Abstract
The immune system plays an important role in protection against infection and in the maintenance of the internal environment of the body. However, such important immune functions are known to decline with age in many mammals, including humans. It is a matter of clinical importance that the incidence of various age-associated diseases such as infections, cancer and vascular disorders increases with a decrease in immunological vigor. The extent of immunologic decline is variable and exhibits wide inter-individual variations. Thus, it is important to assess the extent of immunologic decline in both patients suffering from various diseases and in healthy people in order to maintain healthy conditions. To this end, we have developed a scoring system that analyzes immune parameters according to a database of known age-associated immune changes obtained from a healthy population. Using this scoring system, we can combine several different immunological parameters and express the immune status of individuals as a simple numeral.
After determining immunological vigor for individuals, it is necessary to replenish immune defects and restore them to normalcy for individuals with depressed immunological scores. This chapter provides methods of immunological restoration in animal models and introduces some similar attempts in humans. The effect of any immunological restoration varies with the individual and must therefore verified. Currently, the proposed immune scoring system proposed is useful to determine whether the methods employed are effective for the restoration of immune functions.
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References
Abe S, Tansho S, Ishibashi H, Inagaki N, Komatsu Y, Yamaguchi H (1998) Protective effect of oral administration of a traditional medicine, Juzen-taiho-to, and its components on lethal Candida albicans infection in immunosuppressed mice. Immunopharm Immunot 20:421–431
Ames BN, Shigenaga MK, Hagen TM (1993) Oxidants, anti-oxidants, and the degenerative diseases of aging. Proc Natl Acad Sci 90:7915–7922
Asanuma H, Hirokawa K, Utsuyama M et al (2001) Immune responses and protection in different strain of aged mice immunized intranasally with an adjuvant-combined influenza virus. Vaccine 19:3981–3989
Berd D, Maguire HC, Mastrangelo MJ (1984) Potentiation of human cell-mediated and humoral immunity by low-dose cyclophosphamide. Cancer Res 44:5439–5443
Castle SC, Uyemura K, Fulop T, Hirokawa K, Makinodan T (2006) A need study the immune status of frail older adults. Immune Ageing doi: 10.1186/1742-4933-3-1
Chrousos GP, McCarty R, Pacak K, Cizza G, Sternberg E, Gold PW, Kvetnansky R (1995) Stress: Basic mechanism and clinical implications. Ann N Y Acad Sci 771:1–745
Clark R (1997) The somatogenic hormones and Insulin-like growth factor-1: stimulators of lymphopoiesis and immune function. Endocr Rev 18:157–179
Dunn GP, Bruce AT, Ikeda H, Old LJ, Schreiber RD (2002) Cancer Immunoediting: from immuno surveillance to tumor escape. Nat Immunol 3:991–998
Ershler WB, Longo DL (1997) Aging and cancer: issues of basic and clinical science. J Natl Cancer Inst 89:1489–1497
Everitt AV, Le Couteur DG (2007) Life extension by caloric restriction in humans. Ann N Y Acad Sci 1114:423–433
Fahlman MM, Boardley D, Flynn MG et al (2000) Effects of hormone replacement therapy on selected indices of immune function in postmenopausal women. Gynecol Obstet Invest 50:189–193
Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 1:298–300
Heilbronn LK, Ravussin E (2003) Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr 78:361–369
Hirokawa K, Utsuyama M, Ishikawa T, Kikuchi Y, Kitagawa M, Fijii Y, Nariuchi H, Uetake H and Sugihara Decline of T cell related immune functions in cancer patients and a trial of immunological restoration by infusion of activated autologous T cells. Mech Ageing Dev 2008 May 8 (Epub ahead of print)
Hirokawa K, Utsuyama M, Kikuchi Y and Kitagawa M. Scoring of immunological vigor: trial assessment of immunological status as a whole for elderly people and cancer patients. In Immunosenescnece (Pawelec G ed) pp 15–31, 2008, Landes Bioscience
Hirokawa K (1992) Understanding the mechanism of the age-related decline in immune function. Nutr Rev 50:361–366
Hirokawa K, Utsuyama M, Kikuchi Y, Kitagawa M (2007) Proper assessment and restoration of immunological function for the improvement of QOL and elongation of healthy lifespan in the elderly. In: Sinigoji Hirokawa, Jones & Linhart (eds) Impact of ageing. A common challenge for Europe and Asia
Hirokawa K, Utsuyama M, Kikuchi Y (2007) Scoring of immunological vigor; trial assessment of immunological status as a whole for the elderly people and cancer patients. In: Pawelec G (ed) Immunosenescence Landes Bioscience
Hirokawa K, Utsuyama M (2002) Animal models and possible human application of immunological restoration in the elderly. Mech Ageing Dev. 123:1055–1063
Hirokawa K, Utsuyama M, Makinodan K (2006) Immunity and aging. In: Pathy MSJ, Sinclair AJ, Morley JE (eds) Principles and practice of geriatric medicine. 4th Edition pp 19–36
Hirokawa K, Utsuyama M, Kobayashi S (2001) Hypothalamic control of thymic function. Cell Mol Biol (Noisy-le-grand) 47:97–102
Hirokawa K, Utsuyama M, Kobayashi S (1998) Hypothalamic control of development and aging of the thymus. Mech Ageing Dev 100:177–185
Hirokawa K, Utsuyama M (1984) The effect of sequential multiple grafting of syngeneic newborn thymus on the immune functions and life expectancy of aging mice. Mech Ageing Dev 28:111–121
Hirokawa K, Utsuyama M (1989) Combined grafting of bone marrow and thymus, and sequential multiple thymus grafting in various strains of mice. The effect on immune functions and life span. Mech Ageing Dev 49:49–60
Hirokawa K (2003) Aging and immunity. Jpn J Geriatr 40:543–552
Ichikawa M, Fujita Y, Ebisawa H, Ozeki T (2000) Effects of long-term, light exercise under restricted feeding on age-related changes in physiological and metabolic variables in male Wistar rats. Mech Ageing Dev 113:23–35
Ishiyama N, Utsuyama M, Hirokawa et al (1999) Immunological enhancement with a low dose of cyclophosphamide in aged mice. Mech Ageing Dev 111:1–12
Kaneko M, Kawakita T, Kumazawa Y, Takimoto H, Nomoto K, Yoshizawa T (1999) Accelerated recovery from cyclophosphamide-induced leukopenia in mice administered a Japanese ethical herbal drug, Hochu-ekki-to. Immunopharmacol 44:223–231
Khorram O, Yeung M, Vu L, Yen SS (1997) Effects of [norleucine27] growth hormone-releasing hormone (GHRH) (1-29)-NH2 administration on the immune system of aging men and women. J Clin Endocrinol Metab 82:3590–3596
Koo GC, Huang C, Camacho R, Trainor C, Blake JT, Sirotina-Meisher A, Schleim KD, Wu TJ, Cheng K, Nargund R, McKissick G (2001) Immune enhancing effect of a growth hormone serectagogue. J Immunol 166:4195–4201
Linton PJ, Dorshkind K (2004) Age-related changes in lymphocytes development and function. Nat Immunol 5:3974–3984
Mac Gee W (1993) Cause of death in a hospitalized geriatric population: an autopsy study of 3000 autopsy patients. Virchows Arch A 423:343–349
MaCay CM, Crowell MF, Maynard LA (1935) The effect of retarded growth upon the length of life span and upon ultimate body size. J Nutr 10:63–79
Makinodan T, Kay MMB (1980) Age influence on the immune system. Adv Immunol 29:287–330
Marko MG, Ahmed T, Bunnell SC et al (2007) Age-associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation. J Immunol 178:1443–1449
Martin GM, Austad SN, Johnson TE (1996) Genetic analysis of ageing: role of oxidative damage and environmental stresses. Nat Genet 13:25–34
Meydani SN, Lipman RD, Han SN et al (1998) The effect of long-term dietary supplementation with anti-oxidants. Ann N Y Acad Sci 854:352–360
Messaoudi I, Warner J, Fischer M et al (2006) Delay of T cell senescence by caloric restriction in aged long-lived non-human primates. Proc Natl Acad Sci U S A 103:19448–19453
Mori K, Kido T, Daikuhara H, Sakakibara I, Sakata T, Shimizu K, Amagaya T, Sasaki H, Komatsu Y (1999) Effect of Hochu-ekki-to (TJ-41), a Japanese herbal medicine, on the mice infected with influenza virus. Antiviral Res 15:103–111
Morio T (2001) Adoptive immunotherapy by activated T cells. Tokyo pediatrician conference report 20:22–25 (In Japanese)
Onishi Y, Fujii H, Hayakawa Y, Sakukawa R, Yamaura T, Sakamoto T, Tsukada K, Fujimaki M, Nunome S, Komatsu Y, Saiki I (1998) Oral administration of a Kampo (Japanese herbal) medicine Juzen-Taiho-To inhibits liver metastasis of colon 26-15 carcinoma cells. Jpn J Cancer Res 89:206–213
Park OJ, Kim HY, Kim WK et al (2003) Effect of vitamin E supplementation on antioxidant defense systems and humoral immune responses in young, middle-aged and elderly Korean women. J Nutr Sci Vitaminol 49:94–99
Pawelec G, Akbar A, Caruso C et al (2004) Is immunosenescence infectious? Trends Immunol 25:406–410
Peryy JK, Emerald BS, Mertani HC, Lobie PE (2006) The oncogenic potential of growth hormone. Growth Horm IGF Res 16;277–289
Price GB, Makinodan T (1972) Immunologic deficiencies in senescence. I. Characterization of intrinsic deficiencies. J Immunol 108:403–412
Price GB, Makinodan T (1972) Immunologic deficiencies in senescence. II. Characterization of extrinsic deficiencies. J Immunol 108:413–417
Roberts-Thomson IC, Whittingham S, Youngchaiyud U, Mackay IR (1974) Ageing, immune response and mortality. Lancet 2(7877):368–370
Rosenberg SA (2001) Progress in human tumour immunology and immunotherapy. Nature 411:380–384
Roth GS, Lane MA, Ingram DK et al (2002) Biomarkers of caloric restriction may predict longevity in human. Science 297:811-
Sutherland JS, Goldberg GL, Hammett MV, Uldrich AP, Berzins SP, Heng TS, Blazar BR, Millar JL, Malin MA, Chidgey AP, Boyd RL (2005) Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol 175(4):2741–2753
Saiki I, Yamaura T, Ohnishi Y, Hayakawa Y, Komatsu Y, Nunome S (1999) HPLC analysis of juzen-taiho-to and its variant formulations and their anti-metastatic efficacies. Chem Pharm Bull 47:1170–1174
Stopinska-Gluszak U, Waligora J, Grzela T et al (2006) Effect of estrogen/progesterone hormone replacement therapy on natural killer cell cytotoxicity and immunoregulatory cytokine release by peripheral blood mononuclear cells of postmenopausal women. J Reprod Immunol 69:65–75
Sutherland JS, Glodberg GL, Hammett MV, et al (2005) Activation of thymic regeneration in mice and humans following androgen blockade. J Immunol 175:2741–2753
Tsunemi A, Utsuyama M, Seidler BKH, Kobayashi S, Hirokawa K (2005) Age-related decline of brain monoamines in mice is reversed to young level by Japanese herbal medicine. Neurochem Res 30:75–81
Utsuyama M, Hirokawa K (1989) Hypertrophy of the thymus and restoration of immune functions in mice and rats by gonadectomy. Mech Ageing Dev 47(3):175–185
Utsuyama M, Ichikawa M, Konno-Shirakawa A, Fujita Y, Hirokawa K (1996) Retardation of the age-associated decline of immune functions in aging rats under dietary restriction and daily physical exercise. Mech Ageing Dev 91:219–228
Utsuyama M, Seidler H, Kitagawa M, Hirokawa K (2001) Immunological restoration and antitumor effect by Japanese herbal medicine in aged mice. Mech Ageing Dev 122:341–335
Utsuyama M, Hirokawa K (1989) Hypertrophy of the thymus and restoration of immune functions in mice and rats by gonadectomy. Mech Ageing Dev 47:175–185
Utsuyama M, Shiraishi J, Takahashi H, Kasai M, Hirokawa K (2003) Glia maturation factor produced by thymic epithelial cells plays a role in T cells differentiation in thymic microenvironment. Int Immunol 15:557–564
Yamaguchi T, Bamba K, Kitayama A, Kuroiwa Y, Yoshimatsu K, Shimakawa T, Ogawa K, Sekine T, Shimizu N, Yamamoto K (2004) Long-term intravenous administration of activated autologous lymphocytes for cancer patients does not induce anti-nuclear antibody and rheumatoid factor. Anticancer Res 24:2423–2429
Wachi M, Koyama M, Utsuyama M, Bittman BB, Kitagawa M, Hirokawa K (2007) Recreational music-making modulates natural killer cell activity, cytokines, and mood states in corporate employees. Med Sci Monit 13:57–70
Wakikawa A, Utsuyama M, Wakabayashi A, Kitagawa M, Hirokawa K (1999) Vitamin E enhances the immune functions of young, but not old mice under restraint stress. Exp Gerontol 34:853–862
Zuniga-Pfucker JC (2004) T-cell development made simple. Nat Rev Immunol 4:67–72
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Hirokawa, K., Utsuyama, M., Kikuchi, Y., Kitagawa, M. (2009). Assessment of Age-related Decline of Immunological Function and Possible Methods for Immunological Restoration in Elderly. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_73
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