like growth factor-1 gene and protein expression and type 1 insulin-like growth factor receptors in the brains of ageing rats. Neuroscience. 1999 Jan;88(1):269–279. doi: 10.1016/s0306-4522(98)00192-4. [DOI] [PubMed] [Google Scholar]
  67. Sonntag W. E., Lynch C. D., Cefalu W. T., Ingram R. L., Bennett S. A., Thornton P. L., Khan A. S. Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals. J Gerontol A Biol Sci Med Sci. 1999 Dec;54(12):B521–B538. doi: 10.1093/gerona/54.12.b521. [DOI] [PubMed] [Google Scholar]
  68. Sonntag W. E., Lynch C. D., Cooney P. T., Hutchins P. M. Decreases in cerebral microvasculature with age are associated with the decline in growth hormone and insulin-like growth factor 1. Endocrinology. 1997 Aug;138(8):3515–3520. doi: 10.1210/endo.138.8.5330. [DOI] [PubMed] [Google Scholar]
  69. Steger R. W., Bartke A., Cecim M. Premature ageing in transgenic mice expressing different growth hormone genes. J Reprod Fertil Suppl. 1993;46:61–75. [PubMed] [Google Scholar]
  70. Thornton P. L., Ingram R. L., Sonntag W. E. Chronic [D-Ala2]-growth hormone-releasing hormone administration attenuates age-related deficits in spatial memory. J Gerontol A Biol Sci Med Sci. 2000 Feb;55(2):B106–B112. doi: 10.1093/gerona/55.2.b106. [DOI] [PubMed] [Google Scholar]
  71. Torrisi R., Pensa F., Orengo M. A., Catsafados E., Ponzani P., Boccardo F., Costa A., Decensi A. The synthetic retinoid fenretinide lowers plasma insulin-like growth factor I levels in breast cancer patients. Cancer Res. 1993 Oct 15;53(20):4769–4771. [PubMed] [Google Scholar]
  72. Wang Y. Z., Wong Y. C. Sex hormone-induced prostatic carcinogenesis in the noble rat: the role of insulin-like growth factor-I (IGF-I) and vascular endothelial growth factor (VEGF) in the development of prostate cancer. Prostate. 1998 May 15;35(3):165–177. doi: 10.1002/(sici)1097-0045(19980515)35:3<165::aid-pros2>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
  73. Weindruch R. The retardation of aging by caloric restriction: studies in rodents and primates. Toxicol Pathol. 1996 Nov-Dec;24(6):742–745. doi: 10.1177/019262339602400618. [DOI] [PubMed] [Google Scholar]
  74. Werner H., LeRoith D. The role of the insulin-like growth factor system in human cancer. Adv Cancer Res. 1996;68:183–223. doi: 10.1016/s0065-230x(08)60354-1. [DOI] [PubMed] [Google Scholar]
  75. West R. L., Crook T. H., Barron K. L. Everyday memory performance across the life span: effects of age and noncognitive individual differences. Psychol Aging. 1992 Mar;7(1):72–82. doi: 10.1037//0882-7974.7.1.72. [DOI] [PubMed] [Google Scholar]
  76. Zornetzer S. F., Thompson R., Rogers J. Rapid forgetting in aged rats. Behav Neural Biol. 1982 Sep;36(1):49–60. doi: 10.1016/s0163-1047(82)90234-5. [DOI] [PubMed] [Google Scholar]

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