Advertisement

Glucocorticoids and Dehydroepiandrosterone: A Role in Immunosenescence?

  • Moisés E. Bauer
Living reference work entry

Abstract

This chapter summarizes current evidence suggesting that immunosenescence may be influenced by both psychological stress and stress hormones. The age-related immunological changes are also similarly found during chronic stress, bipolar disease, or chronic glucocorticoid exposure. It follows that endogenous glucocorticoids (cortisol) could be associated to immunosenescence. Previous studies have shown that healthy older adults are emotionally distressed in parallel to increased cortisol/dehydroepiandrosterone (DHEA) ratio. Furthermore, chronic stressed older adults may be particularly at risk of stress-related pathology because of further alterations in glucocorticoid-immune signaling. Although DHEA and its metabolites have been described with immune-enhancing properties, their potential use as hormonal boosters of immunity should be interpreted with caution. The psychoneuroendocrine hypothesis of immunosenescence is presented in which the age-related increase in the cortisol/DHEA ratio is the major determinant of immunological changes observed during aging. Finally, preliminary evidence indicated that stress-management interventions in older adults are capable of attenuating some important features of immunosenescence.

Keywords

Aging Immunosenescence Glucocorticoids Lymphocytes 

Notes

Acknowledgments

This study was supported by grants from CNPq and FAPERGS.

References

  1. Adcock IM, Lane SJ, Brown CR, Lee TH, Barnes PJ (1995) Abnormal glucocorticoid receptor-activator protein 1 interaction in steroid-resistant asthma. J Exp Med 182:1951–1958PubMedCrossRefGoogle Scholar
  2. Araneo B, Woods M, Daynes R (1993) Reversal of the immunosenescent phenotype by dehydroepiandrosterone: hormone treatment provides an adjuvant effect on the immunization of aged mice with recombinant hepatitis B surface antigen. J Infect Dis 167:830–840PubMedCrossRefGoogle Scholar
  3. Arnetz BB, Theorell T, Levi L, Kallner A, Eneroth P (1983) An experimental study of social isolation of elderly people: psychoendocrine and metabolic effects. Psychosom Med 45:395–406PubMedCrossRefGoogle Scholar
  4. Aspinall R, Del Giudice G, Effros RB, Grubeck-Loebenstein B, Sambhara S (2007) Challenges for vaccination in the elderly. Immun Ageing 4:9PubMedPubMedCentralCrossRefGoogle Scholar
  5. Auci D, Kaler L, Subramanian S, Huang Y, Frincke J, Reading C, Offner H (2007) A new orally bioavailable synthetic androstene inhibits collagen-induced arthritis in the mouse: androstene hormones as regulators of regulatory T cells. Ann N Y Acad Sci 1110:630–640PubMedCrossRefGoogle Scholar
  6. Bauer ME (2005) Stress, glucocorticoids and ageing of the immune system. Stress 8:69–83PubMedCrossRefGoogle Scholar
  7. Bauer ME (2008) Chronic stress and immunosenescence: a review. Neuroimmunomodulation 15:241–250PubMedCrossRefGoogle Scholar
  8. Bauer ME, Vedhara K, Perks P, Wilcock G, Lightman S, Shanks N (2000) Chronic stress in caregivers of dementia patients is associated with reduced lymphocyte sensitivity to glucocorticoids. J Neuroimmunol 103:84–92PubMedCrossRefGoogle Scholar
  9. Bauer ME, Papadopoulos A, Poon L, Perks P, Lightman S, Checkley S, Shanks N (2002) Dexamethasone-induced effects on lymphocyte distribution and expression of adhesion molecules in treatment resistant major depression. Psychiatry Res 113:1–15PubMedCrossRefGoogle Scholar
  10. Bauer ME, Papadopoulos A, Poon L, Perks P, Lightman S, Checkley S, Shanks N (2003) Altered glucocorticoid immunoregulation in treatment resistant depression. Psychoneuroendocrinology 28:49–65PubMedCrossRefGoogle Scholar
  11. Bauer ME, Jeckel CM, Luz C (2009) The role of stress factors during aging of the immune system. Ann N Y Acad Sci 1153:139–152PubMedCrossRefGoogle Scholar
  12. Ben-Yehuda A, Danenberg H, Zakay-Rones Z, Gross D, Friedman G (1998) The influence of sequential annual vaccination and DHEA administration on the efficacy of the immune response to influenza vaccine in the elderly. Mech Ageing Dev 102:299–306PubMedCrossRefGoogle Scholar
  13. Besedovsky H, Sorkin E, Felix D, Haas H (1977) Hypothalamic changes during the immune response. Eur J Immunol 7:323–325PubMedCrossRefGoogle Scholar
  14. Besedovsky L, Linz B, Dimitrov S, Groch S, Born J, Lange T (2014) Cortisol increases CXCR4 expression but does not affect CD62L and CCR7 levels on specific T cell subsets in humans. Am J Physiol Endocrinol Metab 306:E1322–E1329PubMedCrossRefGoogle Scholar
  15. Bosch JA, Fischer JE, Fischer JC (2009) Psychologically adverse work conditions are associated with CD8+ T cell differentiation indicative of immunesenescence. Brain Behav Immun 23:527–534PubMedCrossRefGoogle Scholar
  16. Bronnegard M, Stierna P, Marcus C (1996) Glucocorticoid resistant syndromes – molecular basis and clinical presentations. J Neuroendocrinol 8:405–415PubMedCrossRefGoogle Scholar
  17. Butcher SK, Lord JM (2004) Stress responses and innate immunity: aging as a contributory factor. Aging Cell 3:151–160PubMedCrossRefGoogle Scholar
  18. Buvat J (2003) Androgen therapy with dehydroepiandrosterone. World J Urol 21:346–355PubMedCrossRefGoogle Scholar
  19. Calabrese EJ (2008) Hormesis and medicine. Br J Clin Pharmacol 66:594–617PubMedPubMedCentralGoogle Scholar
  20. Calabrese EJ, Iavicoli I, Calabrese V (2012) Hormesis: why it is important to biogerontologists. Biogerontology 13:215–235PubMedCrossRefGoogle Scholar
  21. Canning MO, Grotenhuis K, De Wit HJ, Drexhage HA (2000) Opposing effects of dehydroepiandrosterone and dexamethasone on the generation of monocyte-derived dendritic cells. Eur J Endocrinol 143:687–695PubMedCrossRefGoogle Scholar
  22. Carvalho LA, Bergink V, Sumaski L, Wijkhuijs J, Hoogendijk WJ, Birkenhager TK, Drexhage HA (2014) Inflammatory activation is associated with a reduced glucocorticoid receptor alpha/beta expression ratio in monocytes of inpatients with melancholic major depressive disorder. Transl Psychiatry 4:e344PubMedPubMedCentralCrossRefGoogle Scholar
  23. Casson PR, Andersen RN, Herrod HG, Stentz FB, Straughn AB, Abraham GE, Buster JE (1993) Oral dehydroepiandrosterone in physiologic doses modulates immune function in postmenopausal women. Am J Obstet Gynecol 169:1536–1539PubMedCrossRefGoogle Scholar
  24. Castro M, Elliot S, Kino T, Bamberger C, Karl M, Webster E, Chrousos G (1996) The non-ligand binding beta-isoform of the human glucocorticoid receptor (hGC-beta): tissue levels, mechanism of action, and potential physiologic role. Mol Med 2:597–607PubMedPubMedCentralCrossRefGoogle Scholar
  25. Chen X, Murakami T, Oppenheim JJ, Howard OM (2004) Differential response of murine CD4+CD25+ and CD4+CD25- T cells to dexamethasone-induced cell death. Eur J Immunol 34:859–869PubMedCrossRefGoogle Scholar
  26. Collaziol D, Luz C, Dornelles F, Cruz I, Bauer ME (2004) Psychoneuroendocrine correlates of lymphocyte subsets during healthy ageing. Mech Ageing Dev 125:219–227PubMedCrossRefGoogle Scholar
  27. Danenberg H, Ben-Yehuda A, Zakay-Rones Z, Friedman G (1995) Dehydroepiandrosterone (DHEA) treatment reverses the impaired immune response of old mice to influenza vaccination and protects from influenza infection. Vaccine 13:1445–1448PubMedCrossRefGoogle Scholar
  28. Danenberg HD, Ben-Yehuda A, Zakay-Rones Z, Gross DJ, Friedman G (1997) Dehydroepiandrosterone treatment is not beneficial to the immune response to influenza in elderly subjects. J Clin Endocrinol Metab 82:2911–2914PubMedGoogle Scholar
  29. Daynes R, Dudley D, Araneo B (1990) Regulation of murine lymphokine production in vivo. II. Dehydroepiandrosterone is a natural enhancer of interleukin-2 synthesis by helper T cells. Eur J Immunol 20:793–802PubMedCrossRefGoogle Scholar
  30. Daynes R, Araneo B, Ershler W, Maloney C, Li G-Z, Ryu S-Y (1993) Altered regulation of IL-6 production with normal aging – possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. J Immunol 150:5219–5230PubMedGoogle Scholar
  31. De Kloet ER, Vreugdenhil E, Oitzl MS, Joels M (1998) Brain corticosteroid receptor balance in health and disease. Endocr Rev 19:269–301PubMedGoogle Scholar
  32. Degelau J, Guay D, Hallgren H (1997) The effect of DHEAS on influenza vaccination in aging adults. J Am Geriatr Soc 45:747–751PubMedCrossRefGoogle Scholar
  33. Deuschle M, Gotthardt U, Schweiger U, Weber B, Korner A, Schmider J, Standhardt H, Lammers C, Heuser I (1997) With aging in humans the activity of the hypothalamus-pituitary-adrenal system increases and its amplitude flattens. Life Sci 61:2239–2246PubMedCrossRefGoogle Scholar
  34. Dew MA, Reynolds CF, Frank E, Begley AE, Miller MD, Cornes C, Mazumdar S, Perel JM, Kupfer DJ (1998) Effects of age at onset of first lifetime episode of recurrent major depression on treatment response and illness course in elderly patients. Am J Psychiatry 155:759–799Google Scholar
  35. Dhabhar FS (2009) Enhancing versus suppressive effects of stress on immune function: implications for immunoprotection and immunopathology. Neuroimmunomodulation 16:300–317PubMedPubMedCentralCrossRefGoogle Scholar
  36. Dhabhar FS (2014) Effects of stress on immune function: the good, the bad, and the beautiful. Immunol Res 58:193–210PubMedCrossRefGoogle Scholar
  37. Di Santo E, Sironi M, Mennini T (1996) A glucocorticoid receptor independent mechanism for neurosteroid inhibition of tumor necrosis factor production. Eur J Pharmacol 299:179–186PubMedCrossRefGoogle Scholar
  38. Dimitrov S, Benedict C, Heutling D, Westermann J, Born J, Lange T (2009) Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood 113:5134–5143PubMedPubMedCentralCrossRefGoogle Scholar
  39. Dowlati Y, Herrmann N, Swardfager W, Liu H, Sham L, Reim EK, Lanctot KL (2010) A meta-analysis of cytokines in major depression. Biol Psychiatry 67:446–457PubMedCrossRefGoogle Scholar
  40. Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM (2004) Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A 101:17312–17315PubMedPubMedCentralCrossRefGoogle Scholar
  41. Evans TG, Judd ME, Dowell T, Poe S, Daynes RA, Araneo BA (1996) The use of oral dehydroepiandrosterone sulfate as an adjuvant in tetanus and influenza vaccination of the elderly. Vaccine 14:1531–1537PubMedCrossRefGoogle Scholar
  42. Faria AM, De Moraes SM, De Freitas LH, Speziali E, Soares TF, Figueiredo-Neves SP, Vitelli-Avelar DM, Martins MA, Barbosa KV, Soares EB, Sathler-Avelar R, Peruhype-Magalhaes V, Cardoso GM, Comin F, Teixeira R, Eloi-Santos SM, Queiroz DM, Correa-Oliveira R, Bauer ME, Teixeira-Carvalho A, Martins-Filho OA (2008) Variation rhythms of lymphocyte subsets during healthy aging. Neuroimmunomodulation 15:365–379PubMedCrossRefGoogle Scholar
  43. Fauci A (1975) Mechanisms of corticosteroid action on lymphocyte subpopulations. Immunology 28:669–679PubMedPubMedCentralGoogle Scholar
  44. Ferrari E, Arcaini A, Gornati R, Pelanconi L, Cravello L, Fioravanti M, Solerte SB, Magri F (2000) Pineal and pituitary-adrenocortical function in physiological aging and in senile dementia. Exp Gerontol 35:1239–1250PubMedCrossRefGoogle Scholar
  45. Ferrari E, Cravello L, Muzzoni B, Casaritti D, Paltro M, Sorlete SB, Fioravanti M, Cuzzoni G, Pontiggia B, Magri F (2001) Age-related changes of the hypothalamic-pituitary-adrenal axis: pathophysiological correlates. Eur J Endocrinol 144:319–329PubMedCrossRefGoogle Scholar
  46. Ferrari E, Mirani M, Barili L, Falvo F, Solerte SB, Cravello L, Pini L, Magri F (2004) Cognitive and affective disorders in the elderly: a neuroendocrine study. Arch Gerontol Geriatr 9(Suppl):171–182CrossRefGoogle Scholar
  47. 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–S9PubMedCrossRefGoogle Scholar
  48. Fulop T, Larbi A, Pawelec G (2013) Human T cell aging and the impact of persistent viral infections. Front Immunol 4:271PubMedPubMedCentralCrossRefGoogle Scholar
  49. Gabriel H, Schmitt B, Kindermann W (1993) Age-related increase of CD45RO+ lymphocytes in physically active adults. Eur J Immunol 23:2704–2706PubMedCrossRefGoogle Scholar
  50. Galon J, Franchimont D, Hiroi N, Frey G, Boetner A, Ehrart-Bornstein M, O’Shea J, Chrousos GP, Bornstein S (2002) Gene profiling reveals unknown enhancing and suppressive actions of glucocorticoids on immune cells. FASEB J 16:61–71PubMedCrossRefGoogle Scholar
  51. Glaser R, Kiecolt-Glaser JK (2005) Stress-induced immune dysfunction: implications for health. Nat Rev Immunol 5:243–251PubMedCrossRefGoogle Scholar
  52. Glaser R, Sheridan J, Malarkey WB, Maccallum RC, Kiecolt-Glaser JK (2000) Chronic stress modulates the immune response to a pneumococcal pneumonia vaccine. Psychosom Med 62:804–807PubMedCrossRefGoogle Scholar
  53. Gold R, Buttgereit F, Toyka KV (2001) Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders. J Neuroimmunol 117:1–8PubMedCrossRefGoogle Scholar
  54. Goronzy JJ, Shao L, Weyand CM (2010) Immune aging and rheumatoid arthritis. Rheum Dis Clin N Am 36:297–310CrossRefGoogle Scholar
  55. Gouin JP, Hantsoo L, Kiecolt-Glaser JK (2008) Immune dysregulation and chronic stress among older adults: a review. Neuroimmunomodulation 15:251–259PubMedPubMedCentralCrossRefGoogle Scholar
  56. Grasso G, Lodi L, Lupo C, Muscettola M (1997) Glucocorticoid receptors in human peripheral blood mononuclear cells in relation to age and to sport activity. Life Sci 61:301–308PubMedCrossRefGoogle Scholar
  57. Halbreich U, Asnis G, Zumoff B, Nathan R, Shindledecker R (1984) Effect of age and sex on cortisol secretion in depressives and normals. Psychiatry Res 13:221–229PubMedCrossRefGoogle Scholar
  58. Hannet I, Erkeller-Yuksel F, Lydyard P, Deneys V, Debruyere M (1992) Developmental and maturational changes in human blood lymphocyte subpopulations. Immunol Today 13:215, 218PubMedCrossRefGoogle Scholar
  59. Hazeldine J, Arlt W, Lord JM (2010) Dehydroepiandrosterone as a regulator of immune cell function. J Steroid Biochem Mol Biol 120:127–136PubMedCrossRefGoogle Scholar
  60. Hearing SD, Norman M, Smyth C, Foy C, Dayan CM (1999) Wide variation in lymphocyte steroid sensitivity among healthy human volunteers. J Clin Endocrinol Metab 84:4149–4154PubMedGoogle Scholar
  61. Heuser I, Deuschle M, Luppa P, Schweiger U, Standhadt H, Weber B (1998) Increased diurnal plasma concentrations of dehydroepiandrosterone in depressed patients. J Clin Endocrinol Metab 83:3130–3133PubMedCrossRefGoogle Scholar
  62. Hirokawa K, Makinodan T (1975) Thymic involution: effect on T cell differentiation. J Immunol 114:1659–1664PubMedGoogle Scholar
  63. Hoglund CO, Axen J, Kemi C, Jernelov S, Grunewald J, Muller-Suur C, Smith Y, Gronneberg R, Eklund A, Stierna P, Lekander M (2006) Changes in immune regulation in response to examination stress in atopic and healthy individuals. Clin Exp Allergy 36:982–992PubMedCrossRefGoogle Scholar
  64. Horvath S (2013) DNA methylation age of human tissues and cell types. Genome Biol 14:R115PubMedPubMedCentralCrossRefGoogle Scholar
  65. Howieson DB, Camicioli R, Quinn J, Silbert LC, Care B, Moore MM, Dame A, Sexton G, Kaye JA (2003) Natural history of cognitive decline in the old old. Neurology 60:1489–1494PubMedCrossRefGoogle Scholar
  66. Jagger A, Shimojima Y, Goronzy JJ, Weyand CM (2014) Regulatory T cells and the immune aging process: a mini-review. Gerontology 60:130–137PubMedCrossRefGoogle Scholar
  67. Kam J, Szefler S, Surs W, Sher E, Leung D (1993) Combination of IL-2 and IL-4 reduces glucocorticoid receptor- binding affinity and T cell response to glucocorticoids. J Immunol 151:3460–3466PubMedGoogle Scholar
  68. Kavelaars A, Cats B, Visser G, Zegers B, Bakker J, Van Rees E, Heijnen C (1996) Ontogeny of the response of human peripheral blood T cells to glucocorticoids. Brain Behav Immun 10:288–297PubMedCrossRefGoogle Scholar
  69. Kiecolt-Glaser J, Dura J, Speicher C, Trask J, Glaser R (1991) Spousal caregivers of dementia victims: longitudinal changes in immunity and health. Psychosom Med 53:345–362PubMedCrossRefGoogle Scholar
  70. Kiecolt-Glaser J, Marucha P, Malarkey W, Mercado A, Glaser R (1995) Slowing of wound healing by psychological stress. Lancet 346:1194–1196PubMedCrossRefGoogle Scholar
  71. Kiecolt-Glaser J, Glaser R, Gravenstein S, Malarkey W, Sheridan J (1996) Chronic stress alters the immune response to influenza virus vaccine in older adults. Proc Natl Acad Sci U S A 93:3043–3047PubMedPubMedCentralCrossRefGoogle Scholar
  72. Kiecolt-Glaser JK, Preacher KJ, Maccallum RC, Atkinson C, Malarkey WB, Glaser R (2003) Chronic stress and age-related increases in the proinflammatory cytokine IL-6. Proc Natl Acad Sci U S A 100:9090–9095PubMedPubMedCentralCrossRefGoogle Scholar
  73. Kleyer A, Schett G (2014) Arthritis and bone loss: a hen and egg story. Curr Opin Rheumatol 26:80–84PubMedCrossRefGoogle Scholar
  74. Lee AL, Ogle WO, Sapolsky RM (2002) Stress and depression: possible links to neuron death in the hippocampus. Bipolar Disord 4:117–128PubMedCrossRefGoogle Scholar
  75. Licastro F, Candore G, Lio D, Porcellini E, Colonna-Romano G, Franceschi C, Caruso C (2005) Innate immunity and inflammation in ageing: a key for understanding age-related diseases. Immun Ageing 2:8PubMedPubMedCentralCrossRefGoogle Scholar
  76. Ligthart G, Corberand J, Fournier C, Galanaud P, Humans W, Kennes B, Möller-Hermelink H, Steinmann G (1984) Admission criteria for immunogerontological studies in man: the SENIEUR protocol. Mech Ageing Dev 28:47–55PubMedCrossRefGoogle Scholar
  77. Lupien S, Lecours A, Lussier I, Schwartz G, Nair N, Meaney M (1994) Basal cortisol levels and cognitive deficits in human aging. J Neurosci 14:2893–2903PubMedCrossRefGoogle Scholar
  78. Luz C, Dornelles F, Scapini E, Collaziol D, Preissler T, Cruz I, Bauer ME (2002) Psychological and nutritional correlates of T-cell function in the healthy elderly. Stress 5:80–80Google Scholar
  79. Luz C, Dornelles F, Preissler T, Collaziol D, Cruz I, Bauer ME (2003) Impact of psychological and endocrine factors on cytokine production of healthy elderly people. Mech Ageing Dev 124:887–895PubMedCrossRefGoogle Scholar
  80. Luz C, Collaziol D, Preissler T, Da Cruz IM, Glock L, Bauer ME (2006) Healthy aging is associated with unaltered production of immunoreactive growth hormone but impaired neuroimmunomodulation. Neuroimmunomodulation 13:160–169PubMedCrossRefGoogle Scholar
  81. Maes M, Scharp S, Meltzer H, Bosmans E, Suy E, Calabrese J, Cosyns P (1993) Relationships between interleukin-6 activity, acute phase proteins, and function of the hypothalamic-pituitary-adrenal axis in severe depression. Psychiatry Res 49:11–27PubMedCrossRefGoogle Scholar
  82. Martinez-Taboada V, Bartolome MJ, Amado JA, Blanco R, Garcia-Unzueta MT, Rodriguez-Valverde V, Lopez-Hoyos M (2002) Changes in peripheral blood lymphocyte subsets in elderly subjects are associated with an impaired function of the hypothalamic-pituitary- adrenal axis. Mech Ageing Dev 123:1477–1486PubMedCrossRefGoogle Scholar
  83. Mastorakos G, Chrousos GP, Weber J (1993) Recombinant IL-6 activates the hypothalamic-pituitary-adrenal axis in humans. J Clin Endocrinol Metab 77:1690–1694PubMedGoogle Scholar
  84. Matthews JG, Ito K, Barnes PJ, Adcock IM (2004) Defective glucocorticoid receptor nuclear translocation and altered histone acetylation patterns in glucocorticoid-resistant patients. J Allergy Clin Immunol 113:1100–1108PubMedCrossRefGoogle Scholar
  85. Mcewen B (1998) Protective and damaging effects of stress mediators. N Engl J Med 338:171–179PubMedCrossRefGoogle Scholar
  86. Mcewen BS (2003) Interacting mediators of allostasis and allostatic load: towards an understanding of resilience in aging. Metabolism 52:10–16PubMedCrossRefGoogle Scholar
  87. Mcewen B, Biron C, Brunson K, Bulloch K, Chambers W, Dhabhar F, Goldfarb R, Kitson R, Miller A, Spencer R, Weiss J (1997) The role of adrenocorticosteroids as modulators of immune function in health and disease: neural, endocrine and immune interactions. Brain Res Rev 23:79–133PubMedCrossRefGoogle Scholar
  88. Mclachlan JA, Serkin CD, Bakouche O (1996) Dehydroepiandrosterone modulation of lipopolysaccharide-stimulated monocyte cytotoxicity. J Immunol 156:328–335PubMedGoogle Scholar
  89. Migeon C, Keller A, Lawrence B, Shepard T (1957) Dehydroepiandrosterone and androsterone levels in human plasma: effects of age, sex, day to day diurnal variations. J Clin Endocrinol Metab 17:1051PubMedCrossRefGoogle Scholar
  90. Miller GE, Chen E, Sze J, Marin T, Arevalo JM, Doll R, Ma R, Cole SW (2008) A functional genomic fingerprint of chronic stress in humans: blunted glucocorticoid and increased NF-kappa B signaling. Biol Psychiatry 64:266–272PubMedPubMedCentralCrossRefGoogle Scholar
  91. Moreno-Villanueva M, Burkle A (2015) Molecular consequences of psychological stress in human aging. Exp Gerontol 68:39–42PubMedCrossRefGoogle Scholar
  92. Murasko D, Weiner P, Kaye D (1987) Decline in mitogen induced proliferation of lymphocytes with increasing age. Clin Exp Immunol 70:440–448PubMedPubMedCentralGoogle Scholar
  93. Nagata S, Golstein P (1995) The Fas death factor. Science 267:1449–1456PubMedCrossRefGoogle Scholar
  94. Navarro J, Aristimuno C, Sanchez-Ramon S, Vigil D, Martinez-Gines ML, Fernandez-Cruz E, De Andres C (2006) Circulating dendritic cells subsets and regulatory T-cells at multiple sclerosis relapse: differential short-term changes on corticosteroids therapy. J Neuroimmunol 176:153–161PubMedCrossRefGoogle Scholar
  95. Nijhuis EW, Hinloopen B, Van Lier RA, Nagelkerken L (1995) Differential sensitivity of human naive and memory CD4+ T cells for dexamethasone. Int Immunol 7:591–595PubMedCrossRefGoogle Scholar
  96. Nikolich-Zugich J (2014) Aging of the T cell compartment in mice and humans: from no naive expectations to foggy memories. J Immunol 193:2622–2629PubMedPubMedCentralCrossRefGoogle Scholar
  97. Nolen-Hoeksema S, Ahrens C (2002) Age differences and similarities in the correlates of depressive symptoms. Psychol Aging 17:116–124PubMedCrossRefGoogle Scholar
  98. Oka M, Hirazawa K, Yamamoto K, Iizuka N, Hazama S, Suzuki T, Kobayashi N (1996) Induction of Fas-mediated apoptosis on circulating lymphocytes by surgical stress. Ann Surg 223:434–440PubMedPubMedCentralCrossRefGoogle Scholar
  99. Ouchi N, Parker JL, Lugus JJ, Walsh K (2011) Adipokines in inflammation and metabolic disease. Nat Rev Immunol 11:85–97PubMedPubMedCentralCrossRefGoogle Scholar
  100. Padgett DA, Loria R (1994) In vitro potentiation of lymphocyte activation by dehydroepiandrosterone, androstenediol, and androstenetriol. J Immunol 153:1544–1552PubMedGoogle Scholar
  101. Pariante C, Pearce B, Pisell T, Sanshez C, Po C, Su C, Miller A (1999a) The proinflammatory cytokine, interleukin-1α, reduces glucocorticoid receptor translocation and function. Endocrinology 140:4359–4366PubMedCrossRefGoogle Scholar
  102. Pariante CM, Pearce BD, Pisell TL, Sanchez CI, Po C, Su C, Miller AH (1999b) The proinflammatory cytokine, interleukin-1alpha, reduces glucocorticoid receptor translocation and function. Endocrinology 140:4359–4366PubMedCrossRefGoogle Scholar
  103. Pavao TS, Vianna P, Pillat MM, Machado AB, Bauer ME (2010) Acupuncture is effective to attenuate stress and stimulate lymphocyte proliferation in the elderly. Neurosci Lett 484:47–50PubMedCrossRefGoogle Scholar
  104. Pera A, Campos C, Lopez N, Hassouneh F, Alonso C, Tarazona R, Solana R (2015) Immunosenescence: implications for response to infection and vaccination in older people. Maturitas 82:50PubMedCrossRefGoogle Scholar
  105. Pereira M, Traverse M, Barros D, Bianchini A, Martinez P (2003) The effects of aging on leukocyte glucocorticoid receptor concentration and response to dexamethasone in dogs. Exp Gerontol 38:989–995PubMedCrossRefGoogle Scholar
  106. Petersen LE, Grassi-Oliveira R, Siara T, Dos Santos SG, Ilha M, De Nardi T, Keisermann M, Bauer ME (2015) Premature immunosenescence is associated with memory dysfunction in rheumatoid arthritis. Neuroimmunomodulation 22:130–137PubMedCrossRefGoogle Scholar
  107. Piani A, Brotini S, Dolso P, Budai R, Gigli GL (2004) Sleep disturbances in elderly: a subjective evaluation over 65. Arch Gerontol Geriatr 9(Suppl):325–331CrossRefGoogle Scholar
  108. Picard D, Khursheed B, Garabedian MJ, Fortin MG, Lindquist S, Yamamoto KR (1990) Reduced levels of hsp90 compromise steroid receptor action in vivo. Nature 348:166–168PubMedCrossRefGoogle Scholar
  109. Popp J, Wolfsgruber S, Heuser I, Peters O, Hull M, Schroder J, Moller HJ, Lewczuk P, Schneider A, Jahn H, Luckhaus C, Perneczky R, Frolich L, Wagner M, Maier W, Wiltfang J, Kornhuber J, Jessen F (2015) Cerebrospinal fluid cortisol and clinical disease progression in MCI and dementia of Alzheimer’s type. Neurobiol Aging 36:601–607PubMedCrossRefGoogle Scholar
  110. Potestio M, Pawelec G, Di Lorenzo G, Candore G, D’anna C, Gervasi F, Lio D, Tranchida G, Caruso C, Romano GC (1999) Age-related changes in the expression of CD95 (APO1/FAS) on blood lymphocytes. Exp Gerontol 34:659–673PubMedCrossRefGoogle Scholar
  111. Radak Z, Chung HY, Koltai E, Taylor AW, Goto S (2008) Exercise, oxidative stress and hormesis. Ageing Res Rev 7:34–42PubMedCrossRefGoogle Scholar
  112. Radford DJ, Wang K, Mcnelis JC, Taylor AE, Hechenberger G, Hofmann J, Chahal H, Arlt W, Lord JM (2010) Dehydroepiandrosterone sulfate directly activates protein kinase C-beta to increase human neutrophil superoxide generation. Mol Endocrinol 24:813–821PubMedPubMedCentralCrossRefGoogle Scholar
  113. Ramirez F, Fowell D, Puklavec M, Simmonds S, Mason D (1996) Glucocorticoids promote a Th2 cytokine response by CD4+ T cells in vitro. J Immunol 156:2406–2412PubMedGoogle Scholar
  114. Raskind M, Peskind E, Wilkinson C (1994) Hypothalamic-pituitary-adrenal axis regulation and human aging. Ann N Y Acad Sci 746:327–335PubMedCrossRefGoogle Scholar
  115. Rattan SI (2006) Theories of biological aging: genes, proteins, and free radicals. Free Radic Res 40:1230–1238PubMedCrossRefGoogle Scholar
  116. Rattan SI (2008) Hormesis in aging. Ageing Res Rev 7:63–78PubMedCrossRefGoogle Scholar
  117. Redinbaugh E, Mccallum R, Kiecolt-Glaser J (1995) Recurrent syndromal depression in caregivers. Psychol Aging 10:358–368PubMedCrossRefGoogle Scholar
  118. Ribeiro F, Lopes RP, Nunes CP, Maito F, Bonorino C, Bauer ME (2007) Dehydroepiandrosterone sulphate enhances IgG and interferon-gamma production during immunization to tuberculosis in young but not aged mice. Biogerontology 8:209–220PubMedCrossRefGoogle Scholar
  119. Rickabaugh TM, Baxter RM, Sehl M, Sinsheimer JS, Hultin PM, Hultin LE, Quach A, Martinez-Maza O, Horvath S, Vilain E, Jamieson BD (2015) Acceleration of age-associated methylation patterns in HIV-1-infected adults. PLoS One 10:e0119201PubMedPubMedCentralCrossRefGoogle Scholar
  120. Rohleder N, Kudielka BM, Hellhammer DH, Wolf JM, Kirschbaum C (2002) Age and sex steroid-related changes in glucocorticoid sensitivity of pro-inflammatory cytokine production after psychosocial stress. J Neuroimmunol 126:69–77PubMedCrossRefGoogle Scholar
  121. Rohleder N, Wolf JM, Kirschbaum C (2003) Glucocorticoid sensitivity in humans-interindividual differences and acute stress effects. Stress 6:207–222PubMedCrossRefGoogle Scholar
  122. Ruan Q, Qian F, Yu Z (2014) Effects of polymorphisms in immunity-related genes on the immune system and successful aging. Curr Opin Immunol 29:49–55PubMedCrossRefGoogle Scholar
  123. Sakakura Y, Nakagawa Y, Ohzeki T (2006) Differential effect of DHEA on mitogen-induced proliferation of T and B lymphocytes. J Steroid Biochem Mol Biol 99:115–120PubMedCrossRefGoogle Scholar
  124. Salehian MB, Kejriwal MK (1999) Glucocorticoid-induced muscle atrophy: mechanisms and therapeutic strategies. Endocr Pract 5:277–281PubMedCrossRefGoogle Scholar
  125. Sanchis-Gomar F, Garcia-Gimenez JL, Perez-Quilis C, Gomez-Cabrera MC, Pallardo FV, Lippi G (2012) Physical exercise as an epigenetic modulator. Eustress, the “positive stress” as an effector of gene expression. J Strength Cond Res 26:3469PubMedCrossRefGoogle Scholar
  126. Sapolsky RM, Krey LC, Mcewen BS (1986) The neuroendocrinology of stress and aging: the glucocorticoid cascade hypothesis. Endocr Rev 7:284–301PubMedCrossRefGoogle Scholar
  127. Sapolsky RM, Romero LM, Munck AU (2000) How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions. Endocr Rev 21:55–89PubMedGoogle Scholar
  128. Sawalha AH, Kovats S (2008) Dehydroepiandrosterone in systemic lupus erythematosus. Curr Rheumatol Rep 10:286–291PubMedPubMedCentralCrossRefGoogle Scholar
  129. Schiepers OJ, Wichers MC, Maes M (2005) Cytokines and major depression. Prog Neuro-Psychopharmacol Biol Psychiatry 29:201–217CrossRefGoogle Scholar
  130. Schmidt M, Lugering N, Lugering A, Pauels HG, Schulze-Osthoff K, Domschke W, Kucharzik T (2001) Role of the CD95/CD95 ligand system in glucocorticoid-induced monocyte apoptosis. J Immunol 166:1344–1351PubMedCrossRefGoogle Scholar
  131. Schnittger RI, Walsh CD, Casey AM, Wherton JP, Mchugh JE, Lawlor BA (2012) Psychological distress as a key component of psychosocial functioning in community-dwelling older people. Aging Ment Health 16:199–207PubMedCrossRefGoogle Scholar
  132. Schulz R, Beach SR (1999) Caregiving as a risk factor for mortality: the Caregiver Health Effects Study. JAMA 282:2215–2219PubMedCrossRefPubMedCentralGoogle Scholar
  133. Schulz R, O’brien A, Czaja S, Ory M, Norris R, Martire LM, Belle SH, Burgio L, Gitlin L, Coon D, Burns R, Gallagher-Thompson D, Stevens A (2002) Dementia caregiver intervention research: in search of clinical significance. Gerontologist 42:589–602PubMedPubMedCentralCrossRefGoogle Scholar
  134. Schwab R, Szabo P, Manavalan JS, Weksler ME, Posnett DN, Pannetier C, Kourilsky P, Even J (1997) Expanded CD4+ and CD8+ T cell clones in elderly humans. J Immunol 158:4493–4499PubMedGoogle Scholar
  135. Selye H (1936) Syndrome produced by diverse nocuous agents. Nature 138:32CrossRefGoogle Scholar
  136. Shaw WS, Patterson TL, Ziegler MG, Dimsdale JE, Semple SJ, Grant I (1999) Accelerated risk of hypertensive blood pressure recordings among Alzheimer caregivers. J Psychosom Res 46:215–227PubMedCrossRefGoogle Scholar
  137. Silva C, Powell-Oliver F, Jewell C, Sar M, Allgood V, Cidlowski J (1994) Regulation of the human glucocorticoid receptor by long-term and chronic treatment with glucocorticoid. Steroids 59:436–442PubMedCrossRefGoogle Scholar
  138. Sippell WG, Becker H, Versmold HT, Bidlingmaier F, Knorr D (1978) Longitudinal studies of plasma aldosterone, corticosterone, deoxycorticosterone, progesterone, 17-hydroxyprogesterone, cortisol, and cortisone determined simultaneously in mother and child at birth and during the early neonatal period. I. Spontaneous delivery. J Clin Endocrinol Metab 46:971–985PubMedCrossRefGoogle Scholar
  139. Solerte SB, Fioravanti M, Vignati G, Giustina A, Cravello L, Ferrari E (1999) Dehydroepiandrosterone sulfate enhances natural killer cell cytotoxicity in humans via locally generated immunoreactive insulin- like growth factor I. J Clin Endocrinol Metab 84:3260–3267PubMedGoogle Scholar
  140. Southam CM, Ehrlich J (1943) Effects of extracts of western red-cedar heartwood on certain wood-decaying fungi in culture. Phytopathology 33:517–524Google Scholar
  141. Souza-Talarico JN, Plusquellec P, Lupien SJ, Fiocco A, Suchecki D (2014) Cross-country differences in basal and stress-induced cortisol secretion in older adults. PLoS One 9:e105968PubMedPubMedCentralCrossRefGoogle Scholar
  142. Spahn J, Szefler S, Surs W, Doherty D, Nimmagadda S, Leung D (1996) A novel action of IL-13: induction of diminished monocyte glucocorticoid receptor-binding affinity. J Immunol 157:2654–2659PubMedGoogle Scholar
  143. Stalder T, Tietze A, Steudte S, Alexander N, Dettenborn L, Kirschbaum C (2014) Elevated hair cortisol levels in chronically stressed dementia caregivers. Psychoneuroendocrinology 47:26–30PubMedCrossRefGoogle Scholar
  144. Starkman M, Schteingart D, Schork M (1981) Depressed mood and other psychiatric manifestations of Cushing’s syndrome: relationship to hormone levels. Psychosom Med 43:3–18PubMedCrossRefGoogle Scholar
  145. Sternberg E (2002) Neuroendocrine regulation of autoimmune/inflammatory disease. J Endocrinol 169:429–435CrossRefGoogle Scholar
  146. Stone AA, Schwartz JE, Broderick JE, Deaton A (2010) A snapshot of the age distribution of psychological well-being in the United States. Proc Natl Acad Sci U S A 107:9985–9990PubMedPubMedCentralCrossRefGoogle Scholar
  147. Straub RH, Konecna L, Hrach S, Rothe G, Kreutz M, Scholmerich J, Falk W, Lang B (1998) Serum dehydroepiandrosterone (DHEA) and DHEA sulfate are negatively correlated with serum interleukin-6 (IL-6), and DHEA inhibits IL-6 secretion from mononuclear cells in man in vitro: possible link between endocrinosenescence and immunosenescence. J Clin Endocrinol Metab 83:2012–2017PubMedCrossRefGoogle Scholar
  148. Straub R, Miller L, Scholmerich J, Zietz B (2000) Cytokines and hormones as possible links between endocrinosenescence and immunosenescence. J Neuroimmunol 109:10–15PubMedCrossRefGoogle Scholar
  149. Suzuki T, Suzuki N, Daynes R, Engleman E (1991) Dehydroepiandrosterone enhances IL2 production and cytotoxic effector function of human T cells. Clin Immunol Immunopathol 61:202–211PubMedCrossRefGoogle Scholar
  150. Tamura Y, Okinaga H, Takami H (2004) Glucocorticoid-induced osteoporosis. Biomed Pharmacother 58:500–504PubMedCrossRefGoogle Scholar
  151. Tan XD, Dou YC, Shi CW, Duan RS, Sun RP (2009) Administration of dehydroepiandrosterone ameliorates experimental autoimmune neuritis in Lewis rats. J Neuroimmunol 207:39–44PubMedCrossRefGoogle Scholar
  152. Truckenmiller ME, Princiotta MF, Norbury CC, Bonneau RH (2005) Corticosterone impairs MHC class I antigen presentation by dendritic cells via reduction of peptide generation. J Neuroimmunol 160:48–60PubMedCrossRefGoogle Scholar
  153. Trzonkowski P, Mysliwska J, Godlewska B, Szmit E, Lukaszuk K, Wieckiewicz J, Brydak L, Machala M, Landowski J, Mysliwski A (2004) Immune consequences of the spontaneous pro-inflammatory status in depressed elderly patients. Brain Behav Immun 18:135–148PubMedCrossRefGoogle Scholar
  154. Trzonkowski P, Szmit E, Mysliwska J, Mysliwski A (2006) CD4+CD25+ T regulatory cells inhibit cytotoxic activity of CTL and NK cells in humans-impact of immunosenescence. Clin Immunol 119:307–316PubMedCrossRefGoogle Scholar
  155. Van Cauter E, Leproult R, Kupfer DJ (1996) Effects of gender and age on the levels and circadian rhythmicity of plasma cortisol. J Clin Endocrinol Metab 81:2468–2473PubMedGoogle Scholar
  156. Vedhara K, Cox N, Wilcock G, Perks P, Lightman S, Shanks N (1999) Chronic stress in elderly carers of dementia patients and antibody response to influenza vaccination. Lancet 353:627–631PubMedCrossRefGoogle Scholar
  157. Vitaliano PP, Scanlan JM, Zhang J, Savage MV, Hirsch IB, Siegler IC (2002) A path model of chronic stress, the metabolic syndrome, and coronary heart disease. Psychosom Med 64:418–435PubMedCrossRefGoogle Scholar
  158. Weyand CM, Yang Z, Goronzy JJ (2014) T-cell aging in rheumatoid arthritis. Curr Opin Rheumatol 26:93–100PubMedPubMedCentralCrossRefGoogle Scholar
  159. Yin D, Tuthill D, Mufson RA, Shi Y (2000) Chronic restraint stress promotes lymphocyte apoptosis by modulating CD95 expression. J Exp Med 191:1423–1428PubMedPubMedCentralCrossRefGoogle Scholar
  160. Zhang TY, Ding X, Daynes RA (2005) The expression of 11 beta-hydroxysteroid dehydrogenase type I by lymphocytes provides a novel means for intracrine regulation of glucocorticoid activities. J Immunol 174:879–889PubMedCrossRefGoogle Scholar
  161. Zipp F, Wendling U, Beyer M, Grieger U, Waiczies S, Wagenknecht B, Haas J, Weller M (2000) Dual effect of glucocorticoids on apoptosis of human autoreactive and foreign antigen-specific T cells. J Neuroimmunol 110:214–222PubMedCrossRefGoogle Scholar
  162. Zovato S, Simoncini M, Gottardo C, Pratesi C, Vampollo V, Spigariol A (1996) Dexamethasone suppression test: corticosteroid receptors regulation in mononuclear leukocytes of young and aged subjects. Aging Clin Exp Res 8:360–364CrossRefGoogle Scholar
  163. Zunszain PA, Anacker C, Cattaneo A, Carvalho LA, Pariante CM (2011) Glucocorticoids, cytokines and brain abnormalities in depression. Prog Neuro-Psychopharmacol Biol Psychiatry 35:722–729CrossRefGoogle Scholar
  164. Zuppa C, Prado CH, Wieck A, Zaparte A, Barbosa A, Bauer ME (2015) Acupuncture for sleep quality, BDNF levels and immunosenescence: a randomized controlled study. Neurosci Lett 587:35–40PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  1. 1.Laboratory of Stress Immunology, School of SciencesPontifical Catholic University of the Rio Grande do SulPorto AlegreBrazil

Personalised recommendations