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Aging and Disease    2012, Vol. 3 Issue (1) : 91-129     DOI:
The Role of Nutrition in Enhancing Immunity in Aging
Munkyong Pae, Simin Nikbin Meydani, Dayong Wu
Nutritional Immunology Laboratory, Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University, Boston, MA 02111, USA
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Aging is associated with declined immune function, particularly T cell-mediated activity, which contributes to increased morbidity and mortality from infectious disease and cancer in the elderly. Studies have shown that nutritional intervention may be a promising approach to reversing impaired immune function and diminished resistance to infection with aging. However, controversy exists concerning every nutritional regimen tested to date. In this article, we will review the progress of research in this field with a focus on nutrition factor information that is relatively abundant in the literature. While vitamin E deficiency is rare, intake above recommended levels can enhance T cell function in aged animals and humans. This effect is believed to contribute toward increased resistance to influenza infection in animals and reduced incidence of upper respiratory infection in the elderly. Zinc deficiency, common in the elderly, is linked to impaired immune function and increased risk for acquiring infection, which can be rectified by zinc supplementation. However, higher than recommended upper limits of zinc may adversely affect immune function. Probiotics are increasingly being recognized as an effective, immune-modulating nutritional factor. However, to be effective, they require an adequate supplementation period; additionally, their effects are strain-specific and among certain strains, a synergistic effect is observed. Increased intake of fish or n-3 PUFA may be beneficial to inflammatory and autoimmune disorders as well as to several age-related diseases. Conversely, the immunosuppressive effect of fish oils on T cell-mediated function has raised concerns regarding their impact on resistance to infection. Caloric restriction (CR) is shown to delay immunosenescence in animals, but this effect needs to be verified in humans. Timing for CR initiation may be important to determine whether CR is effective or even beneficial at all. Recent studies have suggested that CR, which is effective at improving the immune response of unchallenged animals, might compromise the host’s defense against pathogenic infection and result in higher morbidity and mortality. The studies published thus far describe a critical role for nutrition in maintaining the immune response of the aged, but they also indicate the need for a more in-depth, wholestic approach to determining the optimal nutritional strategies that would maintain a healthy immune system in the elderly and promote their resistance to infection and other immune-related diseases

Keywords Aging      Immunity      Infection      Nutrition     
Corresponding Authors: Dayong Wu   
Issue Date: 01 January 2012
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Munkyong Pae
Simin Nikbin Meydani
Dayong Wu
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Munkyong Pae,Simin Nikbin Meydani,Dayong Wu. The Role of Nutrition in Enhancing Immunity in Aging[J]. Aging and Disease, 2012, 3(1): 91-129.
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[1] Krabbe KS, Pedersen M, Bruunsgaard H(2004). Inflammatory mediators in the elderly. Exp Gerontol, 39:687-699
[2] Sarkar D, Fisher PB(2006). Molecular mechanisms of aging-associated inflammation. Cancer Lett, 236:13-23
[3] Vasto S, Candore G, Balistreri CR, Caruso M, Colonna-Romano G, Grimaldi MP, Listi F, Nuzzo D, Lio D, Caruso C(2007). Inflammatory networks in ageing, age-related diseases and longevity. Mech Ageing Dev, 128:83-91
[4] Webster RG(2000). Immunity to influenza in the elderly. Vaccine, 18:1686-1689
[5] Coquette A, Vray B, Vanderpas J(1986). Role of vitamin E in the protection of the resident macrophage membrane against oxidative damage. Arch Int Physiol Biochim, 94:S29-34
[6] 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. J Clin Invest, 81:1096-1102
[7] Roberts-Thomson IC, Whittingham S, Youngchaiyud U, Mackay IR(1974). Ageing, immune response, and mortality. Lancet, 2:368-370
[8] Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS(1990). Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol, 45:M45-48
[9] Jones SC, Clise-Dwyer K, Huston G, Dibble J, Eaton S, Haynes L, Swain SL(2008). Impact of Post-Thymic Cellular Longevity on the Development of Age-Associated CD4+ T Cell Defects. J Immunol, 180:4465-4475
[10] Swain S, Clise-Dwyer K, Haynes L(2005). Homeostasis and the age-associated defect of CD4 T cells. Semin Immunol, 17:370-377
[11] Goronzy JJ, Lee WW, Weyand CM(2007). Aging and T-cell diversity. Exp Gerontol, 42:400-406
[12] Goronzy JJ, Weyand CM(2005). T cell development and receptor diversity during aging. Curr Opin Immunol, 17:468-475
[13] Nikolich-Zugich J, Slifka MK, Messaoudi I(2004). The many important facets of T-cell repertoire diversity. Nat Rev Immunol, 4:123-132
[14] Adolfsson O, Huber BT, Meydani SN(2001). Vitamin E-enhanced IL-2 production in old mice: naive but not memory T cells show increased cell division cycling and IL-2-producing capacity. J Immunol, 167:3809-3817
[15] Larbi A, Douziech N, Dupuis G, Khalil A, Pelletier H, Guerard KP, Fulop TJr(2004). Age-associated alterations in the recruitment of signal-transduction proteins to lipid rafts in human T lymphocytes. J Leukoc Biol, 75:373-381
[16] Thoman ML, Weigle WO(1981). Lymphokines and aging: interleukin-2 production and activity in aged animals. J Immunol, 127:2102-2106
[17] Smith KA(1988). Interleukin-2: inception, impact, and implications. Science, 240:1169-1176
[18] Haynes L, Linton PJ, Eaton SM, Tonkonogy SL, Swain SL(1999). Interleukin 2, but not other common gamma chain-binding cytokines, can reverse the defect in generation of CD4 effector T cells from naive T cells of aged mice. J Exp Med, 190:1013-1024
[19] Linton PJ, Li SP, Zhang Y, Bautista B, Huynh Q, Trinh T(2005). Intrinsic versus environmental influences on T-cell responses in aging. Immunol Rev, 205:207-219
[20] Grossmann A, Rabinovitch PS, Kavanagh TJ, Jinneman JC, Gilliland LK, Ledbetter JA, Kanner SB(1995). Activation of murine T-cells via phospholipase-C gamma 1-associated protein tyrosine phosphorylation is reduced with aging. J Gerontol A Biol Sci Med Sci, 50:B205-212
[21] Miller RA, Garcia G, Kirk CJ, Witkowski JM(1997). Early activation defects in T lymphocytes from aged mice. Immunol Rev, 160:79-90
[22] Pahlavani MA(1998). T cell signaling: effect of age. Front Biosci, 3:D1120-1133
[23] Kirk CJ, Miller RA(1998). Analysis of Raf-1 activation in response to TCR activation and costimulation in murine T-lymphocytes: effect of age. Cellular Immunology, 190:33-42
[24] Pahlavani MA, Harris MD, Richardson A(1998). Activation of p21ras/MAPK signal transduction molecules decreases with age in mitogen-stimulated T cells from rats. Cell Immunol, 185:39-48
[25] Pahlavani MA, Harris MD, Richardson A(1995). The age-related decline in the induction of IL-2 transcription is correlated to changes in the transcription factor NFAT. Cell Immunol, 165:84-91
[26] Whisler RL, Beiqing L, Chen M(1996). Age-related decreases in IL-2 production by human T cells are associated with impaired activation of nuclear transcriptional factors AP-1 and NF-AT. Cell Immunol, 169:185-195
[27] Whisler RL, Chen M, Beiqing L, Carle KW(1997). Impaired induction of c-fos/c-jun genes and of transcriptional regulatory proteins binding distinct c-fos/c-jun promoter elements in activated human T cells during aging. Cell Immunol, 175:41-50
[28] Trebilcock GU, Ponnappan U(1996). Evidence for lowered induction of nuclear factor kappa B in activated human T lymphocytes during aging. Gerontology, 42:137-146
[29] Trebilcock GU, Ponnappan U(1998). Nuclear factor-kappaB induction in CD45RO+ and CD45RA+ T cell subsets during aging. Mech Ageing Dev, 102:149-163
[30] Garcia GG, Miller RA(2001). Single-cell analyses reveal two defects in peptide-specific activation of naive T cells from aged mice. J Immunol, 166:3151-3157
[31] Marko MG, Ahmed T, Bunnell SC, Wu D, Chung H, Huber BT, Meydani SN(2007). Age-associated decline in effective immune synapse formation of CD4(+) T cells is reversed by vitamin E supplementation. J Immunol, 178:1443-1449
[32] Tamir A, Eisenbraun MD, Garcia GG, Miller RA(2000). Age-dependent alterations in the assembly of signal transduction complexes at the site of T cell/APC interaction. J Immunol, 165:1243-1251
[33] Vallejo AN(2005). CD28 extinction in human T cells: altered functions and the program of T-cell senescence. Immunol Rev, 205:158-169
[34] Weng NP, Akbar AN, Goronzy J(2009). CD28(−) T cells: their role in the age-associated decline of immune function. Trends Immunol, 30:306-312
[35] Bartocci A, Maggi FM, Welker RD, Veronese F(1982). Age-related immunossuppresion: putative role of prostaglandins. Prostaglandins and Cancer, Powles TJ, Backman RS, Honn KV, Ramwell P 725-730Alan R. LissNew York
[36] Hayek MG, Meydani SN, Meydani M, Blumberg JB(1994). Age differences in eicosanoid production of mouse splenocytes: effects on mitogen-induced T-cell proliferation. J Gerentol, 49:B197-B207
[37] Meydani SN, Meydani M, Verdon CP, Shapiro AA, Blumberg JB, Hayes KC(1986). Vitamin E supplementation suppresses prostaglandin E1(2) synthesis and enhances the immune response of aged mice. Mech Ageing Dev, 34:191-201
[38] Meydani SN, Barklund MP, Liu S, Meydani M, Miller RA, Cannon JG, Morrow FD, Rocklin R, Blumberg JB(1990). Vitamin E supplementation enhances cell-mediated immunity in healthy elderly subjects. Am J Clin Nutr, 52:557-563
[39] Claycombe KJ, Wu D, Nikolova-Karakashian M, Palmer H, Beharka A, Paulson KE, Meydani SN(2002). Ceramide mediates age-associated increase in macrophage cyclooxygenase-2 expression. J Biol Chem, 277:30784-30791
[40] Hayek MG, Mura C, Wu D, Beharka AA, Han SN, Paulson KE, Hwang D, Meydani SN(1997). Enhanced expression of inducible cyclooxygenase with age in murine macrophages. J Immunol, 159:2445-2451
[41] Wu D, Marko M, Claycombe K, Paulson KE, Meydani SN(2003). Ceramide-induced and age-associated increase in macrophage COX-2 expression is mediated through up-regulation of NF-kappa B activity. J Biol Chem, 278:10983-10992
[42] Miller JP, Allman D(2003). The decline in B lymphopoiesis in aged mice reflects loss of very early B-lineage precursors. J Immunol, 171:2326-2330
[43] Min H, Montecino-Rodriguez E, Dorshkind K(2006). Effects of aging on the common lymphoid progenitor to pro-B cell transition. J Immunol, 176:1007-1012
[44] Kline GH, Hayden TA, Klinman NR(1999). B cell maintenance in aged mice reflects both increased B cell longevity and decreased B cell generation. J Immunol, 162:3342-3349
[45] Rajczy K, Vargha P, Beregi E(1986). Relationship between immunoglobulin levels and specific antibody titers in the elderly. Z Gerontol, 19:158-161
[46] Weksler ME, Szabo P(2000). The effect of age on the B-cell repertoire. J Clin Immunol, 20:240-249
[47] Howard WA, Gibson KL, Dunn-Walters DK(2006). Antibody quality in old age. Rejuvenation Res, 9:117-125
[48] Gibson KL, Wu YC, Barnett Y, Duggan O, Vaughan R, Kondeatis E, Nilsson BO, Wikby A, Kipling D, Dunn-Walters DK(2009). B-cell diversity decreases in old age and is correlated with poor health status. Aging Cell, 8:18-25
[49] Hijmans W, Radl J, Bottazzo GF, Doniach D(1984). Autoantibodies in highly aged humans. Mech Ageing Dev, 26:83-89
[50] Silvestris F, Anderson W, Goodwin JS, Williams RCJr(1985). Discrepancy in the expression of autoantibodies in healthy aged individuals. Clin Immunol Immunopathol, 35:234-244
[51] Stacy S, Krolick KA, Infante AJ, Kraig E(2002). Immunological memory and late onset autoimmunity. Mech Ageing Dev, 123:975-985
[52] Gomez CR, Nomellini V, Faunce DE, Kovacs EJ(2008). Innate immunity and aging. Exp Gerontol, 43:718-728
[53] Kovacs EJ, Palmer JL, Fortin CF, Fulop TJr, Goldstein DR, Linton PJ(2009). Aging and innate immunity in the mouse: impact of intrinsic and extrinsic factors. Trends Immunol, 30:319-324
[54] Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM(2010). Aging of the innate immune system. Curr Opin Immunol, 22:507-513
[55] Bruunsgaard H, Pedersen M, Pedersen BK(2001). Aging and proinflammatory cytokines. Curr Opin Hematol, 8:131-136
[56] Ershler WB(1993). Interleukin-6: a cytokine for gerontologists. J Am Geriatr Soc, 41:176-181
[57] Fagiolo U, Cossarizza A, Scala E, Fanales-Belasio E, Ortolani C, Cozzi E, Monti D, Franceschi C, Paganelli R(1993). Increased cytokine production in mononuclear cells of healthy elderly people. Eur J Immunol, 23:2375-2378
[58] Forsey RJ, Thompson JM, Ernerudh J, Hurst TL, Strindhall J, Johansson B, Nilsson BO, Wikby A(2003). Plasma cytokine profiles in elderly humans. Mech Ageing Dev, 124:487-493
[59] Franceschi C, Bonafe M, Valensin S, Olivieri F, De Luca M, Ottaviani E, De Benedictis G(2000). Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci, 908:244-254
[60] Panda A, Arjona A, Sapey E, Bai F, Fikrig E, Montgomery RR, Lord JM, Shaw AC(2009). Human innate immunosenescence: causes and consequences for immunity in old age. Trends Immunol, 30:325-333
[61] Mocchegiani E, Malavolta M(2004). NK and NKT cell functions in immunosenescence. Aging Cell, 3:177-184
[62] Hatam LJ, Kayden HJ(1979). A high-performance liquid chromatographic method for the determination of tocopherol in plasma and cellular elements of the blood. J Lipid Res, 20:639-645
[63] Gebremichael A, Levy EM, Corwin LM(1984). Adherent cell requirement for the effect of vitamin E on in vitro antibody synthesis. J Nutr, 114:1297-1305
[64] Kowdley KV, Mason JB, Meydani SN, Cornwall S, Grand RJ(1992). Vitamin E deficiency and impaired cellular immunity related to intestinal fat malabsorption. Gastroenterology, 102:2139-2142
[65] Han SN, Meydani SN(1999). Vitamin E and infectious diseases in the aged. Proc Nutr Soc, 58:697-705
[66] Meydani SN, Meydani M, Blumberg JB, Leka LS, Siber G, Loszewski R, Thompson C, Pedrosa MC, Diamond RD, Stollar BD(1997). Vitamin E supplementation and in vivo immune response in healthy elderly subjects. A randomized controlled trial. Jama, 277:1380-1386
[67] Sakai S, Moriguchi S(1997). Long-term feeding of high vitamin E diet improves the decreased mitogen response of rat splenic lymphocytes with aging. J Nutr Sci Vitaminol (Tokyo)43:113-122
[68] Pallast EG, Schouten EG, de Waart FG, Fonk HC, Doekes G, von Blomberg BM, Kok FJ(1999). Effect of 50- and 100-mg vitamin E supplements on cellular immune function in noninstitutionalized elderly persons. Am J Clin Nutr, 69:1273-1281
[69] De la Fuente M, Hernanz A, Guayerbas N, Victor VM, Arnalich F(2008). Vitamin E ingestion improves several immune functions in elderly men and women. Free Radic Res, 42:272-280
[70] Meydani SN, Han SN, Wu D(2005). Vitamin E and immune response in the aged: molecular mechanisms and clinical implications. Immunol Rev, 205:269-284
[71] Wu D, Meydani SN(2008). Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention. J Leukoc Biol, 84:900-914
[72] Zhang W, Trible RP, Zhu M, Liu SK, McGlade CJ, Samelson LE(2000). Association of Grb2, Gads, and phospholipase C-gamma 1 with phosphorylated LAT tyrosine residues. Effect of LAT tyrosine mutations on T cell angigen receptor-mediated signaling. J Biol Chem, 275:23355-23361
[73] Paz PE, Wang S, Clarke H, Lu X, Stokoe D, Abo A(2001). Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells. Biochem J, 356:461-471
[74] Marko MG, Pang HJ, Ren Z, Azzi A, Huber BT, Bunnell SC, Meydani SN(2009). Vitamin E reverses impaired linker for activation of T cells activation in T cells from aged C57BL/6 mice. J Nutr, 139:1192-1197
[75] Beharka AA, Wu D, Han SN, Meydani SN(1997). Macrophage PGE2 production contributes to the age-associated decrease in T cell function which is reversed by dietary antioxidants. Mech Ageing Dev, 93:59-77
[76] Franklin RA, Arkins S, Li YM, Kelley KW(1993). Macrophages suppress lectin-induced proliferation of lymphocytes from aged rats. Mech Ageing Dev, 67:33-46
[77] Wu D, Mura C, Beharka AA, Han SN, Paulson KE, Hwang D, Meydani SN(1998). Age-associated increase in PGE2 synthesis and COX activity in murine macrophages is reversed by vitamin E. Am J Physiol, 275:C661-668
[78] Jiang Q, Elson-Schwab I, Courtemanche C, Ames BN(2000). gamma-tocopherol and its major metabolite, in contrast to alpha-tocopherol, inhibit cyclooxygenase activity in macrophages and epithelial cells. Proc Natl Acad Sci U S A, 97:11494-11499
[79] O'Leary KA, de Pascual-Tereasa S, Needs PW, Bao YP, NM OB, Williamson G(2004). Effect of flavonoids and vitamin E on cyclooxygenase-2 (COX-2) transcription. Mutat Res, 551:245-254
[80] Beharka AA, Wu D, Serafini M, Meydani SN(2002). Mechanism of vitamin E inhibition of cyclooxygenase activity in macrophages from old mice: role of peroxynitrite. Free Radic Boil Med, 32:503-511
[81] Landino LM, Crews BC, Timmons MD, Morrow JD, Marnett LJ(1996). Peroxynitrite, the coupling product of nitric oxide and superoxide, activates prostaglandin biosynthesis. Proc Natl Acad Sci U S A, 93:15069-15074
[82] Belisle SE, Leka LS, Dallal GE, Jacques PF, Delgado-Lista J, Ordovas JM, Meydani SN(2008). Cytokine response to vitamin E supplementation is dependent on pre-supplementation cytokine levels. Biofactors, 33:191-200
[83] Belisle SE, Leka LS, Delgado-Lista J, Jacques PF, Ordovas JM, Meydani SN(2009). Polymorphisms at cytokine genes may determine the effect of vitamin E on cytokine production in the elderly. J Nutr, 139:1855-1860
[84] Louis E, Franchimont D, Piron A, Gevaert Y, Schaaf-Lafontaine N, Roland S, Mahieu P, Malaise M, De Groote D, Louis R, Belaiche J(1998). Tumour necrosis factor (TNF) gene polymorphism influences TNF-alpha production in lipopolysaccharide (LPS)-stimulated whole blood cell culture in healthy humans. Clin Exp Immunol, 113:401-406
[85] Wilson AG, Symons JA, McDowell TL, McDevitt HO, Duff GW(1997). Effects of a polymorphism in the human tumor necrosis factor alpha promoter on transcriptional activation. Proc Natl Acad Sci U S A, 94:3195-3199
[86] Crossley KB, Peterson PK(1996). Infections in the elderly. Clin Infect Dis, 22:209-215
[87] Farber BF, Brennen C, Puntereri AJ, Brody JP(1984). A prospective study of nosocomial infections in a chronic care facility. J Am Geriatr Soc, 32:499-502
[88] Mehr DR, Foxman B, Colombo P(1992). Risk factors for mortality from lower respiratory infections in nursing home patients. J Fam Pract, 34:585-591
[89] Ely KH, Roberts AD, Kohlmeier JE, Blackman MA, Woodland DL(2007). Aging and CD8+ T cell immunity to respiratory virus infections. Exp Gerontol, 42:427-431
[90] Gavazzi G, Krause KH(2002). Ageing and infection. Lancet Infect Dis, 2:659-666
[91] Hayek MG, Taylor SF, Bender BS, Han SN, Meydani M, Smith DE, Eghtesada S, Meydani SN(1997). Vitamin E supplementation decreases lung virus titers in mice infected with influenza. J Infect Dis, 176:273-276
[92] Han SN, Wu D, Ha WK, Beharka A, Smith DE, Bender BS, Meydani SN(2000). Vitamin E supplementation increases T helper 1 cytokine production in old mice infected with influenza virus. Immunology, 100:487-493
[93] Chavance M, Herbeth B, Fournier C, Janot C, Vernhes G(1989). Vitamin status, immunity and infections in an elderly population. Eur J Clin Nutr, 43:827-835
[94] Meydani SN, Leka LS, Fine BC, Dallal GE, Keusch GT, Singh MF, Hamer DH(2004). Vitamin E and respiratory tract infections in elderly nursing home residents: a randomized controlled trial. Jama, 292:828-836
[95] Hemila H, Kaprio J(2011). Subgroup analysis of large trials can guide further research: a case study of vitamin E and pneumonia. Clin Epidemiol, 3:51-59
[96] Hemila H, Virtamo J, Albanes D, Kaprio J(2004). Vitamin E and beta-carotene supplementation and hospital-treated pneumonia incidence in male smokers. Chest, 125:557-565
[97] Hemila H, Virtamo J, Albanes D, Kaprio J(2006). The effect of vitamin E on common cold incidence is modified by age, smoking and residential neighborhood. J Am Coll Nutr, 25:332-339
[98] Graat JM, Schouten EG, Kok FJ(2002). Effect of daily vitamin E and multivitamin-mineral supplementation on acute respiratory tract infections in elderly persons: a randomized controlled trial. Jama, 288:715-721
[99] Prasad AS(2009). Zinc: role in immunity, oxidative stress and chronic inflammation. Curr Opin Clin Nutr Metab Care, 12:646-652
[100] Haase H, Rink L(2009). Functional significance of zinc-related signaling pathways in immune cells. Annu Rev Nutr, 29:133-152
[101] Mitchell WA, Meng I, Nicholson SA, Aspinall R(2006). Thymic output, ageing and zinc. Biogerontology, 7:461-470
[102] Haase H, Rink L(2009). The immune system and the impact of zinc during aging. Immun Ageing, 6:9
[103] Keen CL, Gershwin ME(1990). Zinc deficiency and immune function. Annu Rev Nutr, 10:415-431
[104] Prasad AS(2000). Effects of zinc deficiency on Th1 and Th2 cytokine shifts. J Infect Dis, 182(Suppl 1):S62-68
[105] Prasad AS(2008). Zinc in human health: effect of zinc on immune cells. Mol Med, 14:353-357
[106] Fraker PJ, King LE, Laakko T, Vollmer TL(2000). The dynamic link between the integrity of the immune system and zinc status. J Nutr, 130:1399S-1406S
[107] Fischer Walker C, Black RE(2004). Zinc and the risk for infectious disease. Annu Rev Nutr, 24:255-275
[108] Dardenne M, Boukaiba N, Gagnerault MC, Homo-Delarche F, Chappuis P, Lemonnier D, Savino W(1993). Restoration of the thymus in aging mice by in vivo zinc supplementation. Clin Immunol Immunopathol, 66:127-135
[109] Mocchegiani E, Santarelli L, Muzzioli M, Fabris N(1995). Reversibility of the thymic involution and of age-related peripheral immune dysfunctions by zinc supplementation in old mice. Int J Immunopharmacol, 17:703-718
[110] Wong CP, Song Y, Elias VD, Magnusson KR, Ho E(2009). Zinc supplementation increases zinc status and thymopoiesis in aged mice. J Nutr, 139:1393-1397
[111] Cossack ZT(1989). T-lymphocyte dysfunction in the elderly associated with zinc deficiency and subnormal nucleoside phosphorylase activity: effect of zinc supplementation. Eur J Cancer Clin Oncol, 25:973-976
[112] Duchateau J, Delepesse G, Vrijens R, Collet H(1981). Beneficial effects of oral zinc supplementation on the immune response of old people. Am J Med, 70:1001-1004
[113] Wagner PA, Jernigan JA, Bailey LB, Nickens C, Brazzi GA(1983). Zinc nutriture and cell-mediated immunity in the aged. Int J Vitam Nutr Res, 53:94-101
[114] Prasad AS, Fitzgerald JT, Hess JW, Kaplan J, Pelen F, Dardenne M(1993). Zinc deficiency in elderly patients. Nutrition, 9:218-224
[115] Prasad AS, Bao B, Beck FW, Sarkar FH(2006). Correction of interleukin-2 gene expression by in vitro zinc addition to mononuclear cells from zinc-deficient human subjects: a specific test for zinc deficiency in humans. Transl Res, 148:325-333
[116] 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. J Am Coll Nutr, 9:214-225
[117] Bogden JD, Oleske JM, Lavenhar MA, Munves EM, Kemp FW, Bruening KS, Holding KJ, Denny TN, Guarino MA, Krieger LM(1988). Zinc and immunocompetence in elderly people: effects of zinc supplementation for 3 months. Am J Clin Nutr, 48:655-663
[118] Fortes C, Forastiere F, Agabiti N, Fano V, Pacifici R, Virgili F, Piras G, Guidi L, Bartoloni C, Tricerri A, Zuccaro P, Ebrahim S, Perucci CA(1998). The effect of zinc and vitamin A supplementation on immune response in an older population. J Am Geriatr Soc, 46:19-26
[119] Kahmann L, Uciechowski P, Warmuth S, Malavolta M, Mocchegiani E, Rink L(2006). Effect of improved zinc status on T helper cell activation and TH1/TH2 ratio in healthy elderly individuals. Biogerontology, 7:429-435
[120] Bach JF, Papiernik M, Levasseur P, Dardenne M, Barois A, Le Brigand H(1972). Evidence for a serum-factor secreted by the human thymus. Lancet, 2:1056-1058
[121] Iwata T, Incefy GS, Tanaka T, Fernandes G, Menendez-Botet CJ, Pih K, Good RA(1979). Circulating thymic hormone levels in zinc deficiency. Cell Immunol, 47:100-105
[122] Dardenne M, Pleau JM, Nabarra B, Lefrancier P, Derrien M, Choay J, Bach JF(1982). Contribution of zinc and other metals to the biological activity of the serum thymic factor. Proc Natl Acad Sci U S A, 79:5370-5373
[123] Boukaiba N, Flament C, Acher S, Chappuis P, Piau 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. Am J Clin Nutr, 57:566-572
[124] Mocchegiani E, Muzzioli M, Giacconi R, Cipriano C, Gasparini N, Franceschi C, Gaetti R, Cavalieri E, Suzuki H(2003). Metallothioneins/PARP-1/IL-6 interplay on natural killer cell activity in elderly: parallelism with nonagenarians and old infected humans. Effect of zinc supply Mech Ageing Dev, 124:459-468
[125] Muzzioli M, Mocchegiani E, Bressani N, Bevilacqua P, Fabris N(1992). In vitro restoration by thymulin of NK activity of cells from old mice. Int J Immunopharmacol, 14:57-61
[126] Ravaglia G, Forti P, Maioli F, Bastagli L, Facchini A, Mariani E, Savarino L, Sassi S, Cucinotta D, Lenaz G(2000). Effect of micronutrient status on natural killer cell immune function in healthy free-living subjects aged >/=90 y. Am J Clin Nutr, 71:590-598
[127] Mocchegiani E, Giacconi R, Costarelli L, Muti E, Cipriano C, Tesei S, Pierpaoli S, Giuli C, Papa R, Marcellini F, Gasparini N, Pierandrei R, Piacenza F, Mariani E, Monti D, Dedoussis G, Kanoni S, Herbein G, Fulop T, Rink L, Jajte J, Malavolta M(2008). Zinc deficiency and IL-6 -174G/C polymorphism in old people from different European countries: effect of zinc supplementation. ZINCAGE study Exp Gerontol, 43:433-444
[128] Mariani E, Neri S, Cattini L, Mocchegiani E, Malavolta M, Dedoussis GV, Kanoni S, Rink L, Jajte J, Facchini A(2008). Effect of zinc supplementation on plasma IL-6 and MCP-1 production and NK cell function in healthy elderly: interactive influence of +647 MT1a and −174 IL-6 polymorphic alleles. Exp Gerontol, 43:462-471
[129] Gardner EM, Bernstein ED, Popoff KA, Abrutyn E, Gross P, Murasko DM(2000). Immune response to influenza vaccine in healthy elderly: lack of association with plasma beta-carotene, retinol, alpha-tocopherol, or zinc. Mech Ageing Dev, 117:29-45
[130] Provinciali M, Montenovo A, Di Stefano G, Colombo M, Daghetta L, Cairati M, Veroni C, Cassino R, Della Torre F, Fabris N(1998). Effect of zinc or zinc plus arginine supplementation on antibody titre and lymphocyte subsets after influenza vaccination in elderly subjects: a randomized controlled trial. Age Ageing, 27:715-722
[131] Chandra RK(1984). Excessive intake of zinc impairs immune responses. Jama, 252:1443-1446
[132] Cakman I, Kirchner H, Rink L(1997). Zinc supplementation reconstitutes the production of interferon-alpha by leukocytes from elderly persons. J Interferon Cytokine Res, 17:469-472
[133] Wellinghausen N, Martin M, Rink L(1997). Zinc inhibits interleukin-1-dependent T cell stimulation. Eur J Immunol, 27:2529-2535
[134] Bao B, Prasad A, Beck FW, Suneja A, Sarkar F(2006). Toxic effect of zinc on NF-kappaB, IL-2, IL-2 receptor alpha, and TNF-alpha in HUT-78 (Th(0)) cells. Toxicol Lett, 166:222-228
[135] Tanaka S, Akaishi E, Hosaka K, Okamura S, Kubohara Y(2005). Zinc ions suppress mitogen-activated interleukin-2 production in Jurkat cells. Biochem Biophys Res Commun, 335:162-167
[136] Ruel MT, Rivera JA, Santizo MC, Lonnerdal B, Brown KH(1997). Impact of zinc supplementation on morbidity from diarrhea and respiratory infections among rural Guatemalan children. Pediatrics, 99:808-813
[137] Bao B, Prasad AS, Beck FW, Snell D, Suneja A, Sarkar FH, Doshi N, Fitzgerald JT, Swerdlow P(2008). Zinc supplementation decreases oxidative stress, incidence of infection, and generation of inflammatory cytokines in sickle cell disease patients. Transl Res, 152:67-80
[138] Girodon F, Lombard M, Galan P, Brunet-Lecomte P, Monget AL, Arnaud J, Preziosi P, Hercberg S(1997). Effect of micronutrient supplementation on infection in institutionalized elderly subjects: a controlled trial. Ann Nutr Metab, 41:98-107
[139] Girodon F, Galan P, Monget AL, Boutron-Ruault MC, Brunet-Lecomte P, Preziosi P, Arnaud J, Manuguerra JC, Herchberg S(1999). Impact of trace elements and vitamin supplementation on immunity and infections in institutionalized elderly patients: a randomized controlled trial. MIN VIT AOX geriatric network Arch Intern Med, 159:748-754
[140] Prasad AS, Beck FW, Bao B, Fitzgerald JT, Snell DC, Steinberg JD, Cardozo LJ(2007). Zinc supplementation decreases incidence of infections in the elderly: effect of zinc on generation of cytokines and oxidative stress. Am J Clin Nutr, 85:837-844
[141] Meydani SN, Barnett JB, Dallal GE, Fine BC, Jacques PF, Leka LS, Hamer DH(2007). Serum zinc and pneumonia in nursing home elderly. Am J Clin Nutr, 86:1167-1173
[142] Brooks WA, Santosham M, Naheed A, Goswami D, Wahed MA, Diener-West M, Faruque AS, Black RE(2005). Effect of weekly zinc supplements on incidence of pneumonia and diarrhoea in children younger than 2 years in an urban, low-income population in Bangladesh: randomised controlled trial. Lancet, 366:999-1004
[143] Guarner F, Schaafsma GJ(1998). Probiotics. Int J Food Microbiol, 39:237-238
[144] de Moreno de LeBlanc A, Chaves S, Carmuega E, Weill R, Antoine J, Perdigon G(2008). Effect of long-term continuous consumption of fermented milk containing probiotic bacteria on mucosal immunity and the activity of peritoneal macrophages. Immunobiology, 213:97-108
[145] Delcenserie V, Martel D, Lamoureux M, Amiot J, Boutin Y, Roy D(2008). Immunomodulatory effects of probiotics in the intestinal tract. Curr Issues Mol Biol, 10:37-54
[146] Mazanec MB, Nedrud JG, Kaetzel CS, Lamm ME(1993). A three-tiered view of the role of IgA in mucosal defense. Immunol Today, 14:430-435
[147] Beharka AA, Paiva S, Leka LS, Ribaya-Mercado JD, Russell RM, Nibkin Meydani S(2001). Effect of age on the gastrointestinal-associated mucosal immune response of humans. J Gerontol A Biol Sci Med Sci, 56:B218-223
[148] Fujihashi K, Kiyono H(2009). Mucosal immunosenescence: new developments and vaccines to control infectious diseases. Trends Immunol, 30:334-343
[149] Galdeano CM, Perdigon G(2004). Role of viability of probiotic strains in their persistence in the gut and in mucosal immune stimulation. J Appl Microbiol, 97:673-681
[150] Thomas CM, Versalovic J(2010). Probiotics-host communication: Modulation of signaling pathways in the intestine. Gut Microbes, 1:1-16
[151] Macpherson AJ, Uhr T(2004). Induction of protective IgA by intestinal dendritic cells carrying commensal bacteria. Science, 303:1662-1665
[152] Muscettola M, Massai L, Tanganelli C, Grasso G(1994). Effects of lactobacilli on interferon production in young and aged mice. Ann N Y Acad Sci, 717:226-232
[153] Baba N, Samson S, Bourdet-Sicard R, Rubio M, Sarfati M(2009). Selected commensal-related bacteria and Toll-like receptor 3 agonist combinatorial codes synergistically induce interleukin-12 production by dendritic cells to trigger a T helper type 1 polarizing programme. Immunology, 128:e523-531
[154] Rescigno M, Urbano M, Valzasina B, Francolini M, Rotta G, Bonasio R, Granucci F, Kraehenbuhl JP, Ricciardi-Castagnoli P(2001). Dendritic cells express tight junction proteins and penetrate gut epithelial monolayers to sample bacteria. Nat Immunol, 2:361-367
[155] Davidson LE, Fiorino AM, Snydman DR, Hibberd PL(2011). Lactobacillus GG as an immune adjuvant for live-attenuated influenza vaccine in healthy adults: a randomized double-blind placebo-controlled trial. Eur J Clin Nutr, 65:501-507
[156] Elmadfa I, Klein P, Meyer AL(2010). Immune-stimulating effects of lactic acid bacteria in vivo and in vitro. Proc Nutr Soc, 69:416-420
[157] Vidal K, Benyacoub J, Moser M, Sanchez-Garcia J, Serrant P, Segura-Roggero I, Reuteler G, Blum S(2008). Effect of Lactobacillus paracasei NCC2461 on antigen-specific T-cell mediated immune responses in aged mice. Rejuvenation Res, 11:957-964
[158] Fu YR, Yi ZJ, Pei JL, Guan S(2010). Effects of Bifidobacterium bifidum on adaptive immune senescence in aging mice. Microbiol Immunol, 54:578-583
[159] Bouillanne O, Morineau G, Dupont C, Coulombel I, Vincent JP, Nicolis I, Benazeth S, Cynober L, Aussel C(2005). Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients. Am J Clin Nutr, 82:777-783
[160] Chandra RK(1989). Nutritional regulation of immunity and risk of infection in old age. Immunology, 67:141-147
[161] Kaburagi T, Yamano T, Fukushima Y, Yoshino H, Mito N, Sato K(2007). Effect of Lactobacillus johnsonii La1 on immune function and serum albumin in aged and malnourished aged mice. Nutrition, 23:342-350
[162] Yang HY, Liu SL, Ibrahim SA, Zhao L, Jiang JL, Sun WF, Ren FZ(2009). Oral administration of live Bifidobacterium substrains isolated from healthy centenarians enhanced immune function in BALB/c mice. Nutr Res, 29:281-289
[163] Lee Y, Lee TS(2005). Enhancement in ex vivo phagocytic capacity of peritoneal leukocytes in mice by oral delivery of various lactic-acid-producing bacteria. Curr Microbiol, 50:24-27
[164] Tsai YT, Cheng PC, Fan CK, Pan TM(2008). Time-dependent persistence of enhanced immune response by a potential probiotic strain Lactobacillus paracasei subsp paracasei NTU 101 Int J Food Microbiol, 128:219-225
[165] Fernandez-Gutierrez B, Jover JA, De Miguel S, Hernandez-Garcia C, Vidan MT, Ribera JM, Banares A, Serra JA(1999). Early lymphocyte activation in elderly humans: impaired T and T-dependent B cell responses. Exp Gerontol, 34:217-229
[166] Linton PJ, Haynes L, Klinman NR, Swain SL(1996). Antigen-independent changes in naive CD4 T cells with aging. J Exp Med, 184:1891-1900
[167] Arunachalam K, Gill HS, Chandra RK(2000). Enhancement of natural immune function by dietary consumption of Bifidobacterium lactis (HN019)Eur J Clin Nutr, 54:263-267
[168] Gill HS, Rutherfurd KJ, Cross ML(2001). Dietary probiotic supplementation enhances natural killer cell activity in the elderly: an investigation of age-related immunological changes. J Clin Immunol, 21:264-271
[169] Gill HS, Rutherfurd KJ, Cross ML, Gopal PK(2001). Enhancement of immunity in the elderly by dietary supplementation with the probiotic Bifidobacterium lactis HN019. Am J Clin Nutr, 74:833-839
[170] Fang H, Elina T, Heikki A, Seppo S(2000). Modulation of humoral immune response through probiotic intake. FEMS Immunol Med Microbiol, 29:47-52
[171] Pelto L, Isolauri E, Lilius EM, Nuutila J, Salminen S(1998). Probiotic bacteria down-regulate the milk-induced inflammatory response in milk-hypersensitive subjects but have an immunostimulatory effect in healthy subjects. Clin Exp Allergy, 28:1474-1479
[172] Chiang BL, Sheih YH, Wang LH, Liao CK, Gill HS(2000). Enhancing immunity by dietary consumption of a probiotic lactic acid bacterium (Bifidobacterium lactis HN019): optimization and definition of cellular immune responses. Eur J Clin Nutr, 54:849-855
[173] Sheih YH, Chiang BL, Wang LH, Liao CK, Gill HS(2001). Systemic immunity-enhancing effects in healthy subjects following dietary consumption of the lactic acid bacterium Lactobacillus rhamnosus HN001. J Am Coll Nutr, 20:149-156
[174] Parra MD, Martinez de Morentin BE, Cobo JM, Mateos A, Martinez JA(2004). Daily ingestion of fermented milk containing Lactobacillus casei DN114001 improves innate-defense capacity in healthy middle-aged people. J Physiol Biochem, 60:85-91
[175] Goodwin K, Viboud C, Simonsen L(2006). Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine, 24:1159-1169
[176] Boge T, Remigy M, Vaudaine S, Tanguy J, Bourdet-Sicard R, van der Werf S(2009). A probiotic fermented dairy drink improves antibody response to influenza vaccination in the elderly in two randomised controlled trials. Vaccine, 27:5677-5684
[177] Borchers AT, Keen CL, Gershwin ME(2002). The influence of yogurt/Lactobacillus on the innate and acquired immune response. Clin Rev Allergy Immunol, 22:207-230
[178] Kekkonen RA, Lummela N, Karjalainen H, Latvala S, Tynkkynen S, Jarvenpaa S, Kautiainen H, Julkunen I, Vapaatalo H, Korpela R(2008). Probiotic intervention has strain-specific anti-inflammatory effects in healthy adults. World J Gastroenterol, 14:2029-2036
[179] Spanhaak S, Havenaar R, Schaafsma G(1998). The effect of consumption of milk fermented by Lactobacillus casei strain Shirota on the intestinal microflora and immune parameters in humans. Eur J Clin Nutr, 52:899-907
[180] Gill HS, Shu Q, Lin H, Rutherfurd KJ, Cross ML(2001). Protection against translocating Salmonella typhimurium infection in mice by feeding the immuno-enhancing probiotic Lactobacillus rhamnosus strain HN001. Med Microbiol Immunol, 190:97-104
[181] Shu Q, Lin H, Rutherfurd KJ, Fenwick SG, Prasad J, Gopal PK, Gill HS(2000). Dietary Bifidobacterium lactis (HN019) enhances resistance to oral Salmonella typhimurium infection in mice. Microbiol Immunol, 44:213-222
[182] de Waard R, Garssen J, Vos JG, Claassen E(2002). Modulation of delayed-type hypersensitivity and acquired cellular resistance by orally administered viable indigenous lactobacilli in Listeria monocytogenes infected Wistar rats. Lett Appl Microbiol, 35:256-260
[183] Bunout D, Barrera G, Hirsch S, Gattas V, de la Maza MP, Haschke F, Steenhout P, Klassen P, Hager C, Avendano M, Petermann M, Munoz C(2004). Effects of a nutritional supplement on the immune response and cytokine production in free-living Chilean elderly. JPEN J Parenter Enteral Nutr, 28:348-354
[184] Fukushima Y, Miyaguchi S, Yamano T, Kaburagi T, Iino H, Ushida K, Sato K(2007). Improvement of nutritional status and incidence of infection in hospitalised, enterally fed elderly by feeding of fermented milk containing probiotic Lactobacillus johnsonii La1 (NCC533)Br J Nutr, 98:969-977
[185] Guillemard E, Tondu F, Lacoin F, Schrezenmeir J(2010). Consumption of a fermented dairy product containing the probiotic Lactobacillus casei DN-114001 reduces the duration of respiratory infections in the elderly in a randomised controlled trial. Br J Nutr, 103:58-68
[186] Makino S, Ikegami S, Kume A, Horiuchi H, Sasaki H, Orii N(2010). Reducing the risk of infection in the elderly by dietary intake of yoghurt fermented with Lactobacillus delbrueckii ssp bulgaricus OLL1073R-1. Br J Nutr, 104:998-1006
[187] de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C, Ott S, Hampe J, Schreiber S, Heller K, Schrezenmeir J(2005). Effect of Lactobacillus gasseri PA 16/8, Bifidobacterium longum SP 07/3, B. bifidum MF 20/5 on common cold episodes: a double blind, randomized, controlled trial. Clin Nutr, 24:481-491
[188] de Vrese M, Winkler P, Rautenberg P, Harder T, Noah C, Laue C, Ott S, Hampe J, Schreiber S, Heller K, Schrezenmeir J(2006). Probiotic bacteria reduced duration and severity but not the incidence of common cold episodes in a double blind, randomized, controlled trial. Vaccine, 24:6670-6674
[189] Berggren A, Lazou Ahren I, Larsson N, Onning G(2011). Randomised, double-blind and placebo-controlled study using new probiotic lactobacilli for strengthening the body immune defence against viral infections. Eur J Nutr, 50:203-210
[190] Galli C, Calder PC(2009). Effects of fat and fatty acid intake on inflammatory and immune responses: a critical review. Ann Nutr Metab, 55:123-139
[191] Fernandes G(2008). Progress in nutritional immunology. Immunol Res, 40:244-261
[192] Fritsche K(2007). Important differences exist in the dose-response relationship between diet and immune cell fatty acids in humans and rodents. Lipids, 42:961-979
[193] Sijben JW, Calder PC(2007). Differential immunomodulation with long-chain n-3 PUFA in health and chronic disease. Proc Nutr Soc, 66:237-259
[194] Shaikh SR, Edidin M(2006). Polyunsaturated fatty acids, membrane organization, T cells, and antigen presentation. Am J Clin Nutr, 84:1277-1289
[195] Kim W, Khan NA, McMurray DN, Prior IA, Wang N, Chapkin RS(2010). Regulatory activity of polyunsaturated fatty acids in T-cell signaling. Prog Lipid Res, 49:250-261
[196] Calder PC(2010). The 2008 ESPEN Sir David Cuthbertson Lecture: Fatty acids and inflammation--from the membrane to the nucleus and from the laboratory bench to the clinic. Clin Nutr, 29:5-12
[197] Serhan CN, Chiang N, Van Dyke TE(2008). Resolving inflammation: dual anti-inflammatory and pro-resolution lipid mediators. Nat Rev Immunol, 8:349-361
[198] Kohli P, Levy BD(2009). Resolvins and protectins: mediating solutions to inflammation. Br J Pharmacol, 158:960-971
[199] Kew S, Banerjee T, Minihane AM, Finnegan YE, Muggli R, Albers R, Williams CM, Calder PC(2003). Lack of effect of foods enriched with plant- or marine-derived n-3 fatty acids on human immune function. Am J Clin Nutr, 77:1287-1295
[200] Wallace FA, Miles EA, Calder PC(2003). Comparison of the effects of linseed oil and different doses of fish oil on mononuclear cell function in healthy human subjects. Br J Nutr, 89:679-689
[201] Fowler KH, Chapkin RS, McMurray DN(1993). Effects of purified dietary n-3 ethyl esters on murine T lymphocyte function. J Immunol, 151:5186-5197
[202] Payan DG, Wong MY, Chernov-Rogan T, Valone FH, Pickett WC, Blake VA, Gold WM, Goetzl EJ(1986). Alterations in human leukocyte function induced by ingestion of eicosapentaenoic acid. J Clin Immunol, 6:402-410
[203] Wu D, Meydani SN, Meydani M, Hayek MG, Huth P, Nicolosi RJ(1996). Immunologic effects of marine- and plant-derived n-3 polyunsaturated fatty acids in nonhuman primates. Am J Clin Nutr, 63:273-280
[204] Pompos LJ, Fritsche KL(2002). Antigen-driven murine CD4+ T lymphocyte proliferation and interleukin-2 production are diminished by dietary (n-3) polyunsaturated fatty acids. J Nutr, 132:3293-3300
[205] Zhang P, Kim W, Zhou L, Wang N, Ly LH, McMurray DN, Chapkin RS(2006). Dietary fish oil inhibits antigen-specific murine Th1 cell development by suppression of clonal expansion. J Nutr, 136:2391-2398
[206] Meydani SN, Lichtenstein AH, Cornwall S, Meydani M, Goldin BR, Rasmussen H, Dinarello CA, Schaefer EJ(1993). Immunologic effects of national cholesterol education panel step-2 diets with and without fish-derived N-3 fatty acid enrichment. J Clin Invest, 92:105-113
[207] Chapkin RS, Kim W, Lupton JR, McMurray DN(2009). Dietary docosahexaenoic and eicosapentaenoic acid: emerging mediators of inflammation. Prostaglandins Leukot Essent Fatty Acids, 81:187-191
[208] Kim W, Fan YY, Barhoumi R, Smith R, McMurray DN, Chapkin RS(2008). n-3 polyunsaturated fatty acids suppress the localization and activation of signaling proteins at the immunological synapse in murine CD4+ T cells by affecting lipid raft formation. J Immunol, 181:6236-6243
[209] Yog R, Barhoumi R, McMurray DN, Chapkin RS(2010). n-3 polyunsaturated fatty acids suppress mitochondrial translocation to the immunologic synapse and modulate calcium signaling in T cells. J Immunol, 184:5865-5873
[210] Meydani SN, Endres S, Woods MM, Goldin BR, Soo C, Morrill-Labrode A, Dinarello CA, Gorbach SL(1991). Oral (n-3) fatty acid supplementation suppresses cytokine production and lymphocyte proliferation: comparison between young and older women. J Nutr, 121:547-555
[211] Bechoua S, Dubois M, Vericel E, Chapuy P, Lagarde M, Prigent AF(2003). Influence of very low dietary intake of marine oil on some functional aspects of immune cells in healthy elderly people. Br J Nutr, 89:523-531
[212] Rees D, Miles EA, Banerjee T, Wells SJ, Roynette CE, Wahle KW, Calder PC(2006). Dose-related effects of eicosapentaenoic acid on innate immune function in healthy humans: a comparison of young and older men. Am J Clin Nutr, 83:331-342
[213] Alperovich M, Neuman MI, Willett WC, Curhan GC(2007). Fatty acid intake and the risk of community-acquired pneumonia in U.S. women. Nutrition, 23:196-202
[214] Merchant AT, Curhan GC, Rimm EB, Willett WC, Fawzi WW(2005). Intake of n-6 and n-3 fatty acids and fish and risk of community-acquired pneumonia in US men. Am J Clin Nutr, 82:668-674
[215] Anderson M, Fritsche KL(2002(n-3) Fatty acids and infectious disease resistance. J Nutr, 132:3566-3576
[216] Byleveld M, Pang GT, Clancy RL, Roberts DC(2000). Fish oil feeding enhances lymphocyte proliferation but impairs virus-specific T lymphocyte cytotoxicity in mice following challenge with influenza virus. Clin Exp Immunol, 119:287-292
[217] Byleveld PM, Pang GT, Clancy RL, Roberts DC(1999). Fish oil feeding delays influenza virus clearance and impairs production of interferon-gamma and virus-specific immunoglobulin A in the lungs of mice. J Nutr, 129:328-335
[218] Schwerbrock NM, Karlsson EA, Shi Q, Sheridan PA, Beck MA(2009). Fish oil-fed mice have impaired resistance to influenza infection. J Nutr, 139:1588-1594
[219] Paul KP, Leichsenring M, Pfisterer M, Mayatepek E, Wagner D, Domann M, Sonntag HG, Bremer HJ(1997). Influence of n-6 and n-3 polyunsaturated fatty acids on the resistance to experimental tuberculosis. Metabolism, 46:619-624
[220] McFarland CT, Fan YY, Chapkin RS, Weeks BR, McMurray DN(2008). Dietary polyunsaturated fatty acids modulate resistance to Mycobacterium tuberculosis in guinea pigs. J Nutr, 138:2123-2128
[221] Jordao L, Lengeling A, Bordat Y, Boudou F, Gicquel B, Neyrolles O, Becker PD, Guzman CA, Griffiths G, Anes E(2008). Effects of omega-3 and -6 fatty acids on Mycobacterium tuberculosis in macrophages and in mice. Microbes Infect, 10:1379-1386
[222] Bonilla DL, Fan YY, Chapkin RS, McMurray DN(2010). Transgenic mice enriched in omega-3 fatty acids are more susceptible to pulmonary tuberculosis: impaired resistance to tuberculosis in fat-1 mice. J Infect Dis, 201:399-408
[223] Fritsche KL, Shahbazian LM, Feng C, Berg JN(1997). Dietary fish oil reduces survival and impairs bacterial clearance in C3H/Hen mice challenged with Listeria monocytogenes. Clin Sci (Lond)92:95-101
[224] Chang HR, Dulloo AG, Vladoianu IR, Piguet PF, Arsenijevic D, Girardier L, Pechere JC(1992). Fish oil decreases natural resistance of mice to infection with Salmonella typhimurium. Metabolism, 41:1-2
[225] McCay CM, Crowell MF, Maynard LA(1935). The effect of retarded growth upon the length of the life span and upon the ultimate body size. J Nutr, 10:63-79
[226] Anderson RM, Shanmuganayagam D, Weindruch R(2009). Caloric restriction and aging: studies in mice and monkeys. Toxicol Pathol, 37:47-51
[227] Fontana L, Partridge L, Longo VD(2010). Extending healthy life span--from yeast to humans. Science, 328:321-326
[228] 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
[229] Chen J, Astle CM, Harrison DE(2003). Hematopoietic senescence is postponed and hematopoietic stem cell function is enhanced by dietary restriction. Exp Hematol, 31:1097-1103
[230] Chen J, Astle CM, Harrison DE(1998). Delayed immune aging in diet-restricted B6CBAT6 F1 mice is associated with preservation of naive T cells. J Gerontol A Biol Sci Med Sci, 53:B330-337discussion B338–339
[231] Walford RL, Liu RK, Gerbase-Delima M, Mathies M, Smith GS(1973). Longterm dietary restriction and immune function in mice: response to sheep red blood cells and to mitogenic agents. Mech Ageing Dev, 2:447-454
[232] Weindruch R, Devens BH, Raff HV, Walford RL(1983). Influence of dietary restriction and aging on natural killer cell activity in mice. J Immunol, 130:993-996
[233] Weindruch R, Gottesman SR, Walford RL(1982). Modification of age-related immune decline in mice dietarily restricted from or after midadulthood. Proc Natl Acad Sci U S A, 79:898-902
[234] Weindruch R, Walford RL(1982). Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence. Science, 215:1415-1418
[235] Spaulding CC, Walford RL, Effros RB(1997). Calorie restriction inhibits the age-related dysregulation of the cytokines TNF-alpha and IL-6 in C3B10RF1 mice. Mech Ageing Dev, 93:87-94
[236] Fernandes G, Friend P, Yunis EJ, Good RA(1978). Influence of dietary restriction on immunologic function and renal disease in (NZB x NZW) F1 mice. Proc Natl Acad Sci U S A, 75:1500-1504
[237] Friend PS, Fernandes G, Good RA, Michael AF, Yunis EJ(1978). Dietary restrictions early and late: effects on the nephropathy of the NZB X NZW mouse. Lab Invest, 38:629-632
[238] Jankovic V, Messaoudi I, Nikolich-Zugich J(2003). Phenotypic and functional T-cell aging in rhesus macaques (Macaca mulatta): differential behavior of CD4 and CD8 subsets. Blood, 102:3244-3251
[239] Messaoudi I, Fischer M, Warner J, Park B, Mattison J, Ingram DK, Totonchy T, Mori M, Nikolich-Zugich J(2008). Optimal window of caloric restriction onset limits its beneficial impact on T-cell senescence in primates. Aging Cell, 7:908-919
[240] Messaoudi I, Warner J, Fischer M, Park B, Hill B, Mattison J, Lane MA, Roth GS, Ingram DK, Picker LJ, Douek DC, Mori M, Nikolich-Zugich J(2006). Delay of T cell senescence by caloric restriction in aged long-lived nonhuman primates. Proc Natl Acad Sci U S A, 103:19448-19453
[241] Nikolich-Zugich J, Messaoudi I(2005). Mice and flies and monkeys too: caloric restriction rejuvenates the aging immune system of non-human primates. Exp Gerontol, 40:884-893
[242] Ahmed T, Das SK, Golden JK, Saltzman E, Roberts SB, Meydani SN(2009). Calorie restriction enhances T-cell-mediated immune response in adult overweight men and women. J Gerontol A Biol Sci Med Sci, 64:1107-1113
[243] Effros RB, Walford RL, Weindruch R, Mitcheltree C(1991). Influences of dietary restriction on immunity to influenza in aged mice. J Gerontol, 46:B142-147
[244] Gardner EM(2005). Caloric restriction decreases survival of aged mice in response to primary influenza infection. J Gerontol A Biol Sci Med Sci, 60:688-694
[245] Ritz BW, Aktan I, Nogusa S, Gardner EM(2008). Energy restriction impairs natural killer cell function and increases the severity of influenza infection in young adult male C57BL/6 mice. J Nutr, 138:2269-2275
[246] Clinthorne JF, Adams DJ, Fenton JI, Ritz BW, Gardner EM(2010). Short-term re-feeding of previously energy-restricted C57BL/6 male mice restores body weight and body fat and attenuates the decline in natural killer cell function after primary influenza infection. J Nutr, 140:1495-1501
[247] Sun D, Muthukumar AR, Lawrence RA, Fernandes G(2001). Effects of calorie restriction on polymicrobial peritonitis induced by cecum ligation and puncture in young C57BL/6 mice. Clin Diagn Lab Immunol, 8:1003-1011
[248] Kristan DM(2007). Chronic calorie restriction increases susceptibility of laboratory mice (Mus musculus) to a primary intestinal parasite infection. Aging Cell, 6:817-825
[249] Han SN, Adolfsson O, Lee CK, Prolla TA, Ordovas J, Meydani SN(2006). Age and vitamin E-induced changes in gene expression profiles of T cells. J Immunol, 177:6052-6061
[250] Ren Z, Pae M, Dao MC, Smith D, Meydani SN, Wu D(2010). Dietary supplementation with tocotrienols enhances immune function in C57BL/6 mice. J Nutr, 140:1335-1341
[251] Lee C-Y, Wan F(2000). Vitamin E supplementation improves cell-mediated immunity and oxidative stress of Asian men and women. J Nutr, 130:2392-2397
[252] Radhakrishnan AK, Lee AL, Wong PF, Kaur J, Aung H, Nesaretnam K(2009). Daily supplementation of tocotrienol-rich fraction or alpha-tocopherol did not induce immunomodulatory changes in healthy human volunteers. Br J Nutr, 101:810-815
[253] Mahalingam D, Radhakrishnan AK, Amom Z, Ibrahim N, Nesaretnam K(2011). Effects of supplementation with tocotrienol-rich fraction on immune response to tetanus toxoid immunization in normal healthy volunteers. Eur J Clin Nutr, 65:63-69
[254] Gay R, Han SN, Marko M, Belisle S, Bronson R, Meydani SN(2004). The effect of vitamin E on secondary bacterial infection after influenza infection in young and old mice. Ann N Y Acad Sci, 1031:418-421
[255] Hemila H, Kaprio J, Albanes D, Heinonen OP, Virtamo J(2002). Vitamin C, vitamin E, and beta-carotene in relation to common cold incidence in male smokers. Epidemiology, 13:32-37
[256] Hemila H(2007). Vitamin E supplementation and respiratory infections in older people. J Am Geriatr Soc, 55:1311-1313author reply 1313–1314
[257] Hemila H, Kaprio J(2008). Vitamin E supplementation may transiently increase tuberculosis risk in males who smoke heavily and have high dietary vitamin C intake. Br J Nutr, 100:896-902
[258] Hemila H, Kaprio J(2008). Vitamin E supplementation and pneumonia risk in males who initiated smoking at an early age: effect modification by body weight and dietary vitamin C. Nutr J, 7:33
[259] Belisle SE, Hamer DH, Leka LS, Dallal GE, Delgado-Lista J, Fine BC, Jacques PF, Ordovas JM, Meydani SN(2010). IL-2 and IL-10 gene polymorphisms are associated with respiratory tract infection and may modulate the effect of vitamin E on lower respiratory tract infections in elderly nursing home residents. Am J Clin Nutr, 92:106-114
[260] Hodkinson CF, Kelly M, Alexander HD, Bradbury I, Robson PJ, Bonham MP, O'Connor JM, Coudray C, Strain JJ, Wallace JM(2007). Effect of zinc supplementation on the immune status of healthy older individuals aged 55–70 years: the ZENITH Study. J Gerontol A Biol Sci Med Sci, 62:598-608
[261] Bose A, Coles CL, Gunavathi, John H, Moses P, Raghupathy P, Kirubakaran C, Black RE, Brooks WA, Santosham M(2006). Efficacy of zinc in the treatment of severe pneumonia in hospitalized children <2 y old. Am J Clin Nutr, 83:1089-1096quiz 1207
[262] Coles CL, Bose A, Moses PD, Mathew L, Agarwal I, Mammen T, Santosham M(2007). Infectious etiology modifies the treatment effect of zinc in severe pneumonia. Am J Clin Nutr, 86:397-403
[263] Lawson L, Thacher TD, Yassin MA, Onuoha NA, Usman A, Emenyonu NE, Shenkin A, Davies PD, Cuevas LE(2010). Randomized controlled trial of zinc and vitamin A as co-adjuvants for the treatment of pulmonary tuberculosis. Trop Med Int Health, 15:1481-1490
[264] Pakasi TA, Karyadi E, Suratih NM, Salean M, Darmawidjaja N, Bor H, van der Velden K, Dolmans WM, van der Meer JW(2010). Zinc and vitamin A supplementation fails to reduce sputum conversion time in severely malnourished pulmonary tuberculosis patients in Indonesia. Nutr J, 9:41
[265] Takamura T, Harama D, Fukumoto S, Nakamura Y, Shimokawa N, Ishimaru K, Ikegami S, Makino S, Kitamura M, Nakao A(2011). Lactobacillus bulgaricus OLL1181 activates the aryl hydrocarbon receptor pathway and inhibits colitis. Immunol Cell Biol
[266] Paineau D, Carcano D, Leyer G, Darquy S, Alyanakian MA, Simoneau G, Bergmann JF, Brassart D, Bornet F, Ouwehand AC(2008). Effects of seven potential probiotic strains on specific immune responses in healthy adults: a double-blind, randomized, controlled trial. FEMS Immunol Med Microbiol, 53:107-113
[267] Ouwehand AC, Bergsma N, Parhiala R, Lahtinen S, Gueimonde M, Finne-Soveri H, Strandberg T, Pitkala K, Salminen S(2008). Bifidobacterium microbiota and parameters of immune function in elderly subjects. FEMS Immunol Med Microbiol, 53:18-25
[268] Ouwehand AC, Tiihonen K, Saarinen M, Putaala H, Rautonen N(2009). Influence of a combination of Lactobacillus acidophilus NCFM and lactitol on healthy elderly: intestinal and immune parameters. Br J Nutr, 101:367-375
[269] Schiffrin EJ, Parlesak A, Bode C, Bode JC, van't Hof MA, Grathwohl D, Guigoz Y(2009). Probiotic yogurt in the elderly with intestinal bacterial overgrowth: endotoxaemia and innate immune functions. Br J Nutr, 101:961-966
[270] Turchet P, Laurenzano M, Auboiron S, Antoine JM(2003). Effect of fermented milk containing the probiotic Lactobacillus casei DN-114001 on winter infections in free-living elderly subjects: a randomised, controlled pilot study. J Nutr Health Aging, 7:75-77
[271] Tubelius P, Stan V, Zachrisson A(2005). Increasing work-place healthiness with the probiotic Lactobacillus reuteri: a randomised, double-blind placebo-controlled study. Environ Health, 4:25
[272] Winkler P, de Vrese M, Laue C, Schrezenmeir J(2005). Effect of a dietary supplement containing probiotic bacteria plus vitamins and minerals on common cold infections and cellular immune parameters. Int J Clin Pharmacol Ther, 43:318-326
[273] Pregliasco F, Anselmi G, Fonte L, Giussani F, Schieppati S, Soletti L(2008). A new chance of preventing winter diseases by the administration of synbiotic formulations. J Clin Gastroenterol, 42(Suppl 3 Pt 2):S224-233
[274] Mukerji SS, Pynnonen MA, Kim HM, Singer A, Tabor M, Terrell JE(2009). Probiotics as adjunctive treatment for chronic rhinosinusitis: a randomized controlled trial. Otolaryngol Head Neck Surg, 140:202-208
[275] Hojsak I, Abdovic S, Szajewska H, Milosevic M, Krznaric Z, Kolacek S(2010). Lactobacillus GG in the prevention of nosocomial gastrointestinal and respiratory tract infections. Pediatrics, 125:e1171-1177
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