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Intervention in the aging immune system: Influence of dietary restriction, dehydroepiandrosterone, melatonin, and exercise

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Abstract

The decline in immunologic function with age is associated with an increase in susceptibility to infections and the occurrence of autoimmune diseases and cancers. Hence, the restoration of immunologic function is expected to have a beneficial effect in reducing pathology and maintaining a healthy condition in advanced age. A number of therapeutic strategies have been employed to intervene in the aging immune system. This article reviews the effect of dietary restriction (DR), dehydroepiandrosterone (DHEA) treatment, melatonin (MLT) therapy, and exercise on modulating the immune responses and retarding/reducing immunosenescence. DR has been subject to intensive research and is known to be the most efficacious means of increasing longevity, reducing pathology and enhancing immune function.

The circulatory levels of the androgenic hormone DHEA and the pineal hormone MLT decrease with increasing age, and this decrease has been correlated with the age-related decline in the immune system. Therefore, the observation that immunosenescence is associated with low levels of DHEA and MLT has provided a rationale for therapeutic intervention. DHEA treatment and MLT therapy both exhibit immunostimulatory actions and preliminary reports indicate that hormonal (DHEA or MLT) substitution therapy reverses immunosenescence in mice. Similarly, exercise in some studies has been shown to enhance the immune response. However, these findings have not been confirmed by other laboratories. Thus, at the present time, it is difficult to draw any definitive conclusions on the efficacy of DHEA, MLT, and exercise on reversing or restoring the aging immune system.

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References

  1. Makinodan, T. and Kay, MB.: Age influence on the immune system. Adv. Immunol., 29:287–296, 1980.

    PubMed  CAS  Google Scholar 

  2. Pahlavani, M.A.: Immunological aspects of aging. Drugs of Today, 23:611–624, 1987.

    Google Scholar 

  3. Thoman, M. L. and Weigle, W.O.: The Cellular and Subcellular Bases of Immunosenescence. Adv. Immunol., 46:221–237, 1987.

    Google Scholar 

  4. Murasko, D. M. and Goonewardene, I.M: T-Cell Function in Aging: Mechanisms of Decline. Ann. Rev. Gerontol., 10:71–88, 1990.

    CAS  Google Scholar 

  5. Miller, R.A.: Aging and immune function. Int. Rev. Cytol., 124:187–193, 1991.

    PubMed  CAS  Google Scholar 

  6. Hirokawa, K.: Autoimmunity and Aging. In J.M. Cruse and R.E.J. Lewis (eds.), Autoimmunity: Basic Concepts: Systemic and Selected OrganSpecific Diseases, Karger, Basel, pp. 251–288, 1985.

    Google Scholar 

  7. Hirokawa, K.: Aging and the immune system. In A.M. Kligman and Y. Takase (eds.), Cutaneous Aging, University of Tokyo Press, pp. 61–78, 1988.

  8. Walford, R. L.: Immunologic theory of aging: Current status. FASEB J., 33:2020., 1974.

    CAS  Google Scholar 

  9. Fabris, N., Pierpaoli, W., and Sorkin, E.: Lymphocytes, Hormones, and Aging. Nature, 240:557–559, 1972.

    Article  PubMed  CAS  Google Scholar 

  10. Hirokawa, K., Sato, K., and Makinodan, T.: Restoration of impaired immune function in aging animals. V. Long-term immunopotentiating effects of combined young bone marrow and new born thymusgrafts. Clin. Immunol. Immunopathol., 22: 297–304, 1982.

    Article  PubMed  CAS  Google Scholar 

  11. Astle, C.M. and Harrison, D.E.: Effects of marrow donor and recipient age on immune responses. J. Immunol., 132:673–677, 1984.

    PubMed  CAS  Google Scholar 

  12. Hirokawa, K.: Reversing and restoring immune functions. Mech. Ageing Dev., 93:119–124, 1997.

    Article  PubMed  CAS  Google Scholar 

  13. Pahlavani, M.A. and Richardson, A.: The effect of age on the expression of interleukin-2. Mech. Ageing Dev., 89:125–154, 1996.

    Article  PubMed  CAS  Google Scholar 

  14. Effros, R.B., Casillas, A., and Walford, R.L.: The effect of thymosin on immunity to influenza in aged mice. Aging Immunol. Infect. Dis., 1:31–40, 1988.

    Google Scholar 

  15. Goso, C., Frasca, D., and Doria, D.: Effect of synthetic thymic humoral factor (THF-γ2) on T cell activities in immunodeficient aging mice. Clin. Exp. Immunol., 87:346–351, 1992.

    Article  PubMed  CAS  Google Scholar 

  16. Daynes RA, Araneo BA.: Prevention and reversal of some age-associated changes in immunologic responses by supplemental dehydroepiandrosterone sulfate therapy. Aging: Immunol. & Infect. Dis., 3:135–153., 1992.

    Google Scholar 

  17. Araneo BA, Woods ML, II, Daynes RA.: 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: 830–840, 1993.

    PubMed  CAS  Google Scholar 

  18. Maestroni, G.J, Conti, A., and Pierpaoli, W.: Pineal melatonin, its fundamental immunoregulatory role in aging and cancer. Ann. Ny. Acad. Sci., 521:140–148, 1988.

    PubMed  CAS  Google Scholar 

  19. Caroleo, MC., Frasca, D., Nisticok, G, and Doria, G.: Melatonin as immunomodulator in immunodeficient mice. Immunopharmacol., 23:81–89, 1992.

    Article  CAS  Google Scholar 

  20. Weindruch, R. H., Kriste, J.A., Naeim, F., Mullen, B.G., and Walford, R.L.: Influence of weaning-initiated dietary restriction on responses of T cell mitogens and on splenic T cell levels in a long-lived F1-hybrid mouse strain. Exp. Gerontol., 17:49–64, 1982.

    Article  PubMed  CAS  Google Scholar 

  21. Fernandes, G.: Nutritional Factors: Modulating effects on immune function and aging. Pharmacol. Rev., 36:123S-129S, 1984.

    Google Scholar 

  22. Pahlavani, M.A., Cheung, H.T., Chesky, J.A. and Richardson, A.: Influence of exercise on the immune function of rats of various ages. J. Appl. Physiol., 64:1997–2001, 1988.

    PubMed  CAS  Google Scholar 

  23. Nasrullah, I. and Mazzeo, R.S.: Age-related immunosenescence in Fischer 344 rats: Influence of exercise training. J. Appl. Physiol., 73:1932–1938, 1992.

    PubMed  CAS  Google Scholar 

  24. Venkatraman, J.T., and Fernandes, G.: Exercise, immunity and aging. Aging Clin. Exp., 9:4256, 1997.

    Google Scholar 

  25. Chandra, R.K.: Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet, 340:1124–1127, 1992.

    Article  PubMed  CAS  Google Scholar 

  26. Bogden, J.D., Bendich, A., Kemp, F.W., Bruening, K.S., Shurnick, J.H., Denny, T., Baker, H., and Louria, D.B.: Daily micronutrient supplements enhance delayed hypersensitivity skin test responses in older people. Am. J. Clin. Nutr., 60:437–447, 1994.

    PubMed  CAS  Google Scholar 

  27. Meydani, S.N., Meydani, M., Blumberg, J.B., Leka, L.S., Siber, G., Loszewski, R., Thompson, C., Pedrosa, M.C., Diamond, R.D., and Stollar, B.D.: Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. JAMA 277:1380–1386, 1997.

    Article  PubMed  CAS  Google Scholar 

  28. Masoro, E. J., Shimokawa, I., Higami, Y., McMahan, C. A. and Yu, B.P.: Temporal pattern of food restriction not a factor in the restoration of aging process by dietary restriction. J. Gerontol., 50:B48–B53, 1995.

    Google Scholar 

  29. Richardson A.: The effect of age and nutrition on protein synthesis by cells and tissues from mammals, in CRC Handbook of Nutrition and Aging. Watson, R.R., Ed., CRC Press, Boca Ration, FL, 31, 1985.

    Google Scholar 

  30. Weindruch, R.H., Kriste, J.A., Cheney, K.E., and Walford, R.L.: Influence of controlled dietary restriction on immunologic function and aging. Fed. Proc., 38:2007–2016, 1979.

    PubMed  CAS  Google Scholar 

  31. Regelson, W., Loria, R., and Kalami, M.: Dehydroepiandrosterone (DHEA)-the “Mother Steroid”. I. Immunologic action. Ann. N. Y. Acad. Sci., 719, 553–563, 1994.

    PubMed  CAS  Google Scholar 

  32. Regelson, W., Kalimi, M., and Loda, R.: DHEA: some thoughts as to its biologic and clinical action. In: Kalimi M, Regelson W. eds. The Biologic role of Dehydroepi-androsterone (DHEA). Walter de Guyter: New York, pp. 405–445, 1990.

    Google Scholar 

  33. Maestroni, G.J, Conti, A., and Pierpaoli, W.: Pineal melatonin, its fundamental immunoregulatory role in aging and cancer. Ann. Ny. Acad. Sci., 1988, 521:140–148, 1988.

    PubMed  CAS  Google Scholar 

  34. Maestroni, G., and Conti, A.: Melatonin and the immune-hematopoietic system. Theapeuric and adverse pharmacological correlates. Neuro-immunomodulation, 3:325–332, 1996.

    CAS  Google Scholar 

  35. McCay, C. M., Crowell, M.F., and Maynard, L.A.: The effect of retarded growth upon the length of life span and upon the ultimate body size. J. Nutr., 10:63–72, 1935.

    CAS  Google Scholar 

  36. Masoro, E. J. and McCarter, R.M.: Dietary Restriction as a Probe of Mechanisms of Senescence. Ann. Rev. Gerontol., Chapter 11:183–194, 1990.

    Google Scholar 

  37. Masoro, E. J.: Potential role of modulation of fuel use in the antiaging action of dietary restriction. Ann. NY Acad. Sci., 663:403–411, 1992.

    PubMed  CAS  Google Scholar 

  38. Gerbase-Delima, M., R. K. Liu, K. E. Cheney, R. Mickey, and Walford, R.L.: Immune function and survival in the long-lived mouse strain subjected to undernutrition. Gerontologia, 21:184–193, 1975.

    PubMed  CAS  Google Scholar 

  39. Fernandes, G., E. Yunis, J., and Good, R.A.: Influence of protein restriction on immune function in NZB mice. J. Immunol., 116:782–788, 1976.

    PubMed  CAS  Google Scholar 

  40. Venkatraman, J. and Fernandes, G.: Modulation of age-related alterations in membrane composition and receptor-associated immune functions by food restriction in Fischer 344 rats. Mech. Ageing Dev., 63:27–44, 1992.

    Article  PubMed  CAS  Google Scholar 

  41. Miller, R. A.: Caloric restriction and immune function: developmental mechanisms. Aging Clin. Exp. Res., 3:395–403, 1991.

    CAS  Google Scholar 

  42. Gilman-Sachs, A., Kim, Y.B., Pollard, M., and Snyder, L.D.: Influence of Aging, Environmental Antigens, and Dietary Restriction on Expression of Lymphocyte Subsets in Germ-free and Conventional Lobund-Wistar Rats. J. Gerontol., 46: B101–B109, 1991.

    PubMed  CAS  Google Scholar 

  43. Pahlavani, M. A., Cheung, H.T., Cai, N.S., and Richardson, A.: Influence of dietary restriction and aging and gene expression in the immune system of rats. In Biomedical advances in aging. A.L. Goldstein, ed. Plenum Publishing Corp., New York, p. 259–270, 1990.

    Google Scholar 

  44. Lindquist, S.: The heat-shock response. Ann. Rev. Biochem., 55:1151–1191, 1986.

    Article  PubMed  CAS  Google Scholar 

  45. Lindquist, S., Craig, E.A.: The heat-shock proteins. Ann. Rev.Genet., 22:631–677, 1988.

    Article  PubMed  CAS  Google Scholar 

  46. Young, D.B.: Heat shock proteins: Immunity and Autoimmunity. (review). Current Opinion in Immunology, 4: 396–400, 1992.

    PubMed  CAS  Google Scholar 

  47. Sribvastava, P.K., Udono, H., Blachere, N.E., and Li, Z.: Heat shock proteins transfer peptides during antigen processing and CLT priming (review). Immunogenetics, 39:93–98, 1994.

    Google Scholar 

  48. Pahlavani, M.A., Harris, M.D., Moore, S.A., and Richardson, A.: Expression of heat shock protein 70 in rat spleen lymphocytes is affected by age but not by food restriction. N. Nutr., 126:2060–2075, 1996.

    Google Scholar 

  49. Byun, D.S., Venkartramann, J.T., Yu, B.P., and Fernandes, G.: Modulation of antioxidant activities and immune response by food restriction in aging Fischer 344 rats. Aging Clin. Exp., Res., 7:40–48, 1995.

    CAS  Google Scholar 

  50. Chayoth, R., Christou, N.V., Nohr, C.W., Yale, J.F., Poussier, P., Grose, M., Montambault, M., Chan, W., and Marliss, E.B.: Immunological responses to chronic heat exposure and food restriction in rats. Am. J. Clin. Nutr., 48:361–367, 1988.

    PubMed  CAS  Google Scholar 

  51. Goonewardene, IM. and Murasko, D.M.: Age-associated changes in mitogen-induced lympho-proliferation and lymphokine production in the long-lived Brown-Norway rat: Effect of caloric restriction. Mech. Ageing Dev., 83: 103–116, 1995.

    Article  PubMed  CAS  Google Scholar 

  52. Konno, A., Utsuyama, M., Kurashima, C., Kasai, M., Kimmura, S., and Hirokawa, K.: Effects of a protein-free diet or food restriction on the immune system of Wistar and Buffalo rats at different ages. Mech. Ageing and Dev., 72:183–197, 1993.

    Article  CAS  Google Scholar 

  53. Pieri, C., Rechioni, R., and Moroni, F.: Food restriction in female Wistar rats. VI. Effect of reduced glutathione on the proliferative response of splenic lymphocytes from ad libitum fed and food restricted animals. Arch. Gerontol. Geriatr., 16:81–92, 1993.

    Article  PubMed  CAS  Google Scholar 

  54. Iwai, H. and Fernandes, G.: Immunological functions in food-restricted rats: enhanced expression of high-affinity interleukin-2 receptors on splenic T cells. Immunol. Lett., 23:125–132, 1990.

    Article  Google Scholar 

  55. Fernandes, G., Venkatraman, J., Khare, A., Horbach, G.J., and Friedrichs, W.: Modulation of gene expression in autoimmune disease and aging by food restriction and dietary lipids. Proc. Soc. Exp. Biol. Med., 193:16–25, 1990.

    PubMed  CAS  Google Scholar 

  56. Pahlavani, M.A. Harris, M.D., and Richardson, A.: The increase in the induction of IL-2 expression with caloric restriction is correlated to changes in the transcription factor NFAT. Cell. Immunol., 180:10–19, 1997.

    Article  PubMed  CAS  Google Scholar 

  57. Hishinuma, K., Nishimura, T., Konno, A., Hashimoto, Y., and Kimura, S.: The effect of dietary restriction on mouse T cell functions. Immunol. Lett., 17:351–359, 1988.

    Article  PubMed  CAS  Google Scholar 

  58. Weindruch, R. H., Kriste, J.A., Naeim, F., Mullen, B.G., and Walford, R.L.: Influence of weaning-initiated dietary restriction on responses of T cell mitogens and on splenic T cell levels in a long-lived F1-hybrid mouse strain. Exp. Gerontol., 17:49–64, 1982.

    Article  PubMed  CAS  Google Scholar 

  59. Weindruch, R.H., Kriste, J.A., Cheney, K.E., and Walford, R.L.: Influence of controlled dietary restriction on immunologic function and aging. Fed. Proc., 38:2007–2016, 1979.

    PubMed  CAS  Google Scholar 

  60. Weindruch, R., Devens, B.H., Raft, H.V., and Walford, R.L.: Influence of dietary restriction and aging on natural killer cell activity in mice. J. Immunol., 130:993–996, 1983.

    PubMed  CAS  Google Scholar 

  61. Grossmann, A., Price, L., Jinneman, J.C., Wolf, N.S., and Rabinovitch, P.S.: The effect of long-term caloric restriction on function of T cell subsets in old mice. Cell. Immunol., 131:191–204, 1990.

    Article  PubMed  CAS  Google Scholar 

  62. Cheney, K.E., Liu, R.K., Smith, G.S., Meredith, P.J., Michey, M.R., Walford, R.L.: The effect of dietary restriction of varying duration on survival, tumor patterns, immune function, and body temperature in B10C3F1 female mice. J. Gerontol., 38:420–430, 1983.

    PubMed  CAS  Google Scholar 

  63. Venkatraman, J., Attwood, V.G., Turturro, A., Hart, R.W., and Fernandes, G.: Maintenance of virgin T cells and immune function by food restriction during aging in ling-lived B6D2F1 female mice. Aging: Immunol. Infec. Dis., 5:13–25, 1994.

    Google Scholar 

  64. Fernandes, G.: Nurtritional Factors: Modulating Effects on Immune Function and Aging. Pharmacol. Rev., 36:123S–129S., 1984.

    PubMed  CAS  Google Scholar 

  65. Kubo, C., Johnson, B.C., Day, N.K., and Good, R.A.: Calorie Source, Calorie Restriction, Immunity and Aging of (NZB/NZW)F1 mice. J. Nutr., 114:1884–1899, 1984.

    PubMed  CAS  Google Scholar 

  66. Fernandes, G., Friend, P., Yunis, E.J., and Good, R.A.: Influence of dietary restriction on immunological function and renal disease in (NZBXNZW)F1 mice. Proc. Natl. Acad. Sci. USA, 75:1500–1504, 1978.

    PubMed  CAS  Google Scholar 

  67. Jung, L.K., Palladino, M.A., Calvano, S., Mark, D.A., Good, R.A., and Fernandes, G.: Effect of calorie restriction on the production and responsiveness to interleukin-2 in (NZB/NZX)F1 mice. Clin. Immunol., Immunopharmacol., 25:295–301, 1982.

    Article  CAS  Google Scholar 

  68. Ellis, M.: An introduction to transcription. In Genes and Cancer. D. Carney and K. Sikora, eds. John Wiley and Sons, Chichester, UK, p. 107–118, 1990.

    Google Scholar 

  69. Angel, P., Allegretto, E.A., Okino, S.T., Hattari, K., Boyle, W.J., Hunter, T., and Karin, M.: Oncogene jun encodes a sequence-specific trans-activator similar to AP-1. Nature, 332:166–168, 1988.

    Article  PubMed  CAS  Google Scholar 

  70. Mitchell, P. J. and Tjian, R.: Transcriptional regulation in mammalian cells by sequence-pecific DNA binding proteins. Science, 245:371–373, 1989.

    PubMed  CAS  Google Scholar 

  71. Ullman, K. S., Northrop, J.P., Verweij, C.L., and Crabtree, G.R.: Transmission of Signals from the T Lymphocyte Antigen Receptor to the Genes Responsible for Cell Proliferation and Immune Function: The Missing Link. Annu. Rev. Immunol., 8:421–443, 1990.

    Article  PubMed  CAS  Google Scholar 

  72. Riegel, J. S., Corthesy, B., Flanagan, W.M., and Crabtree, G.R.: Regulation of the Interleukin-2 Gene. Chem. Immunol., 51:266–287, 1992.

    Article  PubMed  CAS  Google Scholar 

  73. Regelson, W., and Kalami, M.: Dehydro-epiandrosterone (DHEA) — the Multifunctional Steroid. II. Effect on the CNS, cell proliferation, metabolic and vascular, clinical and other effects. Mechanism of Action. Ann. N. Y. Acad. Sci., 719, 564–575, 1994.

    PubMed  CAS  Google Scholar 

  74. Schwartz, A.G.: Inhibition of spontaneous breast cancer formation in female (C3H-Avy/A) mice by long term treatment with dehydroepiandrosterone. Cancer Res., 39:1129–1132, 1979.

    PubMed  CAS  Google Scholar 

  75. Parker C.R, and Schuster, M.W: Effects of syphilis infection on adrenocortical function in man. Proc. Soc. Exp. Biol. Med., 197:165–167, 1991.

    PubMed  Google Scholar 

  76. Moolenar, A.J., Van Seters, A.P.: Gas-chromatographic determination of steroids in the urine of patients with Cushing’s syndrome. Acta Endocrinology (Copenhagen), 67:303–315, 1971.

    Google Scholar 

  77. Keutman, E.H., Mason W.B.: Individual urinary 17-ketosteroids of healthy persons determined by gas-chromatograph-biochemical and clinical consideration. J. Clin. Endocrinol., 27:406–420, 1967.

    Google Scholar 

  78. Loria, R.M., Inge, T.H., Cook, S.: Protection against acute lethal viral infections with the native steroid dehydroepiandrosterone (DHEA). J. Med, Virol., 26: 301–314, 1988.

    CAS  Google Scholar 

  79. Loria, R.M., Regelson, W., Padget, D.A.: Immune response facilitation and resistance to viral and bacterial infections with DHEA. In: The Biologic Role of Dehydroepiandrosterone (DHEA). Kalimi, M., Regelson, W. (Eds.). Walter de Gruyter, New York, pp. 107–130, 1990.

    Google Scholar 

  80. Ben-Nathan D, Feuerstein G.: The influence of cold and isolation stress on resistance of mice to West Nile virus encephalitis. Experientia, 46:285–290, 1990.

    Article  PubMed  CAS  Google Scholar 

  81. Rasmussen, D.R., Martin, E.G., Arrowood, M.J.: Effect of dexamethasone and dehydroepiandrosterone in immunosuppressed rats infected with Crytosporidiumparvum. J. Protozool., 38:157–159, 1991.

    Google Scholar 

  82. Araneo, B.A., Shelby, J., Li, G.Z.: Administration of dehydroepiandrosterone to burned mice preserves normal immunologic competence. Arch. Surg., 128: 318–325, 1993.

    PubMed  CAS  Google Scholar 

  83. Daynes, R.A., Dudley, D.J., Araneo, B.A.: Regulation of murine lymphokine production in vivo. II. Dehydroepiandrosterone is a natural enhancer of IL-2 synthesis by helper T-cells. Eur. J. Immunol., 20: 793–801, 1990.

    PubMed  CAS  Google Scholar 

  84. Padgett, D.A. and Loria, R.M.: In vitro potentiation of lymphocyte activation by dehydroepiandrosterone, androstenediol, and androstenetriol. J. Immunol., 153: 1544–1552, 1994.

    PubMed  CAS  Google Scholar 

  85. Risdon, G., Cope, J., and Bennett, M: Mechanisms of chemoprevention by dietary dehydroepiandrosterone: Inhibition of lymphopoiesis. Am. J. Pathol., 136:759–769, 1990.

    PubMed  CAS  Google Scholar 

  86. Pahlavani, M.A. and Harris, M.D.: Effect of dehydroepiandrosterone on mitogen-induced lymphocyte proliferation and cytokine production in young and old F344 rats. Immunol. Lett., 47:9–14, 1995.

    Article  PubMed  CAS  Google Scholar 

  87. Blauer, K.L, Poth, M., Rogers, W.M., and Bernton, E.W.: Dehydroepiandrosterone antagonizes the suppressive effects of dexamethasone on lymphocyte proliferation. Endocrinol., 129:3174–3179, 1991.

    CAS  Google Scholar 

  88. Risdon, G.: Differential effects of DHEA on murine lymphopoiesis and myelopoiesis. Exp. Hematol., 19: 128–131, 1991.

    PubMed  CAS  Google Scholar 

  89. Matsunaga, A., Miller, B.C., Cottam, G.L.: Dehydroepiandrosterone prevention of autoimmune disease in NZB/WF1 mice: lack of an effect on associated immunological abnormaqities. Biochem. Biophys. Acta., 992: 265–271, 1989.

    PubMed  CAS  Google Scholar 

  90. Risdon, G., Cope, J., and Bennett, M.: Mechanisms of chemoprevention by dietary dehydroepiandrosterone: Inhibition of lymphopoiesis. Am. J. Pathol., 136:759–769, 1990.

    PubMed  CAS  Google Scholar 

  91. Araneo, B.A., Dowell, T., Diegel, M., and Daynes, R.A.: Dehydroepiandrosterone exerts a depressive influence on the production of interleukin-4 (IL-4), IL-5, and interferon-gamma, but no IL-2 by activated murine T cells. Blood, 78:688–699, 1991.

    PubMed  CAS  Google Scholar 

  92. Garg, M. and Bonada, S.: Reversal of age-associated decline in immune response to Pnu-Immune Vaccine by supplementation with the steroid hormone dehydroepiandrosterone. Infec. & Immunol., 61:2238–2241, 1993.

    CAS  Google Scholar 

  93. Weinduruch, R., McFeeters, G., and Walford, R.L.: Food intake reduction and immunologic alterations in mice fed dehydroepiandrosterone. Exp. Gerontol., 19:295–304, 1984.

    Google Scholar 

  94. Wiedmeier, S.E., Mu, H., Araneo, B.A., and Daynes, R.A,: Age and microenvironment-associated influences by platelet-derived growth factor on T cell function. J. tmmunol., 152:3417–3425, 1994.

    CAS  Google Scholar 

  95. Daynes, R.A., Araneo, B.A., Ershler, W.B., Maloney, C., Li, G., and Ryu, S.: Altered regulation of IL-6 production with normal aging: Possible linkage to the age-associated decline in dehydroepiandrosterone and its sulfated derivative. J. Immunol., 150:5219–5230, 1993.

    PubMed  CAS  Google Scholar 

  96. May, M., Holmes, E., Rogers, W., and Poth, M.: Protection from glucocorticoid induced thymic involution by dehydroepiandrosterone. Life Science, 46:1627–1631, 1990.

    Article  CAS  Google Scholar 

  97. Dyner, T.S., Lang, W., Geaga, L., Golub, A., Sites, D., Winger, E., Galmarini, M, Masterson, J., and Jacobson, M.A.: An open-label dose-escalation trial of oral dehydroepiandrosterone tolerance and pharmacokinetics in patients with HIV disease. J. Acquired Immune Deficiency Syndromes, 6:459–465, 1993.

    CAS  Google Scholar 

  98. Yang, J., Schwartz, A., and Henderson, E.: Inhibition of HIV-1 latency reactivation by dehydro-epiandrosterone (DHEA) and an analog of DHEA. AIDS Res. and Human Retroviruses, 9:747–754, 1993.

    CAS  Google Scholar 

  99. Suzuki, T., Suzuki, N., Daynes, R.A.: Dehydro-epiandrosterone enhances IL-2 production and cytotoxic effector function of human T-cells. Clin. Immunol. Immunopathol., 61:202–211, 1991.

    PubMed  CAS  Google Scholar 

  100. Khorram, O., Vu, L., and Yen, S.: Activation of immune function by dehydroepiandrosterone (DHEA) in age-advanced men. J. Gerontol., 52A:M1–M7, 1997.

    CAS  Google Scholar 

  101. Maestroni, G.J, Conti, A.: Melatonin in relation to the immune system. In: Yu, H.S., Reiter, R.J. (eds), Melatonin: Biosynthesis, Physiological Effects and Clinical Applications. Boca Raton, CRC Press, pp. 290–306, 1993.

    Google Scholar 

  102. Maestroni, G.J.: The immunoendocrine role of melatonin. J. Pineal. Res., 14:1–10, 1993.

    PubMed  CAS  Google Scholar 

  103. Pahlavani, M.A.: Role of melatonin in immunity, aging, and cancer: therapeutic intervention. Drugs of Today, 22:25–39, 1997.

    Google Scholar 

  104. Maestroni, G.M. and Pierpaoli, W.: Pharmacologic control of the hormonally mediated immune response. In: R. Ader (Ed.) Psychoneuro-immunology. Academic Press, New York, pp. 405–425, 1981.

    Google Scholar 

  105. Maestroni, G.M., Conti, A., and Pierpaoli, W.: Role of the pineal gland in immunity: Circadian synthesis and release of melatonin modulates the antibody response and antagonizes the immunosuppressive effects of corticosterone. J. Neuroimmunol., 13:19–30, 1986.

    Article  PubMed  CAS  Google Scholar 

  106. Caroleo, M.C., Doria, G., and Nistico, G.: Melatonin restores immunodepression in aged and cyclophosphamide-treated mice. Ann. Ny. Acad. Sci., 719:343–352, 1994

    PubMed  CAS  Google Scholar 

  107. Kuci, S., Becker, J., and Veit, G.: Circadian variations of the immunomodulatory role of the pineal gland. Neuroendocrinol., Lett., 10:65–73, 1983.

    Google Scholar 

  108. Becker, J., Veit, G., Handgretinger, R., et al. Circadian variations in the immunomodulatory role of the pineal gland. Neuroendocrinol. Lett., 10:65–72, 1998.

    Google Scholar 

  109. Vermeulen, M., Palermo, M., and Giordano, M.: Neonatal pinealectomy impairs murine antibody-dependent cellular toxicity. J. Neuroimmunol., 43:97–101, 1993.

    Article  PubMed  CAS  Google Scholar 

  110. Del Gobbo, V., Libri, V., Villani, N., Callio, R., and Nistico, G.: Pinealectomy inhibits interleukin-2 production and natural killer activity in mice. Int. J. Immunopharmacol., 11:567–577, 1989.

    Article  PubMed  Google Scholar 

  111. Fraschini, F., Scaglione, F., Franco, P., Demartini, G., Lucini, V., and Stankov, B.: Melatonin and Immunity. Acta. Oncol., 5:775–776, 1990.

    Google Scholar 

  112. Maestroni, G. and Conti, A.: The pineal neurohormone melatonin stimulates activated CD4+, Thy-1+ cells to release opioid agonists with immunoenhancing and anti-stress properties. J. Neuroimmunol., 28:167–176, 1990.

    Article  PubMed  CAS  Google Scholar 

  113. Mocchegiani, E., Bulian, D., Santarelli, L., Tibaldi, A., Muzzioli M., Pierpaoli, W., and Fabris, N.J.: The immuno-reconstituting effect of melatonin orpineal grafting and its relation to zinc pool in aging mice, Neuroimmunol., 53:189–196, 1994.

    Article  CAS  Google Scholar 

  114. Ben-Nathan D., Maestroni, G.M., and Conti, A.: Protective effect of melatonin in mice infected with encephalitis viruses. Arch. Virol., 140:223–230, 1995.

    Article  PubMed  CAS  Google Scholar 

  115. Pierpaoli, W. and Regelson, W.: Pineal control of aging: Effect of melatonin and pineal grafting on aging mice. Proc. Natl. Acad. Sci. USA, 91:787–791, 1994.

    PubMed  CAS  Google Scholar 

  116. Provinciali, M., Stefano, G., Bulian, D., Tibaldi, A., and Fabris, N.: Effect of melatonin and pineal grafting on thymocyte apoptosis in aging mice, Mech. Ageing & Dev., 90:1–9, 1996.

    Article  CAS  Google Scholar 

  117. Maestroni, G.J.: T-helper-2 lymphocytes as a peripheral target of melatonin. J. Pineal Res., 18: 84–89, 1995.

    PubMed  CAS  Google Scholar 

  118. Csaba, G., and Barath, P.: Morphological changes of thymus and the thyroid gland after postnatal extirpation of the pineal body. Endocrinol. Exp., 9:59–67, 1975.

    PubMed  CAS  Google Scholar 

  119. Maestroni, G.J, Conti, A., and Pierpaoli, W.: Role of the pineal gland in immunity. III. Melatonin antagonizes the immunosuppressive effect of acute stress via an opiatergic mechanism, Immunology, 63:465–476, 1988.

    PubMed  CAS  Google Scholar 

  120. Pioli, C., Caroleo, M.C., Nistico, G., and Doria, D.: Melatonin increases antigen presentation and amplifies specific and nonspecific signals for T cell proliferation. Int. J. Immunopharmacol., 15:463–469, 1993.

    Article  PubMed  CAS  Google Scholar 

  121. Sainz, R.M., Mayo, J.C., Urfa, H., Kotler, M., Antolin, A., Fodriguez, C., and Pelaex, A.: The pineal neurohormone melatonin prevents in vivo and in vitro apoptosis in thymocytes. J. Pineal Res., 19:178–188, 1995.

    PubMed  CAS  Google Scholar 

  122. Pahlavani, M.A. and Harris, M.D.: In vitro effects of melatonin on mitogen-induced lymphocyte proliferation and cytokine expression in young and old rats. Immunopharmacol. & Immunotoxicol., 19:327–337, 1997.

    Article  CAS  Google Scholar 

  123. Vaughan, M.K., Hubbard, G.B., Champeny, T.H., Little, J.C., and Reiter, R.J.: Splenic hypertrophy and extramedullary hematopoiesis induced in male Syrian hamsters by short photoperiod or melatonin injections reversed by melatonin pellets or pinealectomy. Am. J. Anat., 179:131–136, 1978.

    Article  Google Scholar 

  124. Morrey, M.K. McLachlan, J.A., Serkin, D.C., and Bakouche, O.: Activation of humanmonocytes by the pineal neurohormone melatonin. J. Immunol., 153:2671–2680, 1994.

    PubMed  CAS  Google Scholar 

  125. Lissoni, P., Pittalis, S., Brivio, F., Tisi, E., Rovetli, F., Ardizzovia A., Barni, S., Tanicini, G., Giudici, G., Biondi, A., Conti, A., and Maestroni, G.: In vitro modulatory effects of interleukin-3 on macrophage activation induced by interleukin-2. Cancer, 71:2976–2981, 1993.

    Google Scholar 

  126. Vijayalaxmia, R., Reiter, R. J., and Meltz, M.L.: Melatonin protects human blood lymphocytes from radiation-induced chromosome damage. Mutation Res., 346:23–31, 1995.

    Article  Google Scholar 

  127. Karasek, M., Liberski, P., Radek, J., and Bartkowiak, J.: Influence of melatonin on the proliferation of hepatoma cells in the Syrian hamster: In vivo and in vitro study, Rovelli, F., Cattaneo, G., Archili, C., and Barni, S.: Serum interleukin-2 levels in relation to the neuroendocrine status in cancer patients. Br. J. Cancer, 62:838–839, 1990.

    Google Scholar 

  128. Das Gupta, T.K.: Influence of pineal gland on the growth and spread of melanoma in hamsters. Cancer Res., 19:83–84, 1968.

    Google Scholar 

  129. Stanberry, L.R., Das Gupta, T.K., and Beattle, C.W.: Photoperiodic control of melanoma growth in hamsters: Influence of pinealectomy and melatonin. Endocrinology, 113:469–475, 1983.

    PubMed  CAS  Google Scholar 

  130. Tamarkin, L., Cohen, M., and Roselle, D.: Melatonin inhibition and pinealectomy enhancement of 7,12-dimethylbenzanthracene induced mammary tumor in therats. Cancer Res 1981, 41:432–436, 1981.

    Google Scholar 

  131. Blask, D.E. and Hill, S. M.: Melatonin and Cancer: Basic and clinical aspects. In: Miles A., Philbrick, D.R., Thompson, C. (Eds.) Melatonin: Clinical Aspects. Oxford University, Oxford U.K, pp. 128–173, 1988.

    Google Scholar 

  132. Lissoni, P., Barni, S., Crispino, S., Tancini, G., and Fraschini, F.: Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur. J. Cancer Clin. Oncol., 25:789–792, 1989.

    Article  PubMed  CAS  Google Scholar 

  133. Conti, A. and Maestroni, G.M.: The clinical neuroimmunotherapeutic role of melatonin in oncology. J. Pineal Res., 10:103–110, 1995.

    Google Scholar 

  134. Lissoni, P., Barni, S., Gazzaniga, M., Ardizzoia, A., Rovelli, F., Brivio, F., and Tancini, G.: Efficacy of the concomitant administration of the pineal hormone melatonin in cancer immunotherapy with low-dose IL-2 in patients with advanced solid tumors who had progressed on IL-2 alone. Oncology, 51:344–347, 1994.

    PubMed  CAS  Google Scholar 

  135. Lissoni, P., Tisi, E., Barni, S.: Biological and clinical results of a neuroimmuno-therapy with IL-2 and the pineal hormone melatonin as a first line treatment inadvanced non-small cell lung cancer. Br. J. Cancer, 66: 155–158, 1992.

    PubMed  CAS  Google Scholar 

  136. Neri, B., Fiorelli, C., Moroni, F.: Modulation of human lymphoblastoid interferon activity by melatonin in metastatic renal cell carcinoma. Cancer, 73:3015–5019, 1994.

    PubMed  CAS  Google Scholar 

  137. Lissoni, P., Barni, S., Ardizzoia, A., Paolorossi, F., Crispino, S.: Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to first-line chemotherapy containing cisplatin. Oncology, 49: 336–339, 1992.

    Article  PubMed  CAS  Google Scholar 

  138. Lissoni, P., Barni, S., Rovelli, F., Brivio, F., Ardizzoia, A., Tancini, G., Conti, A, and Maestroni, G.J: Neuroimmunotherapy of advanced solid neoplasms with single evening subcutaneous injection of low-dose IL-2 and melatonin: Preliminary results. Eur. J. Cancer., 29A:185–189, 1993.

    Article  PubMed  CAS  Google Scholar 

  139. Lissoni, P., Barni, S., Tancini, G.: Immunotherapy with subcutaneous low-dose IL-2 and the pineal indole melatonin as a new effective therapy in advanced cancers of the digestive tract. Br. J. Cancer, 67: 1404–1407, 1993.

    PubMed  CAS  Google Scholar 

  140. Lissoni, P., Brivio, F., Brivio, O., Fumagalli, L., Gramazio, F., Rossi, M:, Emanuelli, G., Alderi, G., and Lavorato, F.: Immune effects of preoperative immunotherapy with high-dose subcutaneous interleukin-2 versus neuroimmunotherapy with low-dose interleukin-2 plus the neurohormone melatonin in gastrointestinal tract tumor patients. J. Biol. Regul. Homeost. Agents, 9:31–33, 1995.

    PubMed  CAS  Google Scholar 

  141. Lissoni, P., Barni, S., Ardizzoia, A., Tancini, G., Conti, A, and G.J. Maestroni, G.M.: A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer, 73:699–701, 1994.

    PubMed  CAS  Google Scholar 

  142. Lissoni, P., Barni, S., Tancini, G., Mainini, E., Piglia, F., and Maestroni, G.M.: Immunoendocrine therapy with low-dose subcutaneous interleukin-2 plus melatonin locally advanced or metastatic endocrine tumors. Oncology, 52:163–166, 1995.

    Article  PubMed  CAS  Google Scholar 

  143. Lissoni, P., Brivio, F., Ardizzoia, A., Tancini, G., and Barni, S.: Subcutaneous therapy with low-dose IL-2 plus neurohormone melatonin in metastatic gastric cancer patients with low performance status. Tumori, 79: 410–404, 1993.

    Google Scholar 

  144. Lissoni, P., Barni, S., Rovelli, F.: Neuroendocrine effects of subcutaneous IL-2 injection in cancer patients. Tumori, 77:212–215, 1991.

    PubMed  CAS  Google Scholar 

  145. Lissoni, P., Barni, S., Tancini, G.: A randomized study with subcutaneous low-dose IL-2 alone vs. IL-2 plus the pineal hormone melatonin in advanced solid neoplasm other than renal cancer and melanoma. Br. J. Cancer, 69: 196–199, 1994.

    PubMed  CAS  Google Scholar 

  146. Lissoni, P., Meregalli, S., Fossati, V.: A randomized study of immunotherapy with low-dose subcutaneous IL-2 plus melatonin vs. chemotherapy with cisplatin and etoposide as first-line therapy for advanced non-small lung cancer. Tumori, 80:464–467, 1994.

    PubMed  CAS  Google Scholar 

  147. Barni, S., Lissoni, P., Cazzaniga, M.: Neuro-immunotherapy with subcutaneous low-dose IL-2 and the pineal hormone melatonin as a second-line treatment in metastatic colorectal carcinoma. Tumori, 78:383–387, 1992.

    PubMed  CAS  Google Scholar 

  148. Turek, F.W.: Melatonin hype hard to swallow. Nature, 379:295–296, 1996.

    Article  PubMed  CAS  Google Scholar 

  149. Cunningham, D.A., and Hill, J.S.: Effects of training on cardiovascular response to exercise. J. Appl. Physiol., 39:891–895, 1975.

    PubMed  CAS  Google Scholar 

  150. Mahan, M.P. and Young, R.M.: Immune parameters of untrained or exercise-trained rats after exhaustive exercise. J. Appl. Physiol., 66:282–287, 1989.

    PubMed  CAS  Google Scholar 

  151. Shu, J., Stevenson, J.R., and Zhou, Z.: Modulation of cellular immune responses by cold water stress in the rat. Develop. Comp. Immunol., 17:357–371, 1993.

    Article  CAS  Google Scholar 

  152. Ferry, A., Weill, B.L., and Rieu, A.M.: Immuno-modulations induced in rats by exercise on a treadmill. J. Appl. Physiol., 69:1912–1915, 1990.

    PubMed  CAS  Google Scholar 

  153. Fernandes, G, Rozek, M., and Troyer, D.: Reduction of blood pressure and restoration of T-cell immune function in spontaneously hypertensive rats by food restriction and/or by treadmill exercise. J. Hypertension, 4: S469–S474, 1986.

    CAS  Google Scholar 

  154. Tharp, G.D. and Preuss, T.L.: Mitogenic response of T lymphocytes to exercise training and stress. J. Appl. Physiol., 70:2535-25-38, 1991.

    Google Scholar 

  155. Simpson, J.R. and Hoffman-Goetz, L.: Exercise stress and murine natural killer cell function. Prec. Soc. Exp. Biol. Med., 195:129–135, 1990.

    CAS  Google Scholar 

  156. Ortega, E., Forner, M.A., Barriga, C., and De La Fuente, M.: Effect of age and of swimming-induced stress on the phagocytic capacity of peritoneal macrophages from mice. Mech. Ageing Dev., 70:53–63, 1993.

    Article  PubMed  CAS  Google Scholar 

  157. Filteau, S.M., Menzies, R.A., Kaido, T.J., O’Grady, M.P., Gelderd, J.B., and Hall, N.R.: Effects of exercise on immune functions of undernourished mice. Life Sci., 51:565–574, 1992.

    Article  PubMed  CAS  Google Scholar 

  158. De La Fuente, M., Fernandez, M.D., Miguel, J., and Hernanz, A.: Changes with aging and physical activity in ascorbic acid content and proliferative response of murine lymphocytes. Mech. Ageing Dev., 65:177–186, 1992.

    Article  PubMed  Google Scholar 

  159. Hoffman-Goetz, L., Keir, R., Thorne, R., Houston, M.E., and Young, C.: Chronicexercise stress in mice depresses splenic T lymphocyte mitogenesis in vitro. Clin. Exp. Immunol., 66:551–557, 1986.

    PubMed  CAS  Google Scholar 

  160. Conn, C.A., Rozak, W.E., Tooten, P.J., Gruys, E., Borer, K.T., and Kluger, M.J.: Effect of voluntary exercise and food restriction in response to lipopolysaccharide in hamsters. J. Appl. Physiol., 78:466–477, 1995.

    PubMed  CAS  Google Scholar 

  161. Tomasi, T.B., Thudeau, F.B., Czerwinski, D., and Erredge, S.: Immune parameters in athletes before and after strenuous exercise. J. Clin. Immunol., 2:173–177, 1982.

    Article  PubMed  CAS  Google Scholar 

  162. Crist, D.M., Mackinnon, L.T., Thompson, R.F., Atterbon, H.A., and Egan, P.A.: Physical exercise increases natural cellular-mediated tumor cytotoxicity in elderly women. Gerontol., 35:66–71, 1989.

    Article  CAS  Google Scholar 

  163. Papa, S., Vitale, M., Mazzotti, G., Neri, L., Monti, G., and Manzoli, F.: Impaired lymphocyte stimulation induced by long-term training. Immunol. Lett., 22:29–33, 1989.

    Article  PubMed  CAS  Google Scholar 

  164. MacNeil, B., Hoffman-Goetz, L., Kendall, A., Houston, M., and Arumagam, Y.: Lymphocyte proliferation responses after exercise in men: fitness, intensity, and duration. J. Appl. Physiol., 70:179–185, 1991.

    PubMed  CAS  Google Scholar 

  165. Eskola, J., Ruuskanen, E., Soppi, E.: Effect of sport stress on lymphocyte transformation and antibody production. Clin. Exp. Immunol., 32:339–345, 1978.

    PubMed  CAS  Google Scholar 

  166. Lewicki, R., Tchorzewski, H., Majewska, E., Nowak, Z., and Baj, Z.: Effect of maximal physical exercise on T lymphocyte subpopulations and on interleukin-1 (IL-1) and interleukin-2 (IL-2) production in vitro. Int. J. Sports Med., 9:114–117, 1988.

    PubMed  CAS  Google Scholar 

  167. Fiatarone, M.A., Morley, J.E., Bloom, E.T., Benton, D., Solomon, G.F., and Makinodan, T.: The effect of exercise on natural killer cell activity in young and old subjects. J. Gerontol., 44:M37–45, 1989.

    PubMed  CAS  Google Scholar 

  168. Ferry, A., Picard, F., Duvallet, A., Weill, B., and Rieu, M.: Changes in blood leukocyte populations induced by acute maximal and chronic submaximal exercise. Eur. J. Appl. Physiol., 59:435–442, 1990.

    Article  CAS  Google Scholar 

  169. Hanson, P.G., and Flaherty, D.K.: Immunological responses to training in conditioned runners. Clin. Sci., 60:225–228, 1981.

    PubMed  CAS  Google Scholar 

  170. Liu, Y.G., and Wang, S.Y.: The enhancing effect of exercise on production of antibody to Salmonella typhi in mice. Immunol. Lett., 14:117–120, 1987.

    Article  PubMed  CAS  Google Scholar 

  171. Peters, B.A., Sothmann, M., and Wehrenberg, W.B.: Blood leukocyte and spleen lymphocyte immune responses in chronically physically active and sedentary hamsters. Life Sci., 45:2238–2245, 1989.

    Article  Google Scholar 

  172. Hedfors, E., Holm, G., and Ohnel, B.: Variations of blood lymphocytes during work studied by cell surface markers, DNA synthesis, and cytotoxicity. Clin. Exp. Immunol., 24:328–335, 1976.

    PubMed  CAS  Google Scholar 

  173. Hoffman-Goetz, L., Keir, R., Thorne, R., Houston, M.E., and Young, C.: Chronicexercise stress in mice depresses splenic T lymphocyte mitogenesis in vitro. Clin. Exp. Immunol., 66:551–557, 1986.

    PubMed  CAS  Google Scholar 

  174. Oshida, Y., Yamanouchi, K., Hayamizu, U., and Sato, Y.: Effect of acute physical exercise on lymphocyte subpopulations in trained and untrained subjects. Int. J. Sports Med., 9:137–140, 1988.

    Article  PubMed  CAS  Google Scholar 

  175. Fitzgerald, L.: Exercise and immune system. Immunol. Today, 11:337–339, 1988.

    Article  Google Scholar 

  176. Khansari, D.N., Murgo, A.J., and Faith, R.E.: Effects of stress on immune system. Immunol. Today, 11: 170–175, 1990.

    Article  PubMed  CAS  Google Scholar 

  177. Hoffman-Goetz, L., Thorne, R.J., and Houston, M.E.: Splenic immune responses following treadmill exercise in mice. Can. J. Physiol. Pharmacol., 66:1405–1419, 1988.

    Google Scholar 

  178. Rail, L.C., Roubenoff, R., Cannon, J.G., Abad, L.W., Dinarello, C.A., and Meydani, S.N.: Effects of progressive resistance training on immune response in aging and chronic inflamation. Med. Sci. Sports Exerc. 28: 1356–1365, 1996.

    Google Scholar 

  179. Nieman, D.C., Henson, D.A., and Gusewitch, G.: Physical activity and immune function in eldely women. Med. Sci. Sports Exer., 25:823–831, 1993.

    CAS  Google Scholar 

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  1. Geriatric Research, Education and Clinical Center, South Texas Veterans Health Care System, University of Texas Health Science Center, San Antonio, Texas, 78284

    Mohammad A. Pahlavani Ph.D.

  2. Department of Physiology, University of Texas Health Science Center, San Antonio, Texas, 78284

    Mohammad A. Pahlavani Ph.D.

  3. GRECC (182), Audie Murphy VA Hospital, 7400 Merton Minter Blvd., San Antonio, TX, 78284

    Mohammad A. Pahlavani Ph.D.

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Pahlavani, M.A. Intervention in the aging immune system: Influence of dietary restriction, dehydroepiandrosterone, melatonin, and exercise. AGE 21, 153–173 (1998). https://doi.org/10.1007/s11357-998-0025-5

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