Abstract
The etiology of immunosenescence is complex and can impact on both arms of the immune system resulting in poor vaccine responses and increased rates of infection and malignancy in the elderly. Regular physical exercise has been associated with increased immunity and may serve as a simple lifestyle intervention to counteract the deleterious effects of immunosenescence. Some of the positive effects of exercise for older adults include increased responsiveness to vaccines, greater NK cell function, reduced proportions of exhausted/senescent T cells in the periphery, lower frequency of pro-inflammatory monocytes, enhanced function and number of anti-inflammatory Tregs, and longer leukocyte telomere lengths. Collectively, these findings indicate that habitual exercise has immunoregulatory properties and may delay the onset of immunosenescence; however, it remains to be seen if exercise training can also prevent those impaired immune responses that have been associated with immunosenescence. This is because most longitudinal exercise training studies have failed to document the positive effects of exercise on immunity that have been consistently reported in cross-sectional studies. Multiple problems beset existing randomized controlled trials including vast differences in methodology and reliance on otherwise healthy, untrained people as subjects; however, training intervention studies in “unhealthy” people such as cancer survivors, obese individuals, and HIV-positive patients mostly report positive effects of exercise on immunity. Thus, exercise may contribute to the reversal of immunosenescence in those individuals considered to be “at risk.”
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References
Adriaensen W, Derhovanessian E, Vaes B, Van Pottelbergh G, Degryse JM, Pawelec G, Hamprecht K, Theeten H, Mathei C (2015) CD4:8 ratio >5 is associated with a dominant naive T-cell phenotype and impaired physical functioning in CMV-seropositive very elderly people: results from the BELFRAIL study. J Gerontol A Biol Sci Med Sci 70:143–154
Agius E, Lacy KE, Vukmanovic-Stejic M, Jagger AL, Papageorgiou AP, Hall S, Reed JR, Curnow SJ, Fuentes-Duculan J, Buckley CD, Salmon M, Taams LS, Krueger J, Greenwood J, Klein N, Rustin MH, Akbar AN (2009) Decreased TNF-alpha synthesis by macrophages restricts cutaneous immunosurveillance by memory CD4+ T cells during aging. J Exp Med 206:1929–1940
Agrawal A, Gupta S (2011) Impact of aging on dendritic cell functions in humans. Ageing Res Rev 10:336–345
Agrawal A, Agrawal S, Cao JN, Su H, Osann K, Gupta S (2007) Altered innate immune functioning of dendritic cells in elderly humans: a role of phosphoinositide 3-kinase-signaling pathway. J Immunol 178:6912–6922
Agrawal A, Agrawal S, Tay J, Gupta S (2008) Biology of dendritic cells in aging. J Clin Immunol 28:14–20
Agrawal A, Tay J, Ton S, Agrawal S, Gupta S (2009) Increased reactivity of dendritic cells from aged subjects to self-antigen, the human DNA. J Immunol 182:1138–1145
Allavena P, Garlanda C, Borrello MG, Sica A, Mantovani A (2008) Pathways connecting inflammation and cancer. Curr Opin Genet Dev 18:3–10
Almanzar G, Schwaiger S, Jenewein B, Keller M, Herndler-Brandstetter D, Wurzner R, Schonitzer D, Grubeck-Loebenstein B (2005) Long-term cytomegalovirus infection leads to significant changes in the composition of the CD8+ T-cell repertoire, which may be the basis for an imbalance in the cytokine production profile in elderly persons. J Virol 79:3675–3683
Almeida-Oliveira A, Smith-Carvalho M, Porto LC, Cardoso-Oliveira J, Ribeiro Ados S, Falcao RR, Abdelhay E, Bouzas LF, Thuler LC, Ornellas MH, Diamond HR (2011) Age-related changes in natural killer cell receptors from childhood through old age. Hum Immunol 72:319–329
Alvarez-Rodriguez L, Lopez-Hoyos M, Garcia-Unzueta M, Amado JA, Cacho PM, Martinez-Taboada VM (2012) Age and low levels of circulating vitamin D are associated with impaired innate immune function. J Leukoc Biol 91:829–838
Anane LH, Edwards KM, Burns VE, Drayson MT, Riddell NE, van Zanten JJ, Wallace GR, Mills PJ, Bosch JA (2009) Mobilization of gammadelta T lymphocytes in response to psychological stress, exercise, and beta-agonist infusion. Brain Behav Immun 23:823–829
Armstrong L, Medford AR, Hunter KJ, Uppington KM, Millar AB (2004) Differential expression of Toll-like receptor (TLR)-2 and TLR-4 on monocytes in human sepsis. Clin Exp Immunol 136:312–319
Ashcroft GS, Horan MA, Ferguson MW (1998) Aging alters the inflammatory and endothelial cell adhesion molecule profiles during human cutaneous wound healing. Lab Investig 78:47–58
Balducci S, Zanuso S, Nicolucci A, Fernando F, Cavallo S, Cardelli P, Fallucca S, Alessi E, Letizia C, Jimenez A, Fallucca F, Pugliese G (2010) Anti-inflammatory effect of exercise training in subjects with type 2 diabetes and the metabolic syndrome is dependent on exercise modalities and independent of weight loss. Nutr Metab Cardiovasc Dis 20:608–617
Barlow CE, LaMonte MJ, Fitzgerald SJ, Kampert JB, Perrin JL, Blair SN (2006) Cardiorespiratory fitness is an independent predictor of hypertension incidence among initially normotensive healthy women. Am J Epidemiol 163:142–150
Bartholomeu-Neto J, Brito CJ, Nobrega OT, Sousa VC, Oliveira Toledo J, Silva Paula R, Alves DJ, Ferreira AP, Franco Moraes C, Cordova C (2015) Adaptation to resistance training is associated with higher phagocytic (but not oxidative) activity in neutrophils of older women. J Immunol Res 2015:724982
Bartlett DB, Firth CM, Phillips AC, Moss P, Baylis D, Syddall H, Sayer AA, Cooper C, Lord JM (2012) The age-related increase in low-grade systemic inflammation (Inflammaging) is not driven by cytomegalovirus infection. Aging Cell 11:912–915
Bate SL, Dollard SC, Cannon MJ (2010) Cytomegalovirus seroprevalence in the United States: the national health and nutrition examination surveys, 1988-2004. Clin Infect Dis 50:1439–1447
Baylis D, Bartlett DB, Syddall HE, Ntani G, Gale CR, Cooper C, Lord JM, Sayer AA (2013) Immune-endocrine biomarkers as predictors of frailty and mortality: a 10-year longitudinal study in community-dwelling older people. Age (Dordr) 35:963–971
Beiter T, Fragasso A, Hudemann J, Schild M, Steinacker J, Mooren FC, Niess AM (2014) Neutrophils release extracellular DNA traps in response to exercise. J Appl Physiol (1985) 117:325–333
Bektas A, Zhang Y, Lehmann E, Wood WH 3rd, Becker KG, Madara K, Ferrucci L, Sen R (2014) Age-associated changes in basal NF-kappaB function in human CD4+ T lymphocytes via dysregulation of PI3 kinase. Aging (Albany NY) 6:957–974
Belge KU, Dayyani F, Horelt A, Siedlar M, Frankenberger M, Frankenberger B, Espevik T, Ziegler-Heitbrock L (2002) The proinflammatory CD14+CD16+DR++ monocytes are a major source of TNF. J Immunol 168:3536–3542
Bernstein ED, Gardner EM, Abrutyn E, Gross P, Murasko DM (1998) Cytokine production after influenza vaccination in a healthy elderly population. Vaccine 16:1722–1731
Beshgetoor D, Arrues S, McGuire K (2004) Effect of competitive training on T-cell mediated immune function in Master's female athletes. Int J Sports Med 25:553–558
Beziat V, Descours B, Parizot C, Debre P, Vieillard V (2010) NK cell terminal differentiation: correlated stepwise decrease of NKG2A and acquisition of KIRs. PLoS One 5:e11966
Bigley AB, Simpson RJ (2015) NK cells and exercise: implications for cancer immunotherapy and survivorship. Discov Med 19:433–445
Bigley AB, Lowder TW, Spielmann G, Rector JL, Pircher H, Woods JA, Simpson RJ (2012) NK-cells have an impaired response to acute exercise and a lower expression of the inhibitory receptors KLRG1 and CD158a in humans with latent cytomegalovirus infection. Brain Behav Immun 26:177–186
Bigley AB, Spielmann G, LaVoy EC, Simpson RJ (2013) Can exercise-related improvements in immunity influence cancer prevention and prognosis in the elderly? Maturitas 76:51–56
Bigley AB, Rezvani K, Chew C, Sekine T, Pistillo M, Crucian B, Bollard CM, Simpson RJ (2014) Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Brain Behav Immun 39:160–171
Bigley AB, Rezvani K, Pistillo M, Reed J, Agha N, Kunz H, O'Connor DP, Sekine T, Bollard CM, Simpson RJ (2015a) Acute exercise preferentially redeploys NK-cells with a highly-differentiated phenotype and augments cytotoxicity against lymphoma and multiple myeloma target cells. Part II: impact of latent cytomegalovirus infection and catecholamine sensitivity. Brain Behav Immun 49:59–65
Bigley AB, Spielmann G, Agha N, Simpson RJ (2015b) The effects of age and latent cytomegalovirus infection on NK-cell phenotype and exercise responsiveness in man. Oxidative Med Cell Longev 2015:979645
Bigley AB, Rezvani K, Shah N, Sekine T, Balneger N, Pistillo M, Agha N, Kunz H, O'Connor DP, Bollard CM, Simpson RJ (2016a) Latent cytomegalovirus infection enhances anti-tumour cytotoxicity through accumulation of NKG2C+ NK cells in healthy humans. Clin Exp Immunol 185:239–251
Bigley AB, Spielmann G, Agha N, O'Connor DP, Simpson RJ (2016b) Dichotomous effects of latent CMV infection on the phenotype and functional properties of CD8+ T-cells and NK-cells. Cell Immunol 300:26–32
Bishop NC, Hayashida H, Clark M, Coombs C, Miller S, Stensel DJ (2014) Effect of acute and regular exercise on growth hormone secretagogue receptor-1a expression in human lymphocytes, T cell subpopulation and monocytes. Brain Behav Immun 39:172–179
Biswas SK, Mantovani A (2010) Macrophage plasticity and interaction with lymphocyte subsets: cancer as a paradigm. Nat Immunol 11:889–896
Blair SN, Jackson AS (2001) Physical fitness and activity as separate heart disease risk factors: a meta-analysis. Med Sci Sports Exerc 33:762–764
Blair SN, Kampert JB, Kohl HW 3rd, Barlow CE, Macera CA, Paffenbarger RS Jr, Gibbons LW (1996) Influences of cardiorespiratory fitness and other precursors on cardiovascular disease and all-cause mortality in men and women. JAMA 276:205–210
Bliederhaeuser C, Grozdanov V, Speidel A, Zondler L, Ruf WP, Bayer H, Kiechle M, Feiler MS, Freischmidt A, Brenner D, Witting A, Hengerer B, Fandrich M, Ludolph AC, Weishaupt JH, Gillardon F, Danzer KM (2016) Age-dependent defects of alpha-synuclein oligomer uptake in microglia and monocytes. Acta Neuropathol 131:379–391
Born J, Uthgenannt D, Dodt C, Nunninghoff D, Ringvolt E, Wagner T, Fehm HL (1995) Cytokine production and lymphocyte subpopulations in aged humans. An assessment during nocturnal sleep. Mech Ageing Dev 84:113–126
Borrego F, Alonso MC, Galiani MD, Carracedo J, Ramirez R, Ostos B, Pena J, Solana R (1999) NK phenotypic markers and IL2 response in NK cells from elderly people. Exp Gerontol 34:253–265
Brown FF, Bigley AB, Sherry C, Neal CM, Witard OC, Simpson RJ, Galloway SD (2014) Training status and sex influence on senescent T-lymphocyte redistribution in response to acute maximal exercise. Brain Behav Immun 39:152–159
Brown FF, Bigley AB, Ross JC, LaVoy EC, Simpson RJ, Galloway SD (2015) T-lymphocyte populations following a period of high volume training in female soccer players. Physiol Behav 152:175–181
Brunner S, Herndler-Brandstetter D, Weinberger B, Grubeck-Loebenstein B (2011) Persistent viral infections and immune aging. Ageing Res Rev 10:362–369
Bruunsgaard H, Pedersen BK (2000) Special feature for the Olympics: effects of exercise on the immune system: effects of exercise on the immune system in the elderly population. Immunol Cell Biol 78:523–531
Bruunsgaard H, Andersen-Ranberg K, Jeune B, Pedersen AN, Skinhoj P, Pedersen BK (1999) A high plasma concentration of TNF-alpha is associated with dementia in centenarians. J Gerontol A Biol Sci Med Sci 54:M357–M364
Butcher SK, Chahal H, Nayak L, Sinclair A, Henriquez NV, Sapey E, O'Mahony D, Lord JM (2001) Senescence in innate immune responses: reduced neutrophil phagocytic capacity and CD16 expression in elderly humans. J Leukoc Biol 70:881–886
Campbell PT, Wener MH, Sorensen B, Wood B, Chen-Levy Z, Potter JD, McTiernan A, Ulrich CM (2008) Effect of exercise on in vitro immune function: a 12-month randomized, controlled trial among postmenopausal women. J Appl Physiol (1985) 104:1648–1655
Campbell JP, Edwards KM, Ring C, Drayson MT, Bosch JA, Inskip A, Long JE, Pulsford D, Burns VE (2010) The effects of vaccine timing on the efficacy of an acute eccentric exercise intervention on the immune response to an influenza vaccine in young adults. Brain Behav Immun 24:236–242
Carlsten M, Norell H, Bryceson YT, Poschke I, Schedvins K, Ljunggren HG, Kiessling R, Malmberg KJ (2009) Primary human tumor cells expressing CD155 impair tumor targeting by down-regulating DNAM-1 on NK cells. J Immunol 183:4921–4930
Carrega P, Morandi B, Costa R, Frumento G, Forte G, Altavilla G, Ratto GB, Mingari MC, Moretta L, Ferlazzo G (2008) Natural killer cells infiltrating human nonsmall-cell lung cancer are enriched in CD56 bright CD16(−) cells and display an impaired capability to kill tumor cells. Cancer 112:863–875
CDC (2011) Update: influenza activity - United States, 2010–11 season, and composition of the 2011–12 influenza vaccine. MMWR Morb Mortal Rep 60: 7
Cesari M, Penninx BW, Pahor M, Lauretani F, Corsi AM, Rhys Williams G, Guralnik JM, Ferrucci L (2004) Inflammatory markers and physical performance in older persons: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 59:242–248
Chatta GS, Dale DC (1996) Aging and haemopoiesis. Implications for treatment with haemopoietic growth factors. Drugs Aging 9:37–47
Cherkas LF, Hunkin JL, Kato BS, Richards JB, Gardner JP, Surdulescu GL, Kimura M, Lu X, Spector TD, Aviv A (2008) The association between physical activity in leisure time and leukocyte telomere length. Arch Intern Med 168:154–158
Chiang LM, Chen YJ, Chiang J, Lai LY, Chen YY, Liao HF (2007) Modulation of dendritic cells by endurance training. Int J Sports Med 28:798–803
Chidrawar SM, Khan N, Chan YL, Nayak L, Moss PA (2006) Ageing is associated with a decline in peripheral blood CD56bright NK cells. Immun Ageing 3:10
Chiplunkar S, Dhar S, Wesch D, Kabelitz D (2009) Gammadelta T cells in cancer immunotherapy: current status and future prospects. Immunotherapy 1:663–678
Chmielewski PP, Boryslawski K, Chmielowiec K, Chmielowiec J, Strzelec B (2016) The association between total leukocyte count and longevity: evidence from longitudinal and cross-sectional data. Ann Anat 204:1–10
Chubak J, McTiernan A, Sorensen B, Wener MH, Yasui Y, Velasquez M, Wood B, Rajan KB, Wetmore CM, Potter JD, Ulrich CM (2006) Moderate-intensity exercise reduces the incidence of colds among postmenopausal women. Am J Med 119:937–942
Church TS, Earnest CP, Thompson AM, Priest EL, Rodarte RQ, Saunders T, Ross R, Blair SN (2010) Exercise without weight loss does not reduce C-reactive protein: the INFLAME study. Med Sci Sports Exerc 42:708–716
Coca S, Perez-Piqueras J, Martinez D, Colmenarejo A, Saez MA, Vallejo C, Martos JA, Moreno M (1997) The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79:2320–2328
Colbert LH, Visser M, Simonsick EM, Tracy RP, Newman AB, Kritchevsky SB, Pahor M, Taaffe DR, Brach J, Rubin S, Harris TB (2004) Physical activity, exercise, and inflammatory markers in older adults: findings from the Health, Aging and Body Composition Study. J Am Geriatr Soc 52:1098–1104
Cretel E, Veen I, Pierres A, Bongrand P, Gavazzi G (2010) Immunosenescence and infections, myth or reality? Med Mal Infect 40:307–318
Cros J, Cagnard N, Woollard K, Patey N, Zhang SY, Senechal B, Puel A, Biswas SK, Moshous D, Picard C, Jais JP, D'Cruz D, Casanova JL, Trouillet C, Geissmann F (2010) Human CD14dim monocytes patrol and sense nucleic acids and viruses via TLR7 and TLR8 receptors. Immunity 33:375–386
Dalboni TM, Abe AE, de Oliveira CE, Lara VS, Campanelli AP, Gasparoto CT, Gasparoto TH (2013) Activation profile of CXCL8-stimulated neutrophils and aging. Cytokine 61:716–719
Davis JM, Kohut ML, Colbert LH, Jackson DA, Ghaffar A, Mayer EP (1997) Exercise, alveolar macrophage function, and susceptibility to respiratory infection. J Appl Physiol (1985) 83:1461–1466
Davis JM, Murphy EA, Brown AS, Carmichael MD, Ghaffar A, Mayer EP (2004) Effects of moderate exercise and oat beta-glucan on innate immune function and susceptibility to respiratory infection. Am J Physiol Regul Integr Comp Physiol 286:R366–R372
Davison G, Allgrove J, Gleeson M (2009) Salivary antimicrobial peptides (LL-37 and alpha-defensins HNP1-3), antimicrobial and IgA responses to prolonged exercise. Eur J Appl Physiol 106:277–284
De Araujo AL, Rodrigues-Silva LC, Ruiz-Fernandes J, Toledo-Matias MS, Santos-Boas L, Martins-Machado C, Garcez-Leme LE, and Benard G (2015) Elderly men with moderate and intense training lifestyle present sustained higher antibody responses to influenza vaccine. Age (Dordr) 37: 105
de Gonzalo-Calvo D, Fernandez-Garcia B, de Luxan-Delgado B, Rodriguez-Gonzalez S, Garcia-Macia M, Suarez FM, Solano JJ, Rodriguez-Colunga MJ, Coto-Montes A (2012) Long-term training induces a healthy inflammatory and endocrine emergent biomarker profile in elderly men. Age (Dordr) 34:761–771
De Maria A, Moretta L (2011) Revisited function of human NK cell subsets. Cell Cycle 10:1178–1179
De Martinis M, Modesti M, Ginaldi L (2004) Phenotypic and functional changes of circulating monocytes and polymorphonuclear leucocytes from elderly persons. Immunol Cell Biol 82:415–420
de Pablo-Bernal RS, Canizares J, Rosado I, Galva MI, Alvarez-Rios AI, Carrillo-Vico A, Ferrando-Martinez S, Munoz-Fernandez MA, Rafii-El-Idrissi Benhnia M, Pacheco YM, Ramos R, Leal M, Ruiz-Mateos E (2016) Monocyte phenotype and polyfunctionality are associated with elevated soluble inflammatory markers, cytomegalovirus infection, and functional and cognitive decline in elderly adults. J Gerontol A Biol Sci Med Sci 71:610–618
Deckx N, Wens I, Nuyts AH, Hens N, De Winter BY, Koppen G, Goossens H, Van Damme P, Berneman ZN, Eijnde BO, Cools N (2016) 12 weeks of combined endurance and resistance training reduces innate markers of inflammation in a randomized controlled clinical trial in patients with multiple sclerosis. Mediat Inflamm 2016:6789276
DelaRosa O, Pawelec G, Peralbo E, Wikby A, Mariani E, Mocchegiani E, Tarazona R, Solana R (2006) Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology 7:471–481
Della Bella S, Bierti L, Presicce P, Arienti R, Valenti M, Saresella M, Vergani C, Villa ML (2007) Peripheral blood dendritic cells and monocytes are differently regulated in the elderly. Clin Immunol 122:220–228
Dopheide JF, Obst V, Doppler C, Radmacher MC, Scheer M, Radsak MP, Gori T, Warnholtz A, Fottner C, Daiber A, Munzel T, Espinola-Klein C (2012) Phenotypic characterisation of pro-inflammatory monocytes and dendritic cells in peripheral arterial disease. Thromb Haemost 108:1198–1207
Drela N, Kozdron E, Szczypiorski P (2004) Moderate exercise may attenuate some aspects of immunosenescence. BMC Geriatr 4:8
Dunne PJ, Faint JM, Gudgeon NH, Fletcher JM, Plunkett FJ, Soares MV, Hislop AD, Annels NE, Rickinson AB, Salmon M, Akbar AN (2002) Epstein-Barr virus-specific CD8(+) T cells that re-express CD45RA are apoptosis-resistant memory cells that retain replicative potential. Blood 100:933–940
Duzova H, Karakoc Y, Emre MH, Dogan ZY, Kilinc E (2009) Effects of acute moderate and strenuous exercise bouts on IL-17 production and inflammatory response in trained rats. J Sports Sci Med 8:219–224
Edwards KM, Burns VE, Reynolds T, Carroll D, Drayson M, Ring C (2006) Acute stress exposure prior to influenza vaccination enhances antibody response in women. Brain Behav Immun 20:159–168
Edwards KM, Burns VE, Allen LM, McPhee JS, Bosch JA, Carroll D, Drayson M, Ring C (2007) Eccentric exercise as an adjuvant to influenza vaccination in humans. Brain Behav Immun 21:209–217
Elenkov IJ (2004) Glucocorticoids and the Th1/Th2 balance. Ann N Y Acad Sci 1024:138–146
Elosua R, Bartali B, Ordovas JM, Corsi AM, Lauretani F, Ferrucci L, InChianti Investigators (2005) Association between physical activity, physical performance, and inflammatory biomarkers in an elderly population: the InCHIANTI study. J Gerontol A Biol Sci Med Sci 60:760–767
Ershler WB, Sun WH, Binkley N, Gravenstein S, Volk MJ, Kamoske G, Klopp 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 is modifiable by dietary restriction. Lymphokine Cytokine Res 12:225–230
Evenson KR, Stevens J, Cai J, Thomas R, Thomas O (2003) The effect of cardiorespiratory fitness and obesity on cancer mortality in women and men. Med Sci Sports Exerc 35:270–277
Fahlman M, Boardley D, Flynn MG, Braun WA, Lambert CP, Bouillon LE (2000) Effects of endurance training on selected parameters of immune function in elderly women. Gerontology 46:97–104
Fairey AS, Courneya KS, Field CJ, Bell GJ, Jones LW, Mackey JR (2005) Randomized controlled trial of exercise and blood immune function in postmenopausal breast cancer survivors. J Appl Physiol (1985) 98:1534–1540
Farag SS, VanDeusen JB, Fehniger TA, Caligiuri MA (2003) Biology and clinical impact of human natural killer cells. Int J Hematol 78:7–17
Ferguson FG, Wikby A, Maxson P, Olsson J, Johansson B (1995) Immune parameters in a longitudinal study of a very old population of Swedish people: a comparison between survivors and nonsurvivors. J Gerontol A Biol Sci Med Sci 50:B378–B382
Ferlazzo G, Pack M, Thomas D, Paludan C, Schmid D, Strowig T, Bougras G, Muller WA, Moretta L, Munz C (2004) Distinct roles of IL-12 and IL-15 in human natural killer cell activation by dendritic cells from secondary lymphoid organs. Proc Natl Acad Sci U S A 101:16606–16611
Ferrando-Martinez S, Romero-Sanchez MC, Solana R, Delgado J, de la Rosa R, Munoz-Fernandez MA, Ruiz-Mateos E, Leal M (2013) Thymic function failure and C-reactive protein levels are independent predictors of all-cause mortality in healthy elderly humans. Age (Dordr) 35:251–259
Figueroa-Vega N, Moreno-Frias C, Malacara JM (2015) Alterations in adhesion molecules, pro-inflammatory cytokines and cell-derived microparticles contribute to intima-media thickness and symptoms in postmenopausal women. PLoS One 10:e0120990
Fischer CP, Berntsen A, Perstrup LB, Eskildsen P, Pedersen BK (2007) Plasma levels of interleukin-6 and C-reactive protein are associated with physical inactivity independent of obesity. Scand J Med Sci Sports 17:580–587
Flynn MG, Fahlman M, Braun WA, Lambert CP, Bouillon LE, Brolinson PG, Armstrong CW (1999) Effects of resistance training on selected indexes of immune function in elderly women. J Appl Physiol (1985) 86:1905–1913
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
Fortin CF, McDonald PP, Lesur O, Fulop T Jr (2008) Aging and neutrophils: there is still much to do. Rejuvenation Res 11:873–882
Franceschi C, Campisi J (2014) Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci 69(Suppl 1):S4–S9
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
Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panourgia MP, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105
Fulop T Jr, Foris G, Worum I, Leovey A (1985) Age-dependent alterations of fc gamma receptor-mediated effector functions of human polymorphonuclear leucocytes. Clin Exp Immunol 61:425–432
Fulop T Jr, Fouquet C, Allaire P, Perrin N, Lacombe G, Stankova J, Rola-Pleszczynski M, Gagne D, Wagner JR, Khalil A, Dupuis G (1997) Changes in apoptosis of human polymorphonuclear granulocytes with aging. Mech Ageing Dev 96:15–34
Gano LB, Donato AJ, Pierce GL, Pasha HM, Magerko KA, Roeca C, Seals DR (2011) Increased proinflammatory and oxidant gene expression in circulating mononuclear cells in older adults: amelioration by habitual exercise. Physiol Genomics 43:895–902
Gatmaitan BG, Chason JL, Lerner AM (1970) Augmentation of the virulence of murine coxsackie-virus B-3 myocardiopathy by exercise. J Exp Med 131:1121–1136
Gayoso I, Sanchez-Correa B, Campos C, Alonso C, Pera A, Casado JG, Morgado S, Tarazona R, Solana R (2011) Immunosenescence of human natural killer cells. J Innate Immun 3:337–343
Ge Q, Bai A, Jones B, Eisen HN, Chen J (2004) Competition for self-peptide-MHC complexes and cytokines between naive and memory CD8+ T cells expressing the same or different T cell receptors. Proc Natl Acad Sci U S A 101:3041–3046
Geissmann F, Gordon S, Hume DA, Mowat AM, Randolph GJ (2010) Unravelling mononuclear phagocyte heterogeneity. Nat Rev Immunol 10:453–460
Giunta B, Fernandez F, Nikolic WV, Obregon D, Rrapo E, Town T, Tan J (2008) Inflammaging as a prodrome to Alzheimer's disease. J Neuroinflammation 5:51
Gleeson M, McDonald WA, Pyne DB, Cripps AW, Francis JL, Fricker PA, Clancy RL (1999) Salivary IgA levels and infection risk in elite swimmers. Med Sci Sports Exerc 31:67–73
Gleeson M, Bishop N, Oliveira M, McCauley T, Tauler P, Muhamad AS (2012) Respiratory infection risk in athletes: association with antigen-stimulated IL-10 production and salivary IgA secretion. Scand J Med Sci Sports 22:410–417
Gomez CR, Nomellini V, Faunce DE, Kovacs EJ (2008) Innate immunity and aging. Exp Gerontol 43:718–728
Goodwin K, Viboud C, Simonsen L (2006) Antibody response to influenza vaccination in the elderly: a quantitative review. Vaccine 24:1159–1169
Grant RW, Mariani RA, Vieira VJ, Fleshner M, Smith TP, Keylock KT, Lowder TW, McAuley E, Hu L, Chapman-Novakofski K, Woods JA (2008) Cardiovascular exercise intervention improves the primary antibody response to keyhole limpet hemocyanin (KLH) in previously sedentary older adults. Brain Behav Immun 22:923–932
Griffiths SJ, Riddell NE, Masters J, Libri V, Henson SM, Wertheimer A, Wallace D, Sims S, Rivino L, Larbi A, Kemeny DM, Nikolich-Zugich J, Kern F, Klenerman P, Emery VC, Akbar AN (2013) Age-associated increase of low-avidity cytomegalovirus-specific CD8+ T cells that re-express CD45RA. J Immunol 190:5363–5372
Grubeck-Loebenstein B, Della Bella S, Iorio AM, Michel JP, Pawelec G, Solana R (2009) Immunosenescence and vaccine failure in the elderly. Aging Clin Exp Res 21:201–209
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. Mech Ageing Dev 93:215–222
Guichard C, Pedruzzi E, Dewas C, Fay M, Pouzet C, Bens M, Vandewalle A, Ogier-Denis E, Gougerot-Pocidalo MA, Elbim C (2005) Interleukin-8-induced priming of neutrophil oxidative burst requires sequential recruitment of NADPH oxidase components into lipid rafts. J Biol Chem 280:37021–37032
Gulubova M, Manolova I, Kyurkchiev D, Julianov A, Altunkova I (2009) Decrease in intrahepatic CD56+ lymphocytes in gastric and colorectal cancer patients with liver metastases. APMIS 117:870–879
Haaland DA, Sabljic TF, Baribeau DA, Mukovozov IM, Hart LE (2008) Is regular exercise a friend or foe of the aging immune system? A systematic review. Clin J Sport Med 18:539–548
Hannoun C, Megas F, Piercy J (2004) Immunogenicity and protective efficacy of influenza vaccination. Virus Res 103:133–138
Hayhoe RP, Henson SM, Akbar AN, Palmer DB (2010) Variation of human natural killer cell phenotypes with age: identification of a unique KLRG1-negative subset. Hum Immunol 71:676–681
Hazeldine J, Lord JM (2013) The impact of ageing on natural killer cell function and potential consequences for health in older adults. Ageing Res Rev 12:1069–1078
Hazeldine J, Hampson P, Lord JM (2012) Reduced release and binding of perforin at the immunological synapse underlies the age-related decline in natural killer cell cytotoxicity. Aging Cell 11:751–759
Hazeldine J, Harris P, Chapple IL, Grant M, Greenwood H, Livesey A, Sapey E, Lord JM (2014) Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals. Aging Cell 13:690–698
Heron M, Tejada-Vera B (2009) Deaths: leading causes for 2005. Natl Vital Stat Rep 58:1–97
Ho CS, Lopez JA, Vuckovic S, Pyke CM, Hockey RL, Hart DN (2001) Surgical and physical stress increases circulating blood dendritic cell counts independently of monocyte counts. Blood 98:140–145
Hoffman-Goetz L, Quadrilatero J (2003) Treadmill exercise in mice increases intestinal lymphocyte loss via apoptosis. Acta Physiol Scand 179:289–297
Hojman P, Dethlefsen C, Brandt C, Hansen J, Pedersen L, Pedersen BK (2011) Exercise-induced muscle-derived cytokines inhibit mammary cancer cell growth. Am J Physiol Endocrinol Metab 301:E504–E510
Hume DA, Ross IL, Himes SR, Sasmono RT, Wells CA, Ravasi T (2002) The mononuclear phagocyte system revisited. J Leukoc Biol 72:621–627
Hwang KA, Kim HR, Kang I (2009) Aging and human CD4(+) regulatory T cells. Mech Ageing Dev 130:509–517
Iancu EM, Corthesy P, Baumgaertner P, Devevre E, Voelter V, Romero P, Speiser DE, Rufer N (2009) Clonotype selection and composition of human CD8 T cells specific for persistent herpes viruses varies with differentiation but is stable over time. J Immunol 183:319–331
Ilback NG, Fohlman J, Friman G (1989) Exercise in coxsackie B3 myocarditis: effects on heart lymphocyte subpopulations and the inflammatory reaction. Am Heart J 117:1298–1302
Imai K, Matsuyama S, Miyake S, Suga K, Nakachi K (2000) Natural cytotoxic activity of peripheral-blood lymphocytes and cancer incidence: an 11-year follow-up study of a general population. Lancet 356:1795–1799
Ishigami S, Natsugoe S, Tokuda K, Nakajo A, Che X, Iwashige H, Aridome K, Hokita S, Aikou T (2000) Prognostic value of intratumoral natural killer cells in gastric carcinoma. Cancer 88:577–583
Jahn J, Spielau M, Brandsch C, Stangl GI, Delank KS, Bahr I, Berreis T, Wrann CD, Kielstein H (2015) Decreased NK cell functions in obesity can be reactivated by fat mass reduction. Obesity (Silver Spring) 23:2233–2241
Janssens JP, Krause KH (2004) Pneumonia in the very old. Lancet Infect Dis 4:112–124
Jing Y, Shaheen E, Drake RR, Chen N, Gravenstein S, Deng Y (2009) Aging is associated with a numerical and functional decline in plasmacytoid dendritic cells, whereas myeloid dendritic cells are relatively unaltered in human peripheral blood. Hum Immunol 70:777–784
Jylha M, Paavilainen P, Lehtimaki T, Goebeler S, Karhunen PJ, Hervonen A, Hurme M (2007) Interleukin-1 receptor antagonist, interleukin-6, and C-reactive protein as predictors of mortality in nonagenarians: the vitality 90+ study. J Gerontol A Biol Sci Med Sci 62:1016–1021
Kadoglou NP, Iliadis F, Angelopoulou N, Perrea D, Ampatzidis G, Liapis CD, Alevizos M (2007a) The anti-inflammatory effects of exercise training in patients with type 2 diabetes mellitus. Eur J Cardiovasc Prev Rehabil 14:837–843
Kadoglou NP, Perrea D, Iliadis F, Angelopoulou N, Liapis C, Alevizos M (2007b) Exercise reduces resistin and inflammatory cytokines in patients with type 2 diabetes. Diabetes Care 30:719–721
Kapasi ZF, Catlin PA, Joyner DR, Lewis ML, Schwartz AL, Townsend EL (2000) The effects of intense physical exercise on secondary antibody response in young and old mice. Phys Ther 80:1076–1086
Kapasi ZF, Ouslander JG, Schnelle JF, Kutner M, Fahey JL (2003) Effects of an exercise intervention on immunologic parameters in frail elderly nursing home residents. J Gerontol A Biol Sci Med Sci 58:636–643
Kapasi ZF, McRae ML, Ahmed R (2005) Suppression of viral specific primary T-cell response following intense physical exercise in young but not old mice. J Appl Physiol (1985) 98:663–671
Kawai T, Akira S (2007) Signaling to NF-kappaB by toll-like receptors. Trends Mol Med 13:460–469
Kawanishi N, Yano H, Yokogawa Y, Suzuki K (2010) Exercise training inhibits inflammation in adipose tissue via both suppression of macrophage infiltration and acceleration of phenotypic switching from M1 to M2 macrophages in high-fat-diet-induced obese mice. Exerc Immunol Rev 16:105–118
Kelsey CR, Scott JM, Lane A, Schwitzer E, West MJ, Thomas S, Hendon JE 2nd, Michalski MG, Horwitz ME, Hennig T, and Jones LW (2014). Cardiopulmonary exercise testing prior to myeloablative allo-SCT: a feasibility study. Bone Marrow Transplant 49: 1330–1336.
Keylock KT, Lowder T, Leifheit KA, Cook M, Mariani RA, Ross K, Kim K, Chapman-Novakofski K, McAuley E, Woods JA (2007) Higher antibody, but not cell-mediated, responses to vaccination in high physically fit elderly. J Appl Physiol (1985) 102:1090–1098
Koch S, Larbi A, Ozcelik D, Solana R, Gouttefangeas C, Attig S, Wikby A, Strindhall J, Franceschi C, Pawelec G (2007) Cytomegalovirus infection: a driving force in human T cell immunosenescence. Ann N Y Acad Sci 1114:23–35
Kodama S, Shu M, Saito K, Murakami H, Tanaka K, Kuno S, Ajisaka R, Sone Y, Onitake F, Takahashi A, Shimano H, Kondo K, Yamada N, Sone H (2007) Even low-intensity and low-volume exercise training may improve insulin resistance in the elderly. Intern Med 46:1071–1077
Kodama S, Saito K, Tanaka S, Maki M, Yachi Y, Asumi M, Sugawara A, Totsuka K, Shimano H, Ohashi Y, Yamada N, Sone H (2009) Cardiorespiratory fitness as a quantitative predictor of all-cause mortality and cardiovascular events in healthy men and women: a meta-analysis. JAMA 301:2024–2035
Kohut ML, Boehm GW, Moynihan JA (2001) Moderate exercise is associated with enhanced antigen-specific cytokine, but not IgM antibody production in aged mice. Mech Ageing Dev 122:1135–1150
Kohut ML, Arntson BA, Lee W, Rozeboom K, Yoon KJ, Cunnick JE, McElhaney J (2004) Moderate exercise improves antibody response to influenza immunization in older adults. Vaccine 22:2298–2306
Kohut ML, McCann DA, Russell DW, Konopka DN, Cunnick JE, Franke WD, Castillo MC, Reighard AE, Vanderah E (2006) Aerobic exercise, but not flexibility/resistance exercise, reduces serum IL-18, CRP, and IL-6 independent of beta-blockers, BMI, and psychosocial factors in older adults. Brain Behav Immun 20:201–209
Konjevic G, Mirjacic Martinovic K, Jurisic V, Babovic N, Spuzic I (2009) Biomarkers of suppressed natural killer (NK) cell function in metastatic melanoma: decreased NKG2D and increased CD158a receptors on CD3-CD16+ NK cells. Biomarkers 14:258–270
Kovalenko EI, Boyko AA, Semenkov VF, Lutsenko GV, Grechikhina MV, Kanevskiy LM, Azhikina TL, Telford WG, Sapozhnikov AM (2014) ROS production, intracellular HSP70 levels and their relationship in human neutrophils: effects of age. Oncotarget 5:11800–11812
Krishnaraj R, Bhooma T (1996) Cytokine sensitivity of human NK cells during immunosenescence. 2. IL2-induced interferon gamma secretion. Immunol Lett 50:59–63
Kruger K, Lechtermann A, Fobker M, Volker K, Mooren FC (2008) Exercise-induced redistribution of T lymphocytes is regulated by adrenergic mechanisms. Brain Behav Immun 22:324–338
Kullo IJ, Khaleghi M, Hensrud DD (2007) Markers of inflammation are inversely associated with VO2 max in asymptomatic men. J Appl Physiol (1985) 102:1374–1379
Kumar V, Sharma A (2010) Neutrophils: Cinderella of innate immune system. Int Immunopharmacol 10:1325–1334
Kunz H, Bishop NC, Spielmann G, Pistillo M, Reed J, Ograjsek T, Park Y, Mehta SK, Pierson DL, Simpson RJ (2015) Fitness level impacts salivary antimicrobial protein responses to a single bout of cycling exercise. Eur J Appl Physiol 115:1015–1027
Lancaster GI, Khan Q, Drysdale P, Wallace F, Jeukendrup AE, Drayson MT, Gleeson M (2005) The physiological regulation of toll-like receptor expression and function in humans. J Physiol 563:945–955
Lande R, Gilliet M (2010) Plasmacytoid dendritic cells: key players in the initiation and regulation of immune responses. Ann N Y Acad Sci 1183:89–103
Lanzavecchia A, Sallusto F (2001) Regulation of T cell immunity by dendritic cells. Cell 106:263–266
Larbi A, Douziech N, Fortin C, Linteau A, Dupuis G, Fulop T Jr (2005) The role of the MAPK pathway alterations in GM-CSF modulated human neutrophil apoptosis with aging. Immun Ageing 2:6
Lautenbach A, Wrann CD, Jacobs R, Muller G, Brabant G, Nave H (2009) Altered phenotype of NK cells from obese rats can be normalized by transfer into lean animals. Obesity (Silver Spring) 17:1848–1855
LaVoy EC, Bollard CM, Hanley PJ, O'Connor DP, Lowder TW, Bosch JA, Simpson RJ (2015) A single bout of dynamic exercise by healthy adults enhances the generation of monocyte-derived-dendritic cells. Cell Immunol 295:52–59
Le Garff-Tavernier M, Beziat V, Decocq J, Siguret V, Gandjbakhch F, Pautas E, Debre P, Merle-Beral H, Vieillard V (2010) Human NK cells display major phenotypic and functional changes over the life span. Aging Cell 9:527–535
Levy SM, Herberman RB, Lee J, Whiteside T, Beadle M, Heiden L, Simons A (1991) Persistently low natural killer cell activity, age, and environmental stress as predictors of infectious morbidity. Nat Immun Cell Growth Regul 10:289–307
Li H, Weng P, Najarro K, Xue QL, Semba RD, Margolick JB, Leng SX (2014) Chronic CMV infection in older women: longitudinal comparisons of CMV DNA in peripheral monocytes, anti-CMV IgG titers, serum IL-6 levels, and CMV pp65 (NLV)-specific CD8(+) T-cell frequencies with twelve year follow-up. Exp Gerontol 54:84–89
Libby P (2006) Inflammation and cardiovascular disease mechanisms. Am J Clin Nutr 83:456S–460S
Lio D, Scola L, Crivello A, Colonna-Romano G, Candore G, Bonafe M, Cavallone L, Franceschi C, Caruso C (2002) Gender-specific association between −1082 IL-10 promoter polymorphism and longevity. Genes Immun 3:30–33
Liu J (2012) Effect of Tai Chi exercise on immune function in middle-aged and elderly women. J Sports Med Doping Stud 2:119
Lo Monaco E, Tremante E, Cerboni C, Melucci E, Sibilio L, Zingoni A, Nicotra MR, Natali PG, Giacomini P (2011) Human leukocyte antigen E contributes to protect tumor cells from lysis by natural killer cells. Neoplasia 13:822–830
Lopez-Verges S, Milush JM, Pandey S, York VA, Arakawa-Hoyt J, Pircher H, Norris PJ, Nixon DF, Lanier LL (2010) CD57 defines a functionally distinct population of mature NK cells in the human CD56dimCD16+ NK-cell subset. Blood 116:3865–3874
Lowder T, Padgett DA, Woods JA (2005) Moderate exercise protects mice from death due to influenza virus. Brain Behav Immun 19:377–380
Lowder T, Padgett DA, Woods JA (2006) Moderate exercise early after influenza virus infection reduces the Th1 inflammatory response in lungs of mice. Exerc Immunol Rev 12:97–111
Lowder T, Dugger K, Deshane J, Estell K, Schwiebert LM (2010) Repeated bouts of aerobic exercise enhance regulatory T cell responses in a murine asthma model. Brain Behav Immun 24:153–159
Ludlow AT, Zimmerman JB, Witkowski S, Hearn JW, Hatfield BD, Roth SM (2008) Relationship between physical activity level, telomere length, and telomerase activity. Med Sci Sports Exerc 40:1764–1771
Lutz CT, Moore MB, Bradley S, Shelton BJ, Lutgendorf SK (2005) Reciprocal age related change in natural killer cell receptors for MHC class I. Mech Ageing Dev 126:722–731
Lynch J, Helmrich SP, Lakka TA, Kaplan GA, Cohen RD, Salonen R, Salonen JT (1996) Moderately intense physical activities and high levels of cardiorespiratory fitness reduce the risk of non-insulin-dependent diabetes mellitus in middle-aged men. Arch Intern Med 156:1307–1314
Malm C (2004) Exercise immunology: the current state of man and mouse. Sports Med 34:555–566
Mantovani A, Pierotti MA (2008) Cancer and inflammation: a complex relationship. Cancer Lett 267:180–181
Mariani E, Monaco MC, Cattini L, Sinoppi M, Facchini A (1994) Distribution and lytic activity of NK cell subsets in the elderly. Mech Ageing Dev 76:177–187
Mariani E, Meneghetti A, Neri S, Ravaglia G, Forti P, Cattini L, Facchini A (2002) Chemokine production by natural killer cells from nonagenarians. Eur J Immunol 32:1524–1529
Markofski MM, Flynn MG, Carrillo AE, Armstrong CL, Campbell WW, Sedlock DA (2014) Resistance exercise training-induced decrease in circulating inflammatory CD14+CD16+ monocyte percentage without weight loss in older adults. Eur J Appl Physiol 114:1737–1748
Martin SA, Pence BD, Woods JA (2009) Exercise and respiratory tract viral infections. Exerc Sport Sci Rev 37:157–164
Martinez de Toda I, Mate I, Vida C, Cruces J, De la Fuente M (2016) Immune function parameters as markers of biological age and predictors of longevity. Aging (Albany NY) 8:3110–3119
McElhaney JE, Zhou X, Talbot HK, Soethout E, Bleackley RC, Granville DJ, Pawelec G (2012) The unmet need in the elderly: how immunosenescence, CMV infection, co-morbidities and frailty are a challenge for the development of more effective influenza vaccines. Vaccine 30:2060–2067
McFarlin BK, Flynn MG, Campbell WW, Stewart LK, Timmerman KL (2004) TLR4 is lower in resistance-trained older women and related to inflammatory cytokines. Med Sci Sports Exerc 36:1876–1883
McFarlin BK, Flynn MG, Phillips MD, Stewart LK, Timmerman KL (2005) Chronic resistance exercise training improves natural killer cell activity in older women. J Gerontol A Biol Sci Med Sci 60:1315–1318
McFarlin BK, Flynn MG, Campbell WW, Craig BA, Robinson JP, Stewart LK, Timmerman KL, Coen PM (2006) Physical activity status, but not age, influences inflammatory biomarkers and toll-like receptor 4. J Gerontol A Biol Sci Med Sci 61:388–393
Mege JL, Mehraj V, Capo C (2011) Macrophage polarization and bacterial infections. Curr Opin Infect Dis 24:230–234
Merino A, Buendia P, Martin-Malo A, Aljama P, Ramirez R, Carracedo J (2011) Senescent CD14+CD16+ monocytes exhibit proinflammatory and proatherosclerotic activity. J Immunol 186:1809–1815
Metcalf TU, Cubas RA, Ghneim K, Cartwright MJ, Grevenynghe JV, Richner JM, Olagnier DP, Wilkinson PA, Cameron MJ, Park BS, Hiscott JB, Diamond MS, Wertheimer AM, Nikolich-Zugich J, Haddad EK (2015) Global analyses revealed age-related alterations in innate immune responses after stimulation of pathogen recognition receptors. Aging Cell 14:421–432
Meyerhardt JA, Heseltine D, Niedzwiecki D, Hollis D, Saltz LB, Mayer RJ, Thomas J, Nelson H, Whittom R, Hantel A, Schilsky RL, Fuchs CS (2006) Impact of physical activity on cancer recurrence and survival in patients with stage III colon cancer: findings from CALGB 89803. J Clin Oncol 24:3535–3541
Michishita R, Shono N, Inoue T, Tsuruta T, Node K (2008) Associations of monocytes, neutrophil count, and C-reactive protein with maximal oxygen uptake in overweight women. J Cardiol 52:247–253
Mohamady TM, Borhan WH, Abdallah W, AbdelGhani S (2013) Effect of selected exercise program on natural killer cytotoxic cells activity of post-mastectomy patients. Beni-Suef Univ J Basic Appl Sci 2:114–119
Mohamady HM, Elsisi HF, Aneis YM (2017) Impact of moderate intensity aerobic exercise on chemotherapy-induced anemia in elderly women with breast cancer: a randomized controlled clinical trial. J Adv Res 8:7–12
Mohanty S, Joshi SR, Ueda I, Wilson J, Blevins TP, Siconolfi B, Meng H, Devine L, Raddassi K, Tsang S, Belshe RB, Hafler DA, Kaech SM, Kleinstein SH, Trentalange M, Allore HG, Shaw AC (2015) Prolonged proinflammatory cytokine production in monocytes modulated by interleukin 10 after influenza vaccination in older adults. J Infect Dis 211:1174–1184
Mooren FC, Kruger K (2015) Apoptotic lymphocytes induce progenitor cell mobilization after exercise. J Appl Physiol (1985) 119:135–139
Mooren FC, Bloming D, Lechtermann A, Lerch MM, Volker K (2002) Lymphocyte apoptosis after exhaustive and moderate exercise. J Appl Physiol (1985) 93:147–153
Mooren FC, Volker K, Klocke R, Nikol S, Waltenberger J, Kruger K (2012) Exercise delays neutrophil apoptosis by a G-CSF-dependent mechanism. J Appl Physiol (1985) 113:1082–1090
Moro-Garcia MA, Fernandez-Garcia B, Echeverria A, Rodriguez-Alonso M, Suarez-Garcia FM, Solano-Jaurrieta JJ, Lopez-Larrea C, and Alonso-Arias R (2014) Frequent participation in high volume exercise throughout life is associated with a more differentiated adaptive immune response. Brain Behav Immune 39: 61–74
Moulin CM, Marguti I, Peron JP, Halpern A, Rizzo LV (2011) Bariatric surgery reverses natural killer (NK) cell activity and NK-related cytokine synthesis impairment induced by morbid obesity. Obes Surg 21:112–118
Na YM, Kim MY, Kim YK, Ha YR, Yoon DS (2000) Exercise therapy effect on natural killer cell cytotoxic activity in stomach cancer patients after curative surgery. Arch Phys Med Rehabil 81:777–779
Nave H, Mueller G, Siegmund B, Jacobs R, Stroh T, Schueler U, Hopfe M, Behrendt P, Buchenauer T, Pabst R, Brabant G (2008) Resistance of Janus kinase-2 dependent leptin signaling in natural killer (NK) cells: a novel mechanism of NK cell dysfunction in diet-induced obesity. Endocrinology 149:3370–3378
Nickel T, Emslander I, Sisic Z, David R, Schmaderer C, Marx N, Schmidt-Trucksass A, Hoster E, Halle M, Weis M, Hanssen H (2012) Modulation of dendritic cells and toll-like receptors by marathon running. Eur J Appl Physiol 112:1699–1708
Nicklas BJ, Hsu FC, Brinkley TJ, Church T, Goodpaster BH, Kritchevsky SB, Pahor M (2008) Exercise training and plasma C-reactive protein and interleukin-6 in elderly people. J Am Geriatr Soc 56:2045–2052
Nieman DC (1997a) Immune response to heavy exertion. J Appl Physiol (1985) 82:1385–1394
Nieman DC (1997b) Risk of upper respiratory tract infection in athletes: an epidemiologic and immunologic perspective. J Athl Train 32:344–349
Nieman DC, Nehlsen-Cannarella SL, Markoff PA, Balk-Lamberton AJ, Yang H, Chritton DB, Lee JW, Arabatzis K (1990) The effects of moderate exercise training on natural killer cells and acute upper respiratory tract infections. Int J Sports Med 11:467–473
Nieman DC, Henson DA, Gusewitch G, Warren BJ, Dotson RC, Butterworth DE, Nehlsen-Cannarella SL (1993) Physical activity and immune function in elderly women. Med Sci Sports Exerc 25:823–831
Nieman DC, Cook VD, Henson DA, Suttles J, Rejeski WJ, Ribisl PM, Fagoaga OR, Nehlsen-Cannarella SL (1995a) Moderate exercise training and natural killer cell cytotoxic activity in breast cancer patients. Int J Sports Med 16:334–337
Nieman DC, Henson DA, Sampson CS, Herring JL, Suttles J, Conley M, Stone MH, Butterworth DE, Davis JM (1995b) The acute immune response to exhaustive resistance exercise. Int J Sports Med 16:322–328
Nieman DC, Dumke CI, Henson DA, McAnulty SR, McAnulty LS, Lind RH, Morrow JD (2003) Immune and oxidative changes during and following the Western States Endurance Run. Int J Sports Med 24:541–547
Nieto-Vazquez I, Fernandez-Veledo S, Kramer DK, Vila-Bedmar R, Garcia-Guerra L, Lorenzo M (2008) Insulin resistance associated to obesity: the link TNF-alpha. Arch Physiol Biochem 114:183–194
Nyugen J, Agrawal S, Gollapudi S, Gupta S (2010) Impaired functions of peripheral blood monocyte subpopulations in aged humans. J Clin Immunol 30:806–813
Ogata K, Yokose N, Tamura H, An E, Nakamura K, Dan K, Nomura T (1997) Natural killer cells in the late decades of human life. Clin Immunol Immunopathol 84:269–275
Ogata K, An E, Shioi Y, Nakamura K, Luo S, Yokose N, Minami S, Dan K (2001) Association between natural killer cell activity and infection in immunologically normal elderly people. Clin Exp Immunol 124:392–397
Ogawa K, Oka J, Yamakawa J, Higuchi M (2003) Habitual exercise did not affect the balance of type 1 and type 2 cytokines in elderly people. Mech Ageing Dev 124:951–956
Okutsu M, Yoshida Y, Zhang X, Tamagawa A, Ohkubo T, Tsuji I, Nagatomi R (2008) Exercise training enhances in vivo tuberculosis purified protein derivative response in the elderly. J Appl Physiol (1985) 104:1690–1696
Ostrowski K, Rohde T, Asp S, Schjerling P, Pedersen BK (1999) Pro- and anti-inflammatory cytokine balance in strenuous exercise in humans. J Physiol 515(Pt 1):287–291
Padgett DA, Sheridan JF, Dorne J, Berntson GG, Candelora J, Glaser R (1998) Social stress and the reactivation of latent herpes simplex virus type 1. Proc Natl Acad Sci U S A 95:7231–7235
Panda A, Qian F, Mohanty S, van Duin D, Newman FK, Zhang L, Chen S, Towle V, Belshe RB, Fikrig E, Allore HG, Montgomery RR, Shaw AC (2010) Age-associated decrease in TLR function in primary human dendritic cells predicts influenza vaccine response. J Immunol 184:2518–2527
Pascoe AR, Fiatarone Singh MA, Edwards KM (2014) The effects of exercise on vaccination responses: a review of chronic and acute exercise interventions in humans. Brain Behav Immun 39:33–41
Passlick B, Flieger D, Ziegler-Heitbrock HW (1989) Identification and characterization of a novel monocyte subpopulation in human peripheral blood. Blood 74:2527–2534
Pawelec G, Derhovanessian E, Larbi A, Strindhall J, Wikby A (2009) Cytomegalovirus and human immunosenescence. Rev Med Virol 19:47–56
Pawelec G, Akbar A, Beverley P, Caruso C, Derhovanessian E, Fulop T, Griffiths P, Grubeck-Loebenstein B, Hamprecht K, Jahn G, Kern F, Koch SD, Larbi A, Maier AB, Macallan D, Moss P, Samson S, Strindhall J, Trannoy E, Wills M (2010) Immunosenescence and Cytomegalovirus: where do we stand after a decade? Immun Ageing 7:13
Pedersen BK, Bruunsgaard H (2003) Possible beneficial role of exercise in modulating low-grade inflammation in the elderly. Scand J Med Sci Sports 13:56–62
Pedersen BK, Steensberg A, Schjerling P (2001) Muscle-derived interleukin-6: possible biological effects. J Physiol 536:329–337
Pedersen M, Bruunsgaard H, Weis N, Hendel HW, Andreassen BU, Eldrup E, Dela F, Pedersen BK (2003) Circulating levels of TNF-alpha and IL-6-relation to truncal fat mass and muscle mass in healthy elderly individuals and in patients with type-2 diabetes. Mech Ageing Dev 124:495–502
Pedersen L, Idorn M, Olofsson GH, Lauenborg B, Nookaew I, Hansen RH, Johannesen HH, Becker JC, Pedersen KS, Dethlefsen C, Nielsen J, Gehl J, Pedersen BK, Thor Straten P, Hojman P (2016) Voluntary running suppresses tumor growth through epinephrine- and IL-6-dependent NK cell mobilization and redistribution. Cell Metab 23:554–562
Perna FM, LaPerriere A, Klimas N, Ironson G, Perry A, Pavone J, Goldstein A, Majors P, Makemson D, Talutto C, Schneiderman N, Fletcher MA, Meijer OG, Koppes L (1999) Cardiopulmonary and CD4 cell changes in response to exercise training in early symptomatic HIV infection. Med Sci Sports Exerc 31:973–979
Perry C, Pick M, Bdolach N, Hazan-Halevi I, Kay S, Berr I, Reches A, Harishanu Y, Grisaru D (2013) Endurance exercise diverts the balance between Th17 cells and regulatory T cells. PLoS One 8:e74722
Peters EM, Bateman ED (1983) Ultramarathon running and upper respiratory tract infections. An epidemiological survey. S Afr Med J 64:582–584
Peters T, Weiss JM, Sindrilaru A, Wang H, Oreshkova T, Wlaschek M, Maity P, Reimann J, Scharffetter-Kochanek K (2009) Reactive oxygen intermediate-induced pathomechanisms contribute to immunosenescence, chronic inflammation and autoimmunity. Mech Ageing Dev 130:564–587
Petersen AM, Pedersen BK (2005) The anti-inflammatory effect of exercise. J Appl Physiol (1985) 98:1154–1162
Phillips MD, Flynn MG, McFarlin BK, Stewart LK, Timmerman KL (2010) Resistance training at eight-repetition maximum reduces the inflammatory milieu in elderly women. Med Sci Sports Exerc 42:314–325
Pistillo M, Bigley AB, Spielmann G, LaVoy EC, Morrison MR, Kunz H, Simpson RJ (2013) The effects of age and viral serology on gammadelta T-cell numbers and exercise responsiveness in humans. Cell Immunol 284:91–97
Plackett TP, Boehmer ED, Faunce DE, Kovacs EJ (2004) Aging and innate immune cells. J Leukoc Biol 76:291–299
Plowden J, Renshaw-Hoelscher M, Gangappa S, Engleman C, Katz JM, Sambhara S (2004) Impaired antigen-induced CD8+ T cell clonal expansion in aging is due to defects in antigen presenting cell function. Cell Immunol 229:86–92
Przybyla B, Gurley C, Harvey JF, Bearden E, Kortebein P, Evans WJ, Sullivan DH, Peterson CA, Dennis RA (2006) Aging alters macrophage properties in human skeletal muscle both at rest and in response to acute resistance exercise. Exp Gerontol 41:320–327
Puchta A, Naidoo A, Verschoor CP, Loukov D, Thevaranjan N, Mandur TS, Nguyen PS, Jordana M, Loeb M, Xing Z, Kobzik L, Larche MJ, Bowdish DM (2016) TNF drives monocyte dysfunction with age and results in impaired anti-pneumococcal immunity. PLoS Pathog 12:e1005368
Radom-Aizik S, Zaldivar F Jr, Leu SY, Galassetti P, Cooper DM (2008) Effects of 30 min of aerobic exercise on gene expression in human neutrophils. J Appl Physiol (1985) 104:236–243
Rall LC, Roubenoff R, Cannon JG, Abad LW, Dinarello CA, Meydani SN (1996) Effects of progressive resistance training on immune response in aging and chronic inflammation. Med Sci Sports Exerc 28:1356–1365
Raso V, Benard G, da Silva Duarte AJ, Natale VM (2007) Effect of resistance training on immunological parameters of healthy elderly women. Med Sci Sports Exerc 39:2152–2159
Rehm K, Sunesara I, Marshall GD (2015) Increased circulating anti-inflammatory cells in marathon-trained runners. Int J Sports Med 36:832–836
Reis e Sousa C, Hieny S, Scharton-Kersten T, Jankovic D, Charest H, Germain RN, Sher A (1997) In vivo microbial stimulation induces rapid CD40 ligand-independent production of interleukin 12 by dendritic cells and their redistribution to T cell areas. J Exp Med 186:1819–1829
Renshaw M, Rockwell J, Engleman C, Gewirtz A, Katz J, Sambhara S (2002) Cutting edge: impaired Toll-like receptor expression and function in aging. J Immunol 169:4697–4701
Reyna SM, Ghosh S, Tantiwong P, Meka CS, Eagan P, Jenkinson CP, Cersosimo E, Defronzo RA, Coletta DK, Sriwijitkamol A, Musi N (2008) Elevated toll-like receptor 4 expression and signaling in muscle from insulin-resistant subjects. Diabetes 57:2595–2602
Rhind SG, Shek PN, Shinkai S, Shephard RJ (1994) Differential expression of interleukin-2 receptor alpha and beta chains in relation to natural killer cell subsets and aerobic fitness. Int J Sports Med 15:311–318
Riddell NE, Wallace GR, Van Stijn A, van Lier RA, Drayson MT, Salmon M, Bosch JA (2009) Selective β-adrenergic receptor expression on human memory CD8+ T lymphocyte subsets regulates mobilization and INF-y production. Inflamm Res 58:S256–SS60
Robinson E, Durrer C, Simtchouk S, Jung ME, Bourne JE, Voth E, Little JP (2015) Short-term high-intensity interval and moderate-intensity continuous training reduce leukocyte TLR4 in inactive adults at elevated risk of type 2 diabetes. J Appl Physiol (1985) 119:508–516
Romagnani C, Della Chiesa M, Kohler S, Moewes B, Radbruch A, Moretta L, Moretta A, Thiel A (2005) Activation of human NK cells by plasmacytoid dendritic cells and its modulation by CD4+ T helper cells and CD4+ CD25hi T regulatory cells. Eur J Immunol 35:2452–2458
Roux A, Mourin G, Larsen M, Fastenackels S, Urrutia A, Gorochov G, Autran B, Donner C, Sidi D, Sibony-Prat J, Marchant A, Stern M, Sauce D, Appay V (2013) Differential impact of age and cytomegalovirus infection on the gammadelta T cell compartment. J Immunol 191:1300–1306
Ru W, Peijie C (2009) Modulation of NKT cells and Th1/Th2 imbalance after alpha-GalCer treatment in progressive load-trained rats. Int J Biol Sci 5:338–343
Sakaguchi S, Miyara M, Costantino CM, Hafler DA (2010) FOXP3+ regulatory T cells in the human immune system. Nat Rev Immunol 10:490–500
Salmon P (2001) Effects of physical exercise on anxiety, depression, and sensitivity to stress: a unifying theory. Clin Psychol Rev 21:33–61
Sambhara S, Switzer I, Kurichh A, Miranda R, Urbanczyk L, James O, Underdown B, Klein M, Burt D (1998) Enhanced antibody and cytokine responses to influenza viral antigens in perforin-deficient mice. Cell Immunol 187:13–18
Sanchez-Correa B, Morgado S, Gayoso I, Bergua JM, Casado JG, Arcos MJ, Bengochea ML, Duran E, Solana R, Tarazona R (2011) Human NK cells in acute myeloid leukaemia patients: analysis of NK cell-activating receptors and their ligands. Cancer Immunol Immunother 60:1195–1205
Saurwein-Teissl M, Lung TL, Marx F, Gschosser C, Asch E, Blasko I, Parson W, Bock G, Schonitzer D, Trannoy E, Grubeck-Loebenstein B (2002) Lack of antibody production following immunization in old age: association with CD8(+)CD28(−) T cell clonal expansions and an imbalance in the production of Th1 and Th2 cytokines. J Immunol 168:5893–5899
Sawada SS, Muto T, Tanaka H, Lee IM, Paffenbarger RS Jr, Shindo M, Blair SN (2003) Cardiorespiratory fitness and cancer mortality in Japanese men: a prospective study. Med Sci Sports Exerc 35:1546–1550
Saxton JM, Scott EJ, Daley AJ, Woodroofe M, Mutrie N, Crank H, Powers HJ, Coleman RE (2014) Effects of an exercise and hypocaloric healthy eating intervention on indices of psychological health status, hypothalamic-pituitary-adrenal axis regulation and immune function after early-stage breast cancer: a randomised controlled trial. Breast Cancer Res 16:R39
Schaun MI, Dipp T, Rossato Jda S, Wilhelm EN, Pinto R, Rech A, Plentz RD, Homem de Bittencourt PI, Reischak-Oliveira A (2011) The effects of periodized concurrent and aerobic training on oxidative stress parameters, endothelial function and immune response in sedentary male individuals of middle age. Cell Biochem Funct 29:534–542
Schulz AR, Malzer JN, Domingo C, Jurchott K, Grutzkau A, Babel N, Nienen M, Jelinek T, Niedrig M, Thiel A (2015) Low thymic activity and dendritic cell numbers are associated with the immune response to primary viral infection in elderly humans. J Immunol 195:4699–4711
Scott MJ, Hoth JJ, Gardner SA, Peyton JC, Cheadle WG (2003) Natural killer cell activation primes macrophages to clear bacterial infection. Am Surg 69:679–686. discussion 86–87
Shaw AC, Joshi S, Greenwood H, Panda A, Lord JM (2010) Aging of the innate immune system. Curr Opin Immunol 22:507–513
Shaw AC, Panda A, Joshi SR, Qian F, Allore HG, Montgomery RR (2011) Dysregulation of human toll-like receptor function in aging. Ageing Res Rev 10:346–353
Shearer GM (1997) Th1/Th2 changes in aging. Mech Ageing Dev 94: 1–5
Shephard RJ, Futcher R (1997) Physical activity and cancer: how may protection be maximized? Crit Rev Oncog 8:219–272
Shimizu K, Kimura F, Akimoto T, Akama T, Tanabe K, Nishijima T, Kuno S, Kono I (2008) Effect of moderate exercise training on T-helper cell subpopulations in elderly people. Exerc Immunol Rev 14:24–37
Shimizu K, Suzuki N, Imai T, Aizawa K, Nanba H, Hanaoka Y, Kuno S, Mesaki N, Kono I, Akama T (2011) Monocyte and T-cell responses to exercise training in elderly subjects. J Strength Cond Res 25:2565–2572
Shimizu I, Yoshida Y, Katsuno T, Minamino T (2013) Adipose tissue inflammation in diabetes and heart failure. Microbes Infect 15:11–17
Shin YA, Lee JH, Song W, and Jun TW (2008) Exercise training improves the antioxidant enzyme activity with no changes of telomere length. Mech Ageing Dev 129: 254–260
Shinkai S, Kohno H, Kimura K, Komura T, Asai H, Inai R, Oka K, Kurokawa Y, Shephard R (1995) Physical activity and immune senescence in men. Med Sci Sports Exerc 27:1516–1526
Shodell M, Siegal FP (2002) Circulating, interferon-producing plasmacytoid dendritic cells decline during human ageing. Scand J Immunol 56:518–521
Siegal FP, Kadowaki N, Shodell M, Fitzgerald-Bocarsly PA, Shah K, Ho S, Antonenko S, Liu YJ (1999) The nature of the principal type 1 interferon-producing cells in human blood. Science 284:1835–1837
Silva LC, de Araujo AL, Fernandes JR, Matias Mde S, Silva PR, Duarte AJ, Garcez Leme LE, Benard G (2016) Moderate and intense exercise lifestyles attenuate the effects of aging on telomere length and the survival and composition of T cell subpopulations. Age (Dordr) 38:24
Sim YJ, Yu S, Yoon KJ, Loiacono CM, Kohut ML (2009) Chronic exercise reduces illness severity, decreases viral load, and results in greater anti-inflammatory effects than acute exercise during influenza infection. J Infect Dis 200:1434–1442
Simpson RJ (2011) Aging, persistent viral infections, and immunosenescence: can exercise “make space”? Exerc Sport Sci Rev 39:23–33
Simpson RJ, Florida-James GD, Cosgrove C, Whyte GP, Macrae S, Pircher H, Guy K (2007) High-intensity exercise elicits the mobilization of senescent T lymphocytes into the peripheral blood compartment in human subjects. J Appl Physiol (1985) 103:396–401
Simpson RJ, Cosgrove C, Ingram LA, Florida-James GD, Whyte GP, Pircher H, Guy K (2008) Senescent T-lymphocytes are mobilised into the peripheral blood compartment in young and older humans after exhaustive exercise. Brain Behav Immun 22:544–551
Simpson RJ, McFarlin BK, McSporran C, Spielmann G, ó Hartaigh B, Guy K (2009) Toll-like receptor expression on classic and pro-inflammatory blood monocytes after acute exercise in humans. Brain Behav Immun 23:232–239
Simpson RJ, Bigley AB, Spielmann G, LaVoy EC, Kunz H, Bollard CM (2016) Human cytomegalovirus infection and the immune response to exercise. Exerc Immunol Rev 22:8–27
Smith JK, Dykes R, Douglas JE, Krishnaswamy G, Berk S (1999) Long-term exercise and atherogenic activity of blood mononuclear cells in persons at risk of developing ischemic heart disease. JAMA 281:1722–1727
Smith TP, Kennedy SL, Fleshner M (2004) Influence of age and physical activity on the primary in vivo antibody and T cell-mediated responses in men. J Appl Physiol (1985) 97:491–498
Solana R, Mariani E (2000) NK and NK/T cells in human senescence. Vaccine 18:1613–1620
Solana R, Villanueva JL, Pena J, De la Fuente M (1991) Cell mediated immunity in ageing. Comp Biochem Physiol A Comp Physiol 99:1–4
Solana R, Tarazona R, Gayoso I, Lesur O, Dupuis G, Fulop T (2012) Innate immunosenescence: effect of aging on cells and receptors of the innate immune system in humans. Semin Immunol 24:331–341
Souza PM, Jacob-Filho W, Santarem JM, Silva AR, Li HY, Burattini MN (2008) Progressive resistance training in elderly HIV-positive patients: does it work? Clinics (Sao Paulo) 63:619–624
Spielmann G, McFarlin BK, O'Connor DP, Smith PJ, Pircher H, Simpson RJ (2011) Aerobic fitness is associated with lower proportions of senescent blood T-cells in man. Brain Behav Immun 25:1521–1529
Spielmann G, Bollard CM, Bigley AB, Hanley PJ, Blaney JW, LaVoy EC, Pircher H, Simpson RJ (2014) The effects of age and latent cytomegalovirus infection on the redeployment of CD8+ T cell subsets in response to acute exercise in humans. Brain Behav Immun 39:142–151
Sridharan A, Esposo M, Kaushal K, Tay J, Osann K, Agrawal S, Gupta S, Agrawal A (2011) Age-associated impaired plasmacytoid dendritic cell functions lead to decreased CD4 and CD8 T cell immunity. Age (Dordr) 33:363–376
Stervbo U, Bozzetti C, Baron U, Jurchott K, Meier S, Malzer JN, Nienen M, Olek S, Rachwalik D, Schulz AR, Neumann A, Babel N, Grutzkau A, Thiel A (2015a) Effects of aging on human leukocytes (part II): immunophenotyping of adaptive immune B and T cell subsets. Age (Dordr) 37:93
Stervbo U, Meier S, Malzer JN, Baron U, Bozzetti C, Jurchott K, Nienen M, Olek S, Rachwalik D, Schulz AR, Waldner JM, Neumann A, Babel N, Grutzkau A, Thiel A (2015b) Effects of aging on human leukocytes (part I): immunophenotyping of innate immune cells. Age (Dordr) 37:92
Stout-Delgado HW, Du W, Shirali AC, Booth CJ, Goldstein DR (2009) Aging promotes neutrophil-induced mortality by augmenting IL-17 production during viral infection. Cell Host Microbe 6:446–456
Suchy D, Labuzek K, Buldak L, Szkudlapski D, Okopien B (2014) Comparison of chosen activation markers of human monocytes/macrophages isolated from the peripheral blood of young and elderly volunteers. Pharmacol Rep 66:759–765
Sun JC, Lanier LL (2011) NK cell development, homeostasis and function: parallels with CD8(+) T cells. Nat Rev Immunol 11:645–657
Suzui M, Kawai T, Kimura H, Takeda K, Yagita H, Okumura K, Shek PN, Shephard RJ (2004) Natural killer cell lytic activity and CD56(dim) and CD56(bright) cell distributions during and after intensive training. J Appl Physiol (1985) 96:2167–2173
Syu GD, Chen HI, Jen CJ (2012) Differential effects of acute and chronic exercise on human neutrophil functions. Med Sci Sports Exerc 44:1021–1027
Szczepanski MJ, Szajnik M, Welsh A, Foon KA, Whiteside TL, Boyiadzis M (2010) Interleukin-15 enhances natural killer cell cytotoxicity in patients with acute myeloid leukemia by upregulating the activating NK cell receptors. Cancer Immunol Immunother 59:73–79
Taaffe DR, Harris TB, Ferrucci L, Rowe J, Seeman TE (2000) Cross-sectional and prospective relationships of interleukin-6 and C-reactive protein with physical performance in elderly persons: MacArthur studies of successful aging. J Gerontol A Biol Sci Med Sci 55:M709–M715
Takahashi M, Miyashita M, Kawanishi N, Park JH, Hayashida H, Kim HS, Nakamura Y, Sakamoto S, Suzuki K (2013) Low-volume exercise training attenuates oxidative stress and neutrophils activation in older adults. Eur J Appl Physiol 113:1117–1126
Tan CT, Wistuba-Hamprecht K, Xu W, Nyunt MS, Vasudev A, Lee BT, Pawelec G, Puan KJ, Rotzschke O, Ng TP, Larbi A (2016) Vdelta2+ and alpha/ss T cells show divergent trajectories during human aging. Oncotarget 7:44906–44918
Tarazona R, Gayoso I, Alonso C, Alonso C, Peralbo E, Casado JG, Sánchez-Correa B, Morgado S, Solana R (2009) NK Cells in Human Ageing. In: Fulop T, Franceschi C, Hirokawa K, Pawelec G (eds) Handbook on Immunosenescence: basic understanding and clinical applications. Springer, Dordrecht
Tiainen K, Hurme M, Hervonen A, Luukkaala T, Jylha M (2010) Inflammatory markers and physical performance among nonagenarians. J Gerontol A Biol Sci Med Sci 65:658–663
Timmerman KL, Flynn MG, Coen PM, Markofski MM, Pence BD (2008) Exercise training-induced lowering of inflammatory (CD14+CD16+) monocytes: a role in the anti-inflammatory influence of exercise? J Leukoc Biol 84:1271–1278
Tomasec P, Braud VM, Rickards C, Powell MB, McSharry BP, Gadola S, Cerundolo V, Borysiewicz LK, McMichael AJ, Wilkinson GW (2000) Surface expression of HLA-E, an inhibitor of natural killer cells, enhanced by human cytomegalovirus gpUL40. Science 287:1031
Turner JE, Aldred S, Witard OC, Drayson MT, Moss PM, Bosch JA (2010) Latent cytomegalovirus infection amplifies CD8 T-lymphocyte mobilisation and egress in response to exercise. Brain Behav Immun 24:1362–1370
Turner JE, Campbell JP, Edwards KM, Howarth LJ, Pawelec G, Aldred S, Moss P, Drayson MT, Burns VE, Bosch JA (2014) Rudimentary signs of immunosenescence in Cytomegalovirus-seropositive healthy young adults. Age (Dordr) 36:287–297
Uchakin PN, Parish DC, Dane FC, Uchakina ON, Scheetz AP, Agarwal NK, Smith BE (2011) Fatigue in medical residents leads to reactivation of herpes virus latency. Interdiscip Perspect Infect Dis 2011:571340
Usui T, Yoshikawa T, Orita K, Ueda SY, Katsura Y, Fujimoto S, Yoshimura M (2011) Changes in salivary antimicrobial peptides, immunoglobulin A and cortisol after prolonged strenuous exercise. Eur J Appl Physiol 111:2005–2014
Valentine RJ, Misic MM, Rosengren KS, Woods JA, Evans EM (2009) Sex impacts the relation between body composition and physical function in older adults. Menopause 16:518–523
van der Geest KS, Abdulahad WH, Tete SM, Lorencetti PG, Horst G, Bos NA, Kroesen BJ, Brouwer E, Boots AM (2014) Aging disturbs the balance between effector and regulatory CD4+ T cells. Exp Gerontol 60:190–196
van Duin D, Shaw AC (2007) Toll-like receptors in older adults. J Am Geriatr Soc 55:1438–1444
van Duin D, Allore HG, Mohanty S, Ginter S, Newman FK, Belshe RB, Medzhitov R, Shaw AC (2007) Prevaccine determination of the expression of costimulatory B7 molecules in activated monocytes predicts influenza vaccine responses in young and older adults. J Infect Dis 195:1590–1597
Vankayalapati R, Wizel B, Weis SE, Safi H, Lakey DL, Mandelboim O, Samten B, Porgador A, Barnes PF (2002) The NKp46 receptor contributes to NK cell lysis of mononuclear phagocytes infected with an intracellular bacterium. J Immunol 168:3451–3457
Vankayalapati R, Garg A, Porgador A, Griffith DE, Klucar P, Safi H, Girard WM, Cosman D, Spies T, Barnes PF (2005) Role of NK cell-activating receptors and their ligands in the lysis of mononuclear phagocytes infected with an intracellular bacterium. J Immunol 175:4611–4617
Vasudev A, Ying CT, Ayyadhury S, Puan KJ, Andiappan AK, Nyunt MS, Shadan NB, Mustafa S, Low I, Rotzschke O, Fulop T, Ng TP, Larbi A (2014) Gamma/delta T cell subsets in human aging using the classical alpha/beta T cell model. J Leukoc Biol 96:647–655
Verdoia M, Barbieri L, Di Giovine G, Marino P, Suryapranata H, De Luca G, Group Novara Atherosclerosis Study (2016) Neutrophil to lymphocyte ratio and the extent of coronary artery disease: results from a large cohort study. Angiology 67:75–82
Verschoor CP, Johnstone J, Millar J, Parsons R, Lelic A, Loeb M, Bramson JL, Bowdish DM (2014) Alterations to the frequency and function of peripheral blood monocytes and associations with chronic disease in the advanced-age, frail elderly. PLoS One 9:e104522
Verschoor CP, Loukov D, Naidoo A, Puchta A, Johnstone J, Millar J, Lelic A, Novakowski KE, Dorrington MG, Loeb M, Bramson JL, Bowdish DM (2015) Circulating TNF and mitochondrial DNA are major determinants of neutrophil phenotype in the advanced-age, frail elderly. Mol Immunol 65:148–156
Villanueva JL, Solana R, Alonso MC, Pena J (1990) Changes in the expression of HLA-class II antigens on peripheral blood monocytes from aged humans. Dis Markers 8:85–91
Villegas FR, Coca S, Villarrubia VG, Jimenez R, Chillon MJ, Jareno J, Zuil M, Callol L (2002) Prognostic significance of tumor infiltrating natural killer cells subset CD57 in patients with squamous cell lung cancer. Lung Cancer 35:23–28
Vivier E, Raulet DH, Moretta A, Caligiuri MA, Zitvogel L, Lanier LL, Yokoyama WM, Ugolini S (2011) Innate or adaptive immunity? The example of natural killer cells. Science 331:44–49
Walsh NP, Gleeson M, Shephard RJ, Gleeson M, Woods JA, Bishop NC, Fleshner M, Green C, Pedersen BK, Hoffman-Goetz L, Rogers CJ, Northoff H, Abbasi A, Simon P (2011) Position statement. Part one: immune function and exercise. Exerc Immunol Rev 17:6–63
Wang JS, Weng TP (2011) Hypoxic exercise training promotes antitumour cytotoxicity of natural killer cells in young men. Clin Sci (Lond) 121:343–353
Wang L, Xie Y, Zhu LJ, Chang TT, Mao YQ, Li J (2010) An association between immunosenescence and CD4(+)CD25(+) regulatory T cells: a systematic review. Biomed Environ Sci 23:327–332
Wang J, Song H, Tang X, Yang Y, Vieira VJ, Niu Y, Ma Y (2012) Effect of exercise training intensity on murine T-regulatory cells and vaccination response. Scand J Med Sci Sports 22:643–652
Wendt K, Wilk E, Buyny S, Buer J, Schmidt RE, Jacobs R (2006) Gene and protein characteristics reflect functional diversity of CD56dim and CD56bright NK cells. J Leukoc Biol 80:1529–1541
Wenisch C, Patruta S, Daxbock F, Krause R, Horl W (2000) Effect of age on human neutrophil function. J Leukoc Biol 67:40–45
Westera L, van Hoeven V, Drylewicz J, Spierenburg G, van Velzen JF, de Boer RJ, Tesselaar K, Borghans JA (2015) Lymphocyte maintenance during healthy aging requires no substantial alterations in cellular turnover. Aging Cell 14:219–227
West-Wright CN, Henderson KD, Sullivan-Halley J, Ursin G, Deapen D, Neuhausen S, Reynolds P, Chang E, Ma H, Bernstein L (2009) Long-term and recent recreational physical activity and survival after breast cancer: the California Teachers Study. Cancer Epidemiol Biomark Prev 18:2851–2859
Wilson LD, Zaldivar FP, Schwindt CD, Wang-Rodriguez J, Cooper DM (2009) Circulating T-regulatory cells, exercise and the elite adolescent swimmer. Pediatr Exerc Sci 21:305–317
Wong CM, Lai HK, Ou CQ, Ho SY, Chan KP, Thach TQ, Yang L, Chau YK, Lam TH, Hedley AJ, Peiris JS (2008) Is exercise protective against influenza-associated mortality? PLoS One 3:e2108
Woods JA, Ceddia MA, Wolters BW, Evans JK, Lu Q, McAuley E (1999) Effects of 6 months of moderate aerobic exercise training on immune function in the elderly. Mech Ageing Dev 109:1–19
Woods J, Lu Q, Ceddia MA, Lowder T (2000) Special feature for the Olympics: effects of exercise on the immune system: exercise-induced modulation of macrophage function. Immunol Cell Biol 78:545–553
Woods JA, Keylock KT, Lowder T, Vieira VJ, Zelkovich W, Dumich S, Colantuano K, Lyons K, Leifheit K, Cook M, Chapman-Novakofski K, McAuley E (2009) Cardiovascular exercise training extends influenza vaccine seroprotection in sedentary older adults: the immune function intervention trial. J Am Geriatr Soc 57:2183–2191
Wood WA, Deal AM, Reeve BB, Abernethy AP, Basch E, Mitchell SA, Shatten C, Hie Kim Y, Whitley J, Serody JS, Shea T, and Battaglini C (2013). Cardiopulmonary fitness in patients undergoing hematopoietic SCT: a pilot study. Bone Marrow Transplant 48: 1342–1349.
Wu D, Meydani SN (2008) Age-associated changes in immune and inflammatory responses: impact of vitamin E intervention. J Leukoc Biol 84:900–914
Xu X, Beckman I, Bradley J (1993) Age-related changes in the expression of IL-2 and high-affinity IL-2 binding sites. Int Arch Allergy Immunol 102:224–231
Yan H, Kuroiwa A, Tanaka H, Shindo M, Kiyonaga A, Nagayama A (2001) Effect of moderate exercise on immune senescence in men. Eur J Appl Physiol 86:105–111
Yasui T, Uemura H, Tomita J, Miyatani Y, Yamada M, Kuwahara A, Matsuzaki T, Maegawa M, Tsuchiya N, Yuzurihara M, Takeda S, Irahara M (2006) Association of interleukin-8 with hot flashes in premenopausal, perimenopausal, and postmenopausal women and bilateral oophorectomized women. J Clin Endocrinol Metab 91:4805–4808
Yeh SH, Chuang H, Lin LW, Hsiao CY, Eng HL (2006) Regular tai chi chuan exercise enhances functional mobility and CD4CD25 regulatory T cells. Br J Sports Med 40:239–243
Yeh SH, Chuang H, Lin LW, Hsiao CY, Wang PW, Liu RT, Yang KD (2009) Regular tai chi Chuan exercise improves T cell helper function of patients with type 2 diabetes mellitus with an increase in T-bet transcription factor and IL-12 production. Br J Sports Med 43:845–850
Zhang Y, Wallace DL, de Lara CM, Ghattas H, Asquith B, Worth A, Griffin GE, Taylor GP, Tough DF, Beverley PC, Macallan DC (2007) In vivo kinetics of human natural killer cells: the effects of ageing and acute and chronic viral infection. Immunology 121:258–265
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Bigley, A.B., Baker, F.L., Spielmann, G., Simpson, R. (2019). Aging Immunity and the Impact of Physical Exercise. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook of Immunosenescence. Springer, Cham. https://doi.org/10.1007/978-3-319-99375-1_165
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