Hostname: page-component-cd9895bd7-gbm5v Total loading time: 0 Render date: 2024-12-26T08:51:45.015Z Has data issue: false hasContentIssue false
  • English
  • Français

Immune response during disease and recovery in the elderly

Published online by Cambridge University Press:  08 December 2008

Bruno Lesourd
Bruno Lesourd*
Affiliation:
Unité de Médecine Nutritionnelle Gériatrique, Hôpital Charles Foix, 7 Avenue de la République, 94200 Ivry sur seine, France
*
Corresponding author: Dr Bruno M. Lesourd, fax +33 1 49 59 45 27, email bruno.lesourd@cfx.ap-hop-paris.fr
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.

The present article reviews immune ageing and its relationship with nutritional ageing, with a particular insight into the influences of disease on both ageing processes. Immune ageing can be described primarily as the progressive appearance of immune dysregulations, mainly acquired immunity (mature: immature, naive: memory T lymphocyte subset decreases) leading to gradual increases in T-helper 2: T-helper 1 cells. This change is due initially to decreased thymic function, and later to accumulative antigen pressure over the lifespan. In contrast, innate immunity (macrophage functions) is preserved during the ageing process and in the elderly this leads to macrophage–lymphocyte dysequilibrium, which is particularly critical during on-going disease. Indeed, any disease induces long-lasting acute-phase reactions in aged patients and leads to body nutritional reserve (mainly protein) losses. Episodes of disease in the aged patient progressively deplete body nutritional reserves and lead to protein–energy malnutrition, undernutrition-associated immunodeficiency, and finally cachexia. Undernutrition is a common symptom in the elderly; protein-energy malnutrition is found in more than 50 % of hospitalized elderly patients and in most elderly diseased subjects. In addition, micronutrient deficit or low levels are common in home-living self-sufficient apparently-healthy elderly subjects. All these nutritional deficits induce decreased immune responses, and micronutrient deficits are now thought to be partly responsible for the decreased immune responses (immune ageing?) observed in the apparently-healthy elderly. Indeed, several studies have shown that micronutrient supplements induce increased immune responses in the healthy elderly. The progression of infectious diseases depends on immune responses and on nutritional status before the onset of illness in aged subjects. In addition, recovery depends on the intensity of acute-phase responses in the undernourished elderly. In fact, chronic acute-phase responses, commonly associated with diseases in aged patients, lead to progressive lowering of metabolic responses in the undernourished elderly. This can be quantified by increased production of free radicals during treatment and these increases may explain the difficulty in successfully treating aged patients. Nutritive therapy in order to improve metabolic processes and also to maintain body reserves should be considered as a necessary adjuvant therapy in the treatment of elderly patients.

Keywords

Immune responseDiseaseAgeingElderly
Type
Reproduction and Development Group Symposium on ‘Nutrition and immunology from fetal life to old age’
Information
Proceedings of the Nutrition Society , Volume 58 , Issue 1 , February 1999 , pp. 85 - 98
Copyright
Copyright © The Nutrition Society 1999

References

Abo, T (1992) Extrathymic differentiation of T lymphocytes and its biological function. Biology in Medical Research 13, 1–39.Google Scholar
Adler, WH, Baskar, PV, Chrest, FJ, Dorsey-Cooper, B, Winchurch, RA & Nagel, JE (1997) HIV infection and ageing: mechanisms to explain the accelerated rate of progression in the older patient. Mechanism of Ageing and Development 96, 137–155.Google Scholar
Alès-Martinez, JE, Alvarez-Mon, M, Merino, F, Boniilla, F, Martinez-Alés, C, Durantez, A & De La Hera, A (1988) Decreased TcR-CD3- T cell numbers in healthy aged humans. Evidence that T cell defects are masked by a reciprocal increase of TcR-CD3- CD2+ natural killer cells. European Journal of Immunology 18, 1827–1830.CrossRefGoogle Scholar
Allard, JP, Aghdassi, E, Chau, J, Salit, I & Walmsley, S (1998) Oxidative stress and plasma antioxidant micronutrients in humans with HIV infection. American Journal of Clinical Nutrition 67, 143–147.Google Scholar
Arreaza, EE, Gibbons, JJ, Sisking, GW & Weksler, ME (1993) Lower antibody response to tetanus toxoid associated with higher auto-anti-idiotype antibody in old compared with young humans. Clinical Experimental Immunology 92, 169–176.CrossRefGoogle Scholar
Barrat, F, Lesourd, BM, Louise, A, Boulouis, HJ, Vincent-Naulleau, S, Thibault, D, Neway, T, Sanaa, M & Pilet, Ch (1997) Surface antigens expression in spleen cells of C57 BL/6 mice during aging: influence of sex and breeding. Clinical Experimental Immunology 107, 593–600.Google Scholar
Batory, G, Janeso, A, Puskas, E, Redei, A & Lengyei, E (1984) Antibody and immunoglobulin levels in aged humans. Archives of Gerontology and Geriatrics 3, 175–188.Google Scholar
Baumann, C, Badamchiam, M & Goldstein, AL (1995) Thymosin a1 antagonizes induced apoptosis of developing thymocytes in vitro. Molecular Cell Biology 6, 356a.Google Scholar
Beharka, AA, Wu, D, Han, SN & Meydani, SN (1997) Macrophage prostaglandin production contributes to the age-associated decrease in T cell function which is reversed by the dietary antioxidant vitamin E. Mechanism of Ageing and Development 96, 203–208.Google Scholar
Bendich, A (1990) Antioxidant micronutrient and immune responses. Annals of the New York Academy of Sciences 587, 168–180.CrossRefGoogle ScholarPubMed
Bogden, JD, Bendich, A, Kemp, FW, Bruening, KS, Shurrick, JH, Denny, T, Baker, H & Louria, DB (1994) Daily micronutrient supplements enhance delayed-hypersensitivity skin test responses in older people. American Journal of Clinical Nutrition 60, 437–447.CrossRefGoogle ScholarPubMed
Bogden, JD, Oleske, JM, Lavenhar, MA, Munves, EM, Kemp, FW, Bruening, KS, Holding, KJ, Denny, TN, Guarino, MA & Holland, BK (1990) Effects of one year of supplementation with zinc and other micronutrients on cellular immunity in the elderly. Journal of the American College of Nutrition 9, 214–225.CrossRefGoogle ScholarPubMed
Bogden, JD, Oleske, JM, Munves, EM, Lavenhar, MA, Bruening, KS, Kemp, FW, Holding, KJ, Denny, TN & Louria, DB (1987) Zinc and immunocompetence in the elderly: baseline data on zinc nutriture and immunity in unsupplemented subjects. American Journal of Clinical Nutrition 45, 101–109.CrossRefGoogle Scholar
Boukaïba, N, Flament, C, Acher, S, Chappuis, Ph, Pian, A, Fusselier, M, Dardenne, M & Lemonnier, D (1993) A physiological amount of zinc supplementation: effects on nutritional, lipid, and thymic status in an elderly population. American Journal of Clinical Nutrition 57, 566–572.Google Scholar
Brohee, D (1987) Age et sous-populations lymphocytaires: analyse critique de la litterature (Ageing and lymphocyte subsets: critical analysis of the literature). Revue de Gériatrie 12, 199–203.Google Scholar
Cakman, I, Rohwer, J, Schûtz, RM, Kirchner, H & Rink, L (1996) Dysregulation between TH1 and TH2 cell sub-populations in the elderly. Mechanism of Ageing and Development 87, 197–209.CrossRefGoogle Scholar
Carlson, GL & Little, RA (1992) The pathophysiology and pattern of the hormonal response to severe sepsis. In Conséquences Endocriniennes des États d'Agression Aigue: Collection Perspectives en Réanimation (Endocrine Consequences of Acute States: an Overview), pp. 57–68 [Bowles, JM, editor]. Paris: Arnette.Google Scholar
Castle, S, Uyemura, K, Wong, W, Modlin, R & Effros, R (1997) Evidence of enhanced type 2 immune response and impaired upregulation of a type 1 response in frail elderly nursing home residents. Mechanism of Ageing and Development 94, 7–16.Google Scholar
Cederholm, T, Wretlind, B, Hellstrom, K, Andersson, B, Engstrom, L, Brismar, K, Scheynius, A, Forslid, J & Palmblad, J (1997) Enhanced generation of interleukins 1β and 6 may contribute to the cachexia of chronic disease. American Journal of Clinical Nutrition 65, 876–882.CrossRefGoogle Scholar
Chandra, RK (1972) Immunocompetence in undernutrition. Journal of Pediatrics 81, 1194–1200.Google ScholarPubMed
Chandra, RK (1983) Numerical and functional deficiency in T helper cells in protein energy malnutrition. Clinical Experimental Immunology 51, 126–132.Google Scholar
Chandra, RK (1988) Nutrition, immunity and outcome; past, present and future. 11th Gopalan Gold Medal Oration. Nutrition Research 8, 225–237.Google Scholar
Chandra, RK (1992) Effect of vitamin and trace-element supplementation on immune responses and infection in elderly subjects. Lancet 340, 1124–1127.Google Scholar
Chandra, RK (1994) Nutritional regulation of immune function at the extremes of life: in infants and in the elderly. In Malnutrition Determinants and Consequences pp. 245–251 [White, P, editor]. New York: Alan R. Liss.Google Scholar
Chandra, RK, Chandra, S & Gupta, S (1984) Antibody affinity and immune complexes after immunization with tetanus toxoid in protein-energy malnutrition. American Journal of Clinical Nutrition 40, 131–134.Google Scholar
Chen, WF, Liu, SL, Gao, XM & Pang, XI (1987) The capacity of lymphokine production by peripheral blood lymphocytes from aged humans. Immunology Investigation 15, 575–583.Google Scholar
Clerici, M & Shearer, GM (1994) The Th1/Th2 hypothesis of HIV infection: new insights. Immunology Today 15, 575–581.CrossRefGoogle ScholarPubMed
Commissariat Général du Plan (1993) Santé 2010 - Groupe Prospective du Système de Santé (Health 2010; A Report from the Public Health System Prospective Group). Paris: La Documentation Française.Google Scholar
Cossarizza, A, Ortolani, C, Forti, E, Montagnani, G, Paganelli, R, Zanotti, M, Marini, M, Monti, D & Franceschi, C (1991) Age-related expansion of functionally inefficient cells with markers of natural killer activity in Down's syndrome. Blood 77, 1263–1270.Google Scholar
Cossarizza, A, Ortolani, C, Paganelli, R, Monti, D, Barbieri, D, Sansoni, P, Fagiolo, U, Forti, E, Londei, M & Franceschi, C (1992) Age-related imbalance of virgin (CD45RA+) and memory (CD45RO+) cells between CD4+ and CD8+ T lymphocytes in humans: study from newborns to centenarians. Journal of Immunology Research 4, 117–126.Google Scholar
Crawford, J, Eye, MK & Cohen, HJ (1987) Evaluation of monoclonal gammopathies in the well elderly. American Journal of Medicine 82, 39–45.Google Scholar
Curtis, GE, McAtear, CA, Formela, L, Walsh, A & Shenkin, A (1995) The effect of nutritional status on the cytokine and acute phase protein responses to elective surgery. Cytokine 7, 380–388.Google Scholar
De la Fuente, M & Munoz, ML (1992) Impairment of phagocytic process in macrophages from young and old mice by protein malnutrition. Annals of Nutrition and Metabolism 36, 41–47.CrossRefGoogle Scholar
Deviere, J, Kennes, B, Giosset, J, De Maertelaer, V & Neve, P (1985) Immune senescence: effect of age, sex and health on human blood mononuclear subpopulations. Archives of Gerontology and Geriatrics 4, 285–293.CrossRefGoogle ScholarPubMed
Dutta, C & Hadley, EC (1995) The significance of sarcopenia in old age. Journal of Gerontology 50, 1–4.Google Scholar
Ershler, WB, Sun, WH, Binkley, N, Gravenstein, S, Volk, MJ, Kamoske, G, Kloop, RG, Roecker, EB, Daynes, RA & Weindruch, R (1993) Interleukin-6 and aging: blood levels and mononuclear cell production increase with advancing age and in vitro production modifiable by dietary restriction. Lymphokine and Cytokine Research 12, 225–230.Google Scholar
Feldman, EB (1993) Aspects of the interrelations of nutrition and aging: perspective. American Journal of Clinical Nutrition 58, 1–3.Google Scholar
Fereday, A, Gibson, NR, Cox, M, Pacy, PJ & Millward, DJ (1997) Protein requirements and ageing: metabolic demand and efficiency of utilization. British Journal of Nutrition 77, 685–702.Google Scholar
Fernandes, G, Venkatraman, JT, Turturro, A, Attwood, VG & Hart, RW (1997) Effect of food restriction on lifespan and immune functions in long-lived Fischer-344 × Brown Normay F1 Rats. Journal of Clinical Immunology 17, 85–95.Google Scholar
Filteau, SM & Hall, NRS (1991) Increased production of tumor necrosis factor and interleukin 1 by peritoneal macrophages from severely undernourished mice: lack of correlation with serum corticosterone. Nutrition Research 11, 1001–1011.Google Scholar
Frasca, D & Doria, G (1997) Recombinant cytokines as an approach to immune reconstitution in aging. Developmental and Comparative Immunology 21, 525–530.CrossRefGoogle ScholarPubMed
Galan, P, Preziosi, P, Richard, MJ, Monget, AL, Arnaud, J, Lesourd, B, Favier, A, Girodon, F, Laisney, C, Bourgeois, CF, Keller, H, Hercberg, S & Le Réseau Gériatrie/MIN.VIT.AOX (1994) Biological and immunological effects of trace element and/or vitamin supplementation in the elderly. Proceedings of the 4th International Conference on Trace Elements in Medicine and Biology, pp. 197–210.Google Scholar
Girodon, F, Blache, D, Monget, AL, Lombart, M, Brunet-Lecompte, P, Arnaud, J, Richard, MJ & Galan, P (1997 a) Effect of a two-year supplementation with low doses of antioxidant vitamins and/or minerals in elderly subjects on levels of nutrients and antioxidant defense parameters. Journal of the American College of Nutrition 4, 357–365.Google Scholar
Girodon, F, Lombard, M, Galan, P, Brunet-Lecomte, P, Monget, AL, Arnaud, J, Preziosi, P & Hercberg, S (1997 b) Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Annals of Nutrition and Metabolism 41, 98–107.CrossRefGoogle ScholarPubMed
Goidl, EA, Chov, JW, Gibbons, JJ, Wekler, ME, Thorbecke, GJ & Siskind, GW (1983) Production of auto anti-idiotypic antibody during the normal auto-anti-idiotype antibody production by aged mice. Journal of Experimental Medicine 57, 635–645.Google Scholar
Goldberg, TH, Baker, DG & Shumacher, HR (1991) Interleukin-1 and the immunology of aging and disease. Aging, Immunology and Infectious Diseases 3, 81–86.Google Scholar
Goodwin, JS, Searles, RP & Tung, KSK (1982) Immunological responses of a healthy population. Clinical Experimental Immunology 48, 403–410.Google Scholar
Grigolo, B, Borzi, RM, Mariani, E, Monaco, CM, Cattini, L, Porstmann, T & Facchini, A (1994) Intracellular Cu/Zn superoxide dismutase levels in T and non-T cells from normal aged subjects. Mechanism of Ageing and Development 73, 27–37.Google Scholar
Gueldner, SH, Poon, LW, La Via, M, Virella, G, Michel, Y, Bramlett, MH, Noble, CA & Paulling, E (1997) Long term exercise patterns and immune function in healthy older women: a report of preliminary findings. Mechanism of Ageing and Development 96, 215–222.Google Scholar
Gupta, S (1986) Study of activated T cells in man. II. Interleukin 2 receptor and transferrin receptor expression on T cells and production of interleukin 2 in patients with the acquired immune deficiency syndrome (AIDS) and AIDS-related complex. Clinical Immunology and Immunopathology 38, 93–100.Google Scholar
Haller, J, Weggemans, RM, Lammi-Keefe, CJ & Ferry, M (1996) Changes in the vitamin status of elderly Europeans: plasma vitamins A, E, B-6, B-12, folic acid and carotenoids. European Journal of Clinical Nutrition 50, Suppl. 2, S32–S46.Google Scholar
Hallgren, HM, Bergh, N, Rodysill, KJ & O'Leary, JJ (1988) Lymphocyte proliferation responses to PHA and Anti CD3/Ti monoclonal antibodies, T cells surface marker expression and serum IL2 receptor levels as biomarkers of age and health. Mechanism of Ageing and Development 43, 175–185.Google Scholar
Harman, D (1995) Role of antioxidant nutrients in aging: overview. Age 18, 51–62.CrossRefGoogle Scholar
Haut Comité de la Santé Publique (1994) La Santé en France. Rapport Général (Health Status in France. A General Report). La Documentation Française, November.Google Scholar
Hayek, GM, Mura, C, Wu, D, Beharka, AA, Han, SN, Paulson, E, Hwang, D & Meydani, SN (1997) Enhanced expression of inducible cyclooxygenase with age in murine macrophages. Journal 159, 2445–2451.Google ScholarPubMed
Herndon, FJ, Hsu, HC & Mountz, JD (1997) Increased apoptosis of CD45RO− T cells with ageing. Mechanism of Ageing and Development 94, 123–134.CrossRefGoogle Scholar
Hijmans, W, Radl, J, Bottazo, GF & Doniach, D (1984) Autoantibodies in highly aged humans. Mechanism of Ageing and Development 26, 33–39.Google Scholar
Hirokawa, K, Utsuyama, M, Kasai, M, Kurishima, C, Ishijima, S & Zeng, YX (1994) Understanding the mechanisms of the age changes of thymic function to promote T cell differentiation. Immunology Letters 40, 269–277.Google Scholar
Hobbs, MV & Ernst, DN (1997) T cell differentiation and cytokine expression in late life. Developmental and Comparative Immunology 21, 464–470.Google Scholar
Institut National de la Statistique et des Etudes Epidémiologiques (1995) Projection de Population Totale pour la Franc Métropolitaine 1990 (Perspective Projection for the French Population in 1990). INSEE Publication no. 412, pp.22–25. Paris: INSEE.Google Scholar
Jennings, G, Bourgeois, C & Elia, M (1992) The magnitude of the acute phase protein response is attenuated by protein deficiency in rats. Journal of Nutrition 122, 1325–1351.Google Scholar
Johnson, LE (1990) Vitamin disorders in the elderly. In Geriatric Nutrition, 1st ed., pp.117–147 [Morley, JE, Glick, Z and Rubinstein, LZ, editors]. New York: Raven Press.Google Scholar
Jurivich, DA, Qiu, L & Welk, JF (1997) Attenuated stress responses in young and old human lymphocytes. Mechanism of Ageing and Development 94, 23–249.Google Scholar
Kehrer, JP & Smith, CB (1994) Free radicals in biology: sources, reactivities and roles in the etiology of human diseases In Natural Antioxidants in Human Health and Diseases, pp. 25–62. New York: Academic Press.Google Scholar
Khaled, MA, Kabir, I & Mahalanabis, D (1995) Effect of protein energy supplementation on oxidative stress in malnourished children. Nutrition Research 15, 1099–1104.Google Scholar
Klasing, KC (1988) Nutritional aspects of leukocyte cytokines: critical review. Journal of Nutrition 11, 1436–1446.Google Scholar
Kubo, M & Cinader, B (1990) Polymorphism of age-related changes in interleukin (IL) production: differential changes of T helper subpopulation, synthesizing IL-2, IL-3, and IL-4. European Journal of Immunology 24, 133–136.Google Scholar
Lang, GA, Naryshkin, S, Schneider, DL, Mills, BJ & Lindeman, RD (1992) Low blood glutathione levels in healthy aging adults. Journal of Laboratory and Clinical Medicine 120, 720–725.Google Scholar
Le, PH, Macker, HT & Cook, JE (1995) In situ detection and characterization of apoptotic thymocytes in human thymus. Journal of Immunology 154, 4371–4378.Google Scholar
Lee, J, Jiang, B, Inserra, P, Zhang, Z, Solkoff, D & Watson, RR (1998) Antioxidant supplementation in prevention and treatment of immune dysfunction and oxidation induced by murine AIDS in old mice. Nutrition Research 18, 327–339.Google Scholar
Lesourd, B (1990 a) Le vieillissement immunologique: influence de la dénutrition (Immune ageing: the effect of malnutrition). Annales de Biologie Clinique 48, 309–318.Google Scholar
Lesourd, B (1990 b) La dénutrition protéique: principale cause de déficit immunitaire chez le sujet âgé (Protein-energy malnutrition: the main cause of immunodeficiency in the elderly). Age and Nutrition 1, 132–138.Google Scholar
Lesourd, B (1992) Conséquences nutritionnelles des cytokines: facteur de gravité des hypercatabolismes chez le sujet âé (Nutritional consequences of cytokine secretion: a prognosis factor of hypercatabolism in elderly). Age and Nutrition 3, 100–109.Google Scholar
Lesourd, B (1993) Nutrition, immunité et vieillissement chez l'homme. Interférences nutritionnelles sur le vieillissement immunitaire humain normal et pathologique (Nutrition, immunity and ageing in human beings. Nutritional influences on immune ageing in healthy and diseased elderly). PhD Thesis. Université Paris VI.Google Scholar
Lesourd, BM (1994) La malnutrition protéino-énergétique chez les sujets âgés (Protein-energy malnutrition in aged persons). Semaines des Hôpitaux de Paris 70, 957–963.Google Scholar
Lesourd, BM (1995) Protein undernutrition as the major cause of decreased immune function in the elderly: clinical and functional implications. Nutrition Reviews 53, S86–S94.Google Scholar
Lesourd, BM (1996) Hypermetabolism: a frightening symptom that pushes elderly to enter a vicious circle. In Vitality Mortality and Ageing, Ageing Series no. 5, pp.363–376 [Viidik, A and Hofecker, G, editor]. Vienna: Facultas Universitäts Verlag Wien.Google Scholar
Lesourd, B, Congy, F, Nafziger, J, Salvatore, R, Deslandes, D & Moulias, R (1987) L'imuthiol en gériatrie. Influences sur la réponse à la vaccination grippale et sur les infections sévères lymphopéniantes (Imuthiol therapy in geriatrics. Influences on flu vaccine responses and on acute lymphopenic infections). Proceedings des Journées de l'Hôpital Claude Bernard. In Immunomodulateurs et Thérapeutique Anti-Infectieuse (Immunodulators and Anti-infection Therapy), pp. 47–51 [Pocidalo, JJ, Coulaud, JP, Vachon, F and Vilde, JL, editors]. Arnette.Google Scholar
Lesourd, B, Laisney, C, Salvatore, R, Meaume, S & Moulias, R (1994) Decreased maturation of T cell population factors on the appearance of double negative CD4-, CD8-, CD2+ cells. Archives of Gerontology and Geriatrics 4, Suppl., 139–154.Google Scholar
Lesourd, BM & Mazari, L (1997) Immune responses during recovery from protein-energy malnutrition. Clinical Nutrition 16, Suppl. 1, 37–46.Google Scholar
Lesourd, BM, Mazari, L & Ferry, M (1998) The role of nutrition in immunity in the aged. Nutrition Reviews 56, S113–S125.Google Scholar
Lesourd, B & Meaume, S (1994) Cell-mediated immunity changes in aging: relative importance of cell subpopulation switches and of nutritional factors. Immunology Letters 40, 235–242.CrossRefGoogle ScholarPubMed
Lesourd, BM, Moulias, R, Favre-Berrone, M & Rapin, CH (1992) Nutritional influences on immune responses in elderly. In Nutrition and Immunology, pp. 211–223 [Chandra, RK, editor]. St John's, Canada: ARTS Biomedical.Google Scholar
Lewis, VM, Twomey, JJ, Bealmer, P, Goldstein, G & Good, RA (1978) Age, thymic involution and circulating thymic hormone activity. Journal of Clinical Endocrinology and Metabolism 47, 145–150.Google Scholar
Ligthart, GJ, Corberand, JX, Fournier, C, Galanaud, P, Hijmans, W, Kennes, B, Muller-Hermelink, HK & Steinmann, GG (1984) Admission criteria for immunogerontological studies in man: the Senieur protocol. Mechanism of Ageing and Development 28, 47–55.Google Scholar
Ligthart, GJ, Radl, J, Corberand, JX, Van NieuwKoop, JAV, Van Stanalduinen, GJ, Ducos, J, Van Helmond, W & Hijmans, W (1990) Monoclonal gammopathies in human aging: increased occurrence with age and correlation with health status. Mechanism of Ageing and Development 52, 235–243.Google Scholar
Ligthart, GJ, Van Vlokhoven, PC, Schuit, HRE & Hijmans, W (1986) The expanded null cell compartment in ageing: increase in the number of natural killer cells and changes in T-cell and NK-cells subset in human blood. Immunology 59, 353–357.Google Scholar
Lucey, DR, Clerici, M & Shearer, GM (1996) Type 1 and type 2 cytokine dysregulation in human infectious, neoplastic and inflammatory diseases. Clinical Microbiological Reviews 9, 532–562.Google Scholar
McBean, AM, Babish, JD, Warren, JL & Melson, EA (1993) The effects of influenza epidemics on the hospitalization of persons 65 years and older. In Options for the Control of Influenza, vol. 2, pp.25–36 [Hannoun, C, editor]. Amsterdam: Elsevier.Google Scholar
McConkney, DJ, Hartzell, P, Chow, SC, Orrenius, S & Jondal, M (1990) Interleukin 1 inhibits T cell receptor-mediated apoptosis of immature thymocytes. Journal of Biological Chemistry 265, 3009–3011.Google Scholar
McMurray, DN (1998) Impact of nutritional deficiencies on resistance to experimental pulmonary tuberculosis. Nutrition Reviews 56, S147–S152.Google Scholar
Mackall, CL & Gress, RE (1997) Thymic aging and T-cell regeneration. Immunological Reviews 160, 91–102.Google Scholar
Makinodan, T & Kay, MMB (1980) Age influence on the immune system. Advances in Immunology 29, 287–330.CrossRefGoogle ScholarPubMed
Manoussakis, MN, Tzioufas, AG, Silis, MP, Pange, PJE, Evenos, J & Moutsopoulos, HM (1987) High prevalence of anti cardiolipin and other auto antibodies in a healthy elderly population. Immunology 69, 557–565.Google Scholar
Mazari, L & Lesourd, B (1998) Nutritional influences on immune response in healthy aged persons. Mechanism of Ageing and Development (In the Press).Google Scholar
Mbawuike, IN, Acuna, CL, Walz, KC, Atmar, RL, Greenberg, SB & Couch, RB (1997) Cytokines and impaired CD8+ CTL activity among elderly persons and the enhancing effect of IL-12. Mechanism of Ageing and Development 94, 25–39.Google Scholar
Meydani, SN, Barklund, MP, Lui, S, Meydani, N & Miller, RA (1990) Vitamin E supplementation enhances cell-mediated immunity in healthy elderly. American Journal of Clinical Nutrition 52, 557–563.Google Scholar
Meydani, SN, Wu, D, Santos, MS & Hayek, MG (1995) Antioxidants and immune response in aged persons: overview of the present evidence. American Journal of Clinical Nutrition 62, Suppl., 1462S–1476S.Google Scholar
Miller, RA, Garcia, G, Kirk, CJ & Witkowski, JM (1997) Early activation defects in T lymphocytes from aged mice. Immunological Reviews 160, 79–90.Google Scholar
Monget, AM (1992) Effet de la supplémentation en vitamines antioxydantes (beta carotène, vitamines C et E) et/ou en oligo éléments antioxydants (zinc et sélenium) sur l'immunité, la résistance aux infections, la morbidité et la mortalité chez le sujet âgé institutionnalisé: relations avec le métabolisme des radicaux libres (Effect of antioxidant supplementation using a combination of vitamins (β-carotene, vitamins C and E) and/or trace-elements (zinc and selenium) on immunity, infection evolution, morbidity and mortality in institutionalized old patients: relationships with free-radical metabolism). PhD Thesis, Université de Paris VII.Google Scholar
Monget, AL, Richard, MJ, Cournot, MP, Arnaid, J, Galan, P, Preziosi, P, Hercberth, B, Favier, A, Hercberg, S & the Gériatrie Min. Vit. Aox Network (1996) Effect of 6 months supplementation with different combinations of an association of antioxidant nutrients on biochemical parameters and markers of the antioxidant defence system in the elderly. European Journal of Clinical Nutrition 50, 443–449.Google ScholarPubMed
Mosmann, TR & Coffman, RL (1989) Th1 and Th2 cells: different patterns of lymphokine secretion lead to different functional properties. Annual Review of Immunology 7, 145–173.Google Scholar
Moulias, R, Devillechabrolle, A, Congy, F, Wang, A, Marescot, M & Lesourd, B (1985 a) Low prealbumin: a correlate of immunodeficiency in elderly patients. In Nutrition, Immunity and Illness in the Elderly, pp. 165–172 [Chandra, RK, editor]. London: Pergamon Press.Google Scholar
Moulias, R, Devillechabrolle, A, Lesourd, B, Proust, J, Marescot, MR, Doumerc, S, Favre-Berrone, M, Congy, F & Wang, A (1985 b) Respective roles of immune nutritional factors in the priming of the immune responses in the elderly. Mechanism of Ageing and Development 31, 3–137.Google Scholar
Moulias, R, Lesourd, B, Mélani, M, Thiollet, M, Deslandes, D & Nafziger, J (1988) T lymphocytes subsets changes during bacterial infections in the elderly. In Trends in Biomedical Gerontology, vol. 1, pp.179–180 [Steinhagen-Thiessen, E and Knook, DL, editors]. New York Pergamon Press.Google Scholar
Moulias, R, Meaume, S, Salvatore, R, Faucher-Chabert, N & Lesourd, B (1993) Immunité, nutrition et infection respiratoire chez le sujet âgé (Immunity, nutrition and lung infections in aged subjects). Médecine et Hygiène 51, 2498–2502.Google Scholar
Mountz, JD & Hsu, H-C (1997) Clinical features associated with correction of T-cell senescence: increased acute-phase response amyloidosis and arthritis. Developmental and Comparative Immunology 21, 509–523.CrossRefGoogle ScholarPubMed
Mowe, W, Behmer, T & Kindt, E (1994) Reduced nutritional status in an elderly population (> 70 y) is probable before disease and possibly contributes to the development of disease. American Journal of Clinical Nutrition 59, 317–324.Google Scholar
Munoz, C, Arévalo, M, Lopez, L & Schlesinger, L (1994) Impaired interleukin-1 and tumor necrosis factor production in protein-calorie malnutrition. Nutrition Research 14, 347–352.Google Scholar
Murasko, DM, Nelson, BS, Silver, R, Matour, D & Kaye, D (1986) Immunologic response in an elderly population with a mean age of 85. American Journal of Medicine 81, 612–618.Google Scholar
Murasko, DM, Weiner, P & Kaye, D (1987) Decline in mitogen induced proliferation of lymphocytes with increasing age. Clinical Experimental Immunology 70, 440–448.Google Scholar
Mysliwska, J, Bryl, E, Foerster, J & Myslinski, A (1998) Increase of interleukin 6 and decrease of interleukin 2 production during the ageing process are influenced by the health status. Mechanism of Ageing and Development 100, 313–328.Google Scholar
Nafziger, J, Bessege, JP, Guillosson, JJ, Damais, C & Lesourd, B (1993) Decreased capacity of IL-1 production by monocytes of infected elderly patients. Aging, Immunology and Infectious Diseases 4, 25–34.Google Scholar
Nagel, JE, Chopra, RK, Chrest, FJ, McCoy, MT, Schneider, EL, Holbrook, NJ & Adler, WH (1988) Decreased proliferation interleukin 2 synthesis and interleukin 2 receptor expression are accompanied by decreased mRNA expression, in phytohemagglutinin-stimulated cells from elderly donors. Journal of Clinical Investigation 81, 1096–1102.CrossRefGoogle ScholarPubMed
Nagelkerken, L, Hertogh-Huijbregts, A, Dobber, R & Dräger, A (1991) Age-related changes in lymphokine production related to a decreased number of CD45Rbohi CD4+ T cells. European Journal of Immunology 21, 273–281.Google Scholar
Nakayama, KI, Nakayama, K, Negishi, I, Kuida, K, Louie, MC, Kanagawa, O, Nakauchi, H & Loh, DY (1994) Requirement for CD8 beta chain in positive selection of CD8 lineage T cells. Science 263, 1131–1133.Google Scholar
Openshaw, P, Murphy, EE, Hosken, NA, Maino, V, Davis, K, Murphy, K & O'Garra, A (1995) Heterogeneity of intracellular cytokine synthesis at the single-cell level in polarized T helper 1 and T helper 2 populations. Journal of Experimental Medicine 182, 1357–1364.CrossRefGoogle Scholar
Payette, H, Rola-Pleszczynski, M & Ghadirian, P (1990) Nutrition factors in relation to cellular and regulatory immune variables in a free-living elderly population. American Journal of Clinical Nutrition 52, 927–932.Google Scholar
Penn, ND, Purkins, L, Kelleher, J, Heartley, RV, Masie-Taylor, BH & Belfield, PW (1991) The effect of dietary supplementation with vitamins A, C and E on cell-mediated immune function in elderly long-stay patients: a randomized, controlled trial. Age and Aging 20, 169–174.Google Scholar
Phair, JP (1988) Infections in the elderly. In Infectious Diseases in the Elderly, pp. 6–17 [Cunha, BA, editor]. Littleton, MA: PSG Publishing.Google Scholar
Phelouzat, MA, Arbogast, A, Laforge, T, Quadri, RA & Proust, JJ (1996) Excessive apoptosis of mature T lymphocytes is a characteristic feature of human immune senescence. Mechanism of Ageing and Development 88, 25–38.Google Scholar
Pike, J & Chandra, RK (1995) Effect of vitamin and trace element supplementation on immune indices in healthy elderly. International Journal of Vitamin and Nutrition Research 65, 117–121.Google ScholarPubMed
Pompidou, A, Duchet, N, Cooper, MD, Mace, B, Telvi, L, Coutance, F, Hadden, JW & Renoux, G (1985) The generation and regulation of human T lymphocytes by Imuthiol. Evidence from an in vitro differentiation induction system. International Journal of Immunopharmacology 7, 561–566.Google Scholar
Proust, J, Moulias, R, Fumeron, F, Beckkhoucha, F, Bussone, M, Schimd, M & Hors, J (1982) HLA and longevity. Tissue Antigens 19, 168–173.Google Scholar
Proust, J, Rosenzweig, P, Debouzy, C & Moulias, R (1985) Lymphopenia induced by acute bacterial infections in the elderly: a sign of age-related immune dysfunction of major prognostic significance. Gerontology 31, 178–185.CrossRefGoogle ScholarPubMed
Rabinowich, H, Goses, Y, Reshef, T & Klajman, A (1985) Interleukin 2 production and activity in aged humans. Mechanism of Ageing and Development 32, 213–226.Google Scholar
Robine, JM & Mormiche, P (1993) L'Espérance de Vie sans Incapacité Augmente (Increasing Life Expectancy without Handicaps). INSEE Publication no. 281. Paris: INSEE.Google Scholar
Roche, AF (1994) Sarcopenia: a critical review of its measurement and health-related significance in the middle-aged and elderly. American Journal of Human Biology 6, 33–42.Google Scholar
Rosenthal, AJ, McMurtry, CT, Sanders, KM, Jacobs, M, Thompson, D & Adler, RA (1997) The soluble interleukin-2 receptor predicts mortality in older hospitalized men. Journal of the American Geriatrics Society 45, 1362–1364.Google Scholar
Rudman, D & Feller, AG (1987) Protein-calorie undernutrition in the nursing home. Journal of the American Geriatrics Society 37, 173–183.Google Scholar
Sanders, ME, Maggoba, MW, Sharrow, SO, Stephany, D, Springer, TA, Young, HA & Shaw, S (1988) Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL-1, CDw29 and Pgp-1) and have enhanced IFN-γ production. Journal of Immunology 140, 1401–1407.CrossRefGoogle Scholar
Scarfiotti, C, Fabris, F, Cestaro, B & Giuliani, A (1997) Free radicals, atherosclerosis, ageing, and related dysmetabolic pathologies: pathological and clinical aspects. European Journal of Cancer Prevention 6, Suppl. 1, S31–S36.Google Scholar
Scrimshaw, N, Taylor, CE & Gordon, JE (1988) Interactions of nutrition and infection. Nutrition 4, 13–52.Google Scholar
Segal, R, Dayan, M, Globerson, A, Habut, B, Shearer, GM & Mozes, E (1997) Effect of aging on cytokine production in normal and experimental system in lupus erythematosus afflicted mice. Mechanism of Ageing and Development 96, 47–58.Google Scholar
Shearer, GM (1997) Th1/Th2 changes in ageing. Mechanism of Ageing and Development 94, 1–5.Google Scholar
Sindermann, J, Kruse, A, Frercks, HJ, Schutz, RM & Kirchner, H (1993) Investigations of the lymphokine system in elderly individuals. Mechanism of Ageing and Development 70, 149–159.Google Scholar
Siveke, JT & Hamann, A (1998) Cutting edge: T helper 1 and T helper 2 cells respond differentially to chemokines. Journal of Immunology 160, 550–554.Google Scholar
Spaulding, CC, Walford, RL & Effros, RB (1997) Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-a and IL-6 in C3B10RF1 mice. Mechanism of Ageing and Development 96, 75–88.Google Scholar
Sprenger, MJW, Mulder, PGH, Beyer, WE & Masurel, N (1991) Influenza: relation of mortality to morbidity parameters, The Netherlands. 1970–1989. Journal of Epidemiology 120, 1118–1124.Google Scholar
Talbott, MC, Miller, LT & Kerkvliet, NI (1987) Pyridoxine supplementation: effect on lymphocyte responses in elderly persons. American Journal of Clinical Nutrition 46, 659–664.Google Scholar
Thoman, ML (1997) Effects of the aged microenvironment on CD4+ T cell maturation. Mechanism of Ageing and Development 96, 75–88Google Scholar
Tosi, P, Krart, R, Luzy, P, Cintorino, M, Frankhauser, G, Hess, MW & Cottier, H (1982) Involution patterns of the human thymus. I. Size of the cortical area as a function of age. Clinical Experimental Immunology 47, 497–503.Google Scholar
Tyan, ML (1981) Marrow stem cells during development and aging. In Handbook of Immunology and Aging, pp.87–102 [Kay, MMB and Makinodan, T, editors]. New York: CRC Press.Google Scholar
Utsuyama, M, Kasai, M, Kurashima, C & Hirokawa, K (1997) Age influence on the thymic capacity to promote differentiation of T cells: induction of different composition of T cells subsets by ageing thymus. Mechanism of Ageing and Development 58, 167–177.Google Scholar
Venkatraman, JT, Attwood, VG, Turturro, A, Hart, RW & Fernandes, G (1994) Maintenance of virgin T cells and immune functions by food restriction during aging in long-lived B6D2F1 female mice. Aging, Immunology and Infectious Diseases 5, 13–26.Google Scholar
Venkatraman, JT & Fernandes, G (1994) Modulation of Aging by Food Restriction. New York: CRC Press.Google Scholar
Volberding, PA (1996) Age as a predictor of progression in HIV infection. Lancet 347, 1569–1570.Google Scholar
Wahlquist, ML (1990) Vitamins, nutrition, and aging. In Nutrition and Aging: Progress in Clinical and Biological Research, pp. 175–202 [Prinsley, DM and Sandstead, HH, editors]. New York: Alan R Liss.Google Scholar
Wakikawa, A, Utsuyama, M & Hirokawa, K (1997) Altered expression of various receptors on T cells in young and old mice after mitogenic stimulation: a flow cytometric analysis. Mechanism of Ageing and Development 94, 113–122.Google Scholar
Weksler, ME (1995) Immune senescence: deficiency or dysregulation. Nutrition Reviews 53, S3–S7.Google Scholar
Welle, S, Thornton, C & Jozefowicz, R (1993) Myofibrillar protein synthesis in young and old men. American Journal of Physiology 264, E693–E698.Google Scholar
Yarasheski, KE, Zachwieja, JJ & Bier, DM (1993) Acute effects of resistance exercise on muscle protein synthesis rate in young and elderly men and women American Journal of Physiology 265, E210–E214.Google Scholar
Yong-Xing, M, Yue, Z, Zan-Shun, W, Chuan-Fu, W, Su-Ying, C, Mao-Tong, Z, Gong-Liang, Z, Su-Qin, Z, Jian-Gang, Z, Qi, G & Lin, H (1997) HLA and longevity or aging among Shanghai Chinese. Mechanism of Ageing and Development 94, 191–198.Google Scholar
Young, VR (1990) Protein and amino acid metabolism with reference to aging and the elderly In Nutrition and Aging, pp. 279–300 [Prinsley, DM and Sandstead, HH, editors]. Amsterdam: Alan R Liss.Google Scholar
Yu, S, Abel, L & Globerson, A (1997) Thymocyte progenitors and T cell development in ageing. Mechanism of Ageing and Development 94, 103–111Google Scholar