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Handbook on Immunosenescence pp 1247–1272Cite as

Insulin Resistance, Chronic Inflammation and the Link with Immunosenescence

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Abstract

Ageing is associated with an activation of the innate immune system which manifests in a chronic, low-grade, inflammatory status common in elderly individuals. Age-related inflammatory activity, as measured by increased serum levels of proinflammatory cytokines and activation of inflammatory signalling pathways, leads to long-term tissue damage and is thought to contribute to—and occur as a consequence of—immunosenescence. In addition to immune system deregulation, this elevated inflammatory status is associated with a number of age-related diseases and conditions, including neurodegeneration, atherosclerosis, sarcopenia, and diabetes, and is a main contributor to the age-related decline in physical function and vitality known as frailty. Inflammation is also an important component of the insulin resistance syndrome. In addition to age, a major risk factor for the development of the insulin resistance syndrome is obesity. Obesity is associated with increased proinflammatory cytokine production and altered regulation of both pro and antiinflammatory molecules, including a class of adipose-derived signalling molecules termed adipocytokines. The increased production of inflammatory mol- ecules in obese and nonobese insulin resistant elderly individuals may contribute to age-related decline in health, including dysfunction of the immune system. Antiinflammatory strategies for the treatment of the insulin resistance syndrome may promote remodelling of the immune system thereby contributing to remediation of immunity and prevention of frailty in the elderly population.

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References

  • Arita Y, Kihara S, Ouchi N, Takahashi M, Maeda K, Miyagawa J, Hotta K, Shimomura I, Nakamura T, Miyaoka K, Kuriyama H, Nishida M, Yamashita S, Okubo K, Matsubara K, Muraguchi M, Ohmoto Y, Funahashi T, Matsuzawa Y (1999) Paradoxical decrease of an adipose-specific protein, adiponectin, in obesity. Biochem Biophys Res Commun 257(1):79–83

    PubMed  CAS  Google Scholar 

  • Auwerx J, Cock TA, Knouff C (2003) PPAR-gamma: a thrifty transcription factor. Nucl Recept Signal 1:e006

    PubMed  Google Scholar 

  • Barbieri M, Bonafe M, Franceschi C, Paolisso G (2003) Insulin/IGF-I-signaling pathway: an evolutionarily conserved mechanism of longevity from yeast to humans. Am J Physiol Endocrinol Metab 285(5):E1064–E1071 Review

    CAS  Google Scholar 

  • Bartali B, Benvenuti E, Corsi AM, Bandinelli S, Russo CR, Di Iorio A, Lauretani F, Ferrucci L (2002) Changes in anthropometric measures in men and women across the life-span: findings from the InCHIANTI study. Soz Praventivmed 47(5):336–348

    PubMed  Google Scholar 

  • Berger J, Moller DE (2002) The mechanisms of action of ppars. Annu Rev Med 53:409–435

    PubMed  CAS  Google Scholar 

  • Blair SN, Wei M (2000) Sedentary habits, health, and function in older women and men. Am J Health Promot 15(1):1–8 Review

    PubMed  CAS  Google Scholar 

  • Boden G, She P, Mozzoli M, Cheung P, Gumireddy K, Reddy P, Xiang X, Luo Z, Ruderman N (2005) Free fatty acids produce insulin resistance and activate the proinflammatory nuclear factor-kappaB pathway in rat liver. Diabetes 54(12):3458–3465

    PubMed  CAS  Google Scholar 

  • Bogden JD, Oleske JM, Lavenhar MA, Munves EM, Kemp FW, Bruening KS, Holding KJ, Denny TN, Guarino MA, Krieger LM et al. (1988) Zinc and immunocompetence in elderly people: effects of zinc supplementation for 3 months. Am J Clin Nutr 48(3):655–663

    PubMed  CAS  Google Scholar 

  • Bonafe M, Olivieri F, Cavallone L, Giovagnetti S, Mayegiani F, Cardelli M, Pieri C, Marra M, Antonicelli R, Lisa R, Rizzo MR, Paolisso G, Monti D, Franceschi C (2001) A gender-dependent genetic predisposition to produce high levels of IL-6 is detrimental for longevity. Eur J Immunol 31(8):2357–2361

    PubMed  CAS  Google Scholar 

  • Borissova AM, Tankova T, Kirilov G, Dakovska L, Kovacheva R (2003) The effect of vitamin D3 on insulin secretion and peripheral insulin sensitivity in type 2 diabetic patients. Int J Clin Pract 57(4):258–261

    PubMed  CAS  Google Scholar 

  • Bosy-Westphal A, Reinecke U, Schlorke T, Illner K, Kutzner D, Heller M, Muller MJ (2004) Effect of organ and tissue masses on resting energy expenditure in underweight, normal weight and obese adults. Int J Obes Relat Metab Disord 28(1):72–79

    PubMed  CAS  Google Scholar 

  • Boucher BJ, Mannan N, Noonan K, Hales CN, Evans SJ (1995) Glucose intolerance and impairment of insulin secretion in relation to vitamin D deficiency in east London Asians. Diabetologia 38(10):1239–1245

    PubMed  CAS  Google Scholar 

  • Briefel RR, Bialostosky K, Kennedy-Stephenson J, McDowell MA, Ervin RB, Wright JD (2000) Zinc intake of the U.S. population: findings from the third National Health and Nutrition Examination Survey, (1988–1994). J Nutr 130(5S Suppl):1367S–1373S

    PubMed  CAS  Google Scholar 

  • Browning LM, Krebs JD, Moore CS, Mishra GD, O’Connell MA, Jebb SA (2007) The impact of long chain n-3 polyunsaturated fatty acid supplementation on inflammation, insulin sensitivity and CVD risk in a group of overweight women with an inflammatory phenotype. Diabetes Obes Metab 9(1):70–80

    PubMed  CAS  Google Scholar 

  • Browning LM (2003) n-3 Polyunsaturated fatty acids, inflammation and obesity-related disease. Proc Nutr Soc 62(2):447–453

    PubMed  CAS  Google Scholar 

  • Bruun JM, Lihn AS, Verdich C, Pedersen SB, Toubro S, Astrup A, Richelsen B (2003) Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans. Am J Physiol Endocrinol Metab 285(3):E527–E533

    PubMed  CAS  Google Scholar 

  • Cakman I, Rohwer J, Schutz RM, Kirchner H, Rink L (1996) Dysregulation between TH1 and TH2 T cell subpopulations in the elderly. Mech Ageing Dev 87(3):197–209

    PubMed  CAS  Google Scholar 

  • Calder PC (2003) New evidence in support of the cardiovascular benefit of long-chain n-3 fatty acids. Ital Heart J 4(7):427–429

    PubMed  Google Scholar 

  • Calder PC (2005) Polyunsaturated fatty acids and inflammation. Biochem Soc Trans. 33(Pt 2): 423–427 Review

    PubMed  CAS  Google Scholar 

  • Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579–591

    PubMed  CAS  Google Scholar 

  • Calvano SE, Xiao W, Richards DR, Felciano RM, Baker HV, Cho RJ, Chen RO, Brownstein BH, Cobb JP, Tschoeke K, Miller-Graziano C, Moldawer LL, Mindrinos MN, Davis RW, Tompkins RG, Lowry SF (2005) Inflammation and host response to injury—large scale collaborative research program. Nature 437:1032–1037

    PubMed  CAS  Google Scholar 

  • Chandra RK (2003) Nutrient regulation of immune functions. Forum Nutr 56:147–148 Review

    PubMed  CAS  Google Scholar 

  • Church TS, Barlow CE, Earnest CP, Kampert JB, Priest EL, Blair SN (2002) Associations between cardiorespiratory fitness and C-reactive protein in men. Arterioscler Thromb Vasc Biol 22(11):1869–1876

    PubMed  CAS  Google Scholar 

  • Cippitelli M, Santoni A (1998) Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol 28(10):3017–3030

    PubMed  CAS  Google Scholar 

  • Cohen HJ (1997) Cancer and the functional status of the elderly. Cancer 80(10):1883–1886

    PubMed  CAS  Google Scholar 

  • Cossarizza A, Ortolani C, Monti D, Franceschi C (1997) Cytometric analysis of immunosenescence. Cytometry 27(4):297–313 Review

    PubMed  CAS  Google Scholar 

  • Croker BA, Krebs DL, Zhang JG, Wormald S, Willson TA, Stanley EG, Robb L, Greenhalgh CJ, Forster I, Clausen BE, Nicola NA, Metcalf D, Hilton DJ, Roberts AW, Alexander WS (2003) SOCS3 negatively regulates IL-6 signaling in vivo. Nat Immunol 4(6):540–545

    PubMed  CAS  Google Scholar 

  • Delerive P, De Bosscher K, Besnard S, Vanden Berghe W, Peters JM, Gonzalez FJ, Fruchart JC, Tedgui A, Haegeman G, Staels B (1999) Peroxisome proliferator-activated receptor alpha negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1. J Biol Chem 274(45):32048–32054

    PubMed  CAS  Google Scholar 

  • Delerive P, Gervois P, Fruchart JC, Staels B (2000) Induction of IkappaBalpha expression as a mechanism contributing to the anti-inflammatory activities of peroxisome proliferator-activated receptor-alpha activators. J Biol Chem 275(47):36703–36707

    PubMed  CAS  Google Scholar 

  • Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W (1996) The PPARalphaleukotriene B4 pathway to inflammation control. Nature 384:39–43

    PubMed  CAS  Google Scholar 

  • Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI (1999) Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest 103(2):253–259

    PubMed  CAS  Google Scholar 

  • Dunn AL, Marcus BH, Kampert JB, Garcia ME, Kohl HW 3rd, Blair SN (1999) Comparison of lifestyle and structured interventions to increase physical activity and cardiorespiratory fitness: a randomized trial. JAMA 281(4):327–334

    PubMed  CAS  Google Scholar 

  • Effros RB, Pawelec G (1997) Replicative senenscence of T lymphocytes: does the Hayflick limit lead to immune exhaustion? Immunol Today 18:450–454

    PubMed  CAS  Google Scholar 

  • 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 Cytok Res 12(4):225–230

    CAS  Google Scholar 

  • Estrach C, Abernethy VE, Dawson JK (2004) Infections and anti-TNF therapy: strategies for screening based on clinical experience. Rheumatology (Oxford) 43:115–116

    CAS  Google Scholar 

  • Fantuzzi G, Sennello JA, Batra A, Fedke I, Lehr HA, Zeitz M, Siegmund B (2005) Defining the role of T cell-derived leptin in the modulation of hepatic or intestinal inflammation in mice. Clin Exp Immunol 142(1):31–38

    PubMed  CAS  Google Scholar 

  • Farooqi IS, Jebb SA, Langmack G, Lawrence E, Cheetham CH, Prentice AM, Hughes IA, McCamish MA, O’Rahilly S (1999) Effects of recombinant leptin therapy in a child with congenital leptin deficiency. N Engl J Med 341(12):879–884

    PubMed  CAS  Google Scholar 

  • Farooqi IS, Matarese G, Lord GM, Keogh JM, Lawrence E, Agwu C, Sanna V, Jebb SA, Perna F, Fontana S, Lechler RI, DePaoli AM, O’Rahilly S (2002) Beneficial effects of leptin on obesity, T cell hyporesponsiveness, and neuroendocrine/metabolic dysfunction of human congenital leptin deficiency. J Clin Invest 110(8):1093–10103

    PubMed  CAS  Google Scholar 

  • Fasciano S, Li L (2006) Intervention of Toll-like receptor-mediated human innate immunity and inflammation by synthetic compounds and naturally occurring products. Curr Med Chem 13:1389–1395

    PubMed  CAS  Google Scholar 

  • Fasshauer M, Kralisch S, Klier M, Lossner U, Bluher M, Klein J, Paschke R (2003) Adiponectin gene expression and secretion is inhibited by interleukin-6 in 3T3-L1 adipocytes. Biochem Biophys Res Commun 301(4):1045–1050

    PubMed  CAS  Google Scholar 

  • Ferrucci L, Harris TB, Guralnik JM, Tracy RP, Corti MC, Cohen HJ, Penninx B, Pahor M, Wallace R, Havlik RJ (1999) Serum IL-6 level and the development of disability in older persons. J Am Geriatr Soc 47(6):639–646

    PubMed  CAS  Google Scholar 

  • Forman BM, Tontonoz P, Chen J, Brun RP, Spiegelman BM, Evans RM (1995) 15-deoxy-∆-12,14,- prostaglandin J2 is a ligand for the adipocytre determination factor PPARγ. Cell 83:803–812

    PubMed  CAS  Google Scholar 

  • Ford ES (2002) Does exercise reduce inflammation? Physical activity and C-reactive protein among U.S. adults. Epidemiology 13(5):561–568

    PubMed  Google Scholar 

  • 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 Review

    PubMed  CAS  Google Scholar 

  • Franceschi C, Capri M, Monti D, Giunta S, Olivieri F, Sevini F, Panagiota Panourgia M, Invidia L, Celani L, Scurti M, Cevenini E, Castellani GC, Salvioli S (2007) Inflammaging and antiinflammaging: A systemic perspective on aging and longevity emerged from studies in humans. Mech Ageing Dev 128:92–105

    PubMed  CAS  Google Scholar 

  • Fried LP, Young Y, Rubin G, Bandeen-Roche K (2001) WHAS II Collaborative Research Group. Self-reported preclinical disability identifies older women with early declines in performance and early disease. J Clin Epidemiol 54(9):889–901

    PubMed  CAS  Google Scholar 

  • Gao Z, Hwang D, Bataille F et al. (2002) Serine phosphorylation of insulin receptor substrate 1 (IRS-1) by inhibitor KappaB kinase (IKK) complex. J Biol Chem 277:48115–48121

    PubMed  CAS  Google Scholar 

  • Gedik O, Akalin S (1986) Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man. Diabetologia 29(3):142–145

    PubMed  CAS  Google Scholar 

  • Gervois P, Kleemann R, Pilon A, Percevault F, Koenig W, Staels B, Kooistra T (2004) Global suppression of IL-6-induced acute phase response gene expression after chronic in vivo treatment with the peroxisome proliferator-activated receptor-alpha activator fenofibrate. J Biol Chem 279(16):16154–16160

    PubMed  CAS  Google Scholar 

  • Giacconi R, Cipriano C, Albanese F, Boccoli G, Saba V, Olivieri F, Franceschi C, Mocchegiani E (2004) The -174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing. Exp Gerontol 39(4):621–628

    PubMed  CAS  Google Scholar 

  • Ginaldi L, De Martinis M, Monti D, Franceschi C (2005) Chronic antigenic load and apoptosis in immunosenescence. Trends Immunol 26(2):79–84

    PubMed  CAS  Google Scholar 

  • 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(7):748–754

    PubMed  CAS  Google Scholar 

  • Hadrup SR, Strindhall J, Kollgaard T, Seremet T, Johansson B, Pawelec G, thor Straten P, Wikby A (2006) Longitudinal studies of clonally expanded CD8 T cells reveal a repertoire shrinkage predicting mortality and an increased number of dysfunctional cytomegalovirus-specific T cells in the very elderly. J Immunol 176:2645–2653

    PubMed  CAS  Google Scholar 

  • Harris SG, Phipps RP (2001) The nuclear receptor PPAR gamma is expressed by mouse T lymphocytes and PPAR gamma agonists induce apoptosis. Eur J Immunol 31(4):1098–10105

    PubMed  CAS  Google Scholar 

  • Hirosumi J, Tuncman G, Chang L et al. (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333–336

    PubMed  CAS  Google Scholar 

  • Hotamisligil GS, Johnson RS, Distel RF et al. (1996) Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein. Science 274:1377–1379

    PubMed  CAS  Google Scholar 

  • Hotamisligil GS, Shargill NS, Spiegelman BM (1993) Adipose expression of tumor necrosis factor- alpha: direct role in obesity-linked insulin resistance. Science 259(5091):87–91

    PubMed  CAS  Google Scholar 

  • Huang JT, Welch JS, Ricote M, Binder CJ, Willson TM, Kelly C, Witztum JL, Funk CD, Conrad D, Glass CK (1999) Interleukin-4-dependent production of PPAR-gamma ligands in macrophages by 12/15-lipoxygenase. Nature 400(6742):378–382

    PubMed  CAS  Google Scholar 

  • Ikemoto S, Takahashi M, Tsunoda N, Maruyama K, Itakura H, Ezaki O (1996) High-fate dietinduced hyperglycemia and obesity in mice: differential effects of dietary oils. Metabolism 45:1593–1546

    Google Scholar 

  • Isaia G, Giorgino R, Adami S (2001) High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 24(8):1496

    PubMed  CAS  Google Scholar 

  • Iwaki M, Matsuda M, Maeda N, Funahashi T, Matsuzawa Y, Makishima M, Shimomura I (2003) Induction of adiponectin, a fat-derived antidiabetic and antiatherogenic factor, by nuclear receptors. Diabetes 52(7):1655–1663

    PubMed  CAS  Google Scholar 

  • Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82–86

    PubMed  CAS  Google Scholar 

  • Jones DC, Manning BM, Daynes RA (2002) A role for the peroxisome proliferator-activated receptor α in T-cell physiology and ageing immunobiology. Proc Nutr Soc 61:363–369

    PubMed  CAS  Google Scholar 

  • Jucker BM, Cline GW, Burucci N, Shuclman GI (1999) Differential effects of safflower oil versus fish oil feeding on insulin-stimulated glycogen synthesis, glycolysis, and pyruvate dehydrogenase flux in skeletal muscle: a 13C nuclear magnetic resonance study. Diabetes 48:134–140

    PubMed  CAS  Google Scholar 

  • Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106(4):473–481 Review

    PubMed  CAS  Google Scholar 

  • Kanda H, Tateya S, Tamori Y, Kotani K, Hiasa K, Kitazawa R, Kitazawa S, Miyachi H, Maeda S, Egashira K, Kasuga M (2006) MCP-1 contributes to macrophage infiltration into adipose tissue, insulin resistance, and hepatic steatosis in obesity. J Clin Invest 116(6):1494–1505

    PubMed  CAS  Google Scholar 

  • Kern PA, Saghizadeh M, Ong JM, Bosch RJ, Deem R, Simsolo RB (1995) The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase. J Clin Invest 95(5):2111–21119

    PubMed  CAS  Google Scholar 

  • Khan N, Shariff N, Cobbold M, Bruton R, Ainsworth JA, Sinclair AJ, Nayak L, Moss PA (2002) Cytomegalovirus seropositivity drives the CD8 T cell repertoire toward greater clonality in healthy elderly individuals. J Immunol 169:1984–1992

    PubMed  CAS  Google Scholar 

  • Kitano H, Oda K (2006) Robustness trade-offs and host-microbial symbiosis in the immune system. Mol Syst Biol doi:10.1038/msb4100039

    Google Scholar 

  • Kumar S, Davies M, Zakaria Y, Mawer EB, Gordon C, Olukoga AO, Boulton AJ (1994) Improvement in glucose tolerance and beta-cell function in a patient with vitamin D deficiency during treatment with vitamin D. Postgrad Med J 70(824):440–443

    PubMed  CAS  Google Scholar 

  • La Cava A, Matarese G, Ebling FM, Hahn BH (2003) Leptin-based immune intervention: Current status and future directions. Curr Opin Invest Drugs 4(11):1327–1332

    CAS  Google Scholar 

  • La Cava A, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4(5):371–379 Review

    PubMed  CAS  Google Scholar 

  • Lakka TA, Laaksonen DE, Lakka HM, Mannikko N, Niskanen LK, Rauramaa R, Salonen JT (2003) Sedentary lifestyle, poor cardiorespiratory fitness, and the metabolic syndrome. Med Sci Sports Exerc 35(8):1279–1286

    PubMed  Google Scholar 

  • Lee S, Clark SA, Gill RK, Christakos S (1994) 1,25-Dihydroxyvitamin D3 and pancreatic betacell function: vitamin D receptors, gene expression, and insulin secretion. Endocrinology 134(4):1602–1610

    PubMed  CAS  Google Scholar 

  • Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA (1997) Peroxisome proliferator- activated receptors α and β are activated by indomethacin and other non-steroidal antiinflammatory drugs. J Biol Chem 272:3406–3410

    PubMed  CAS  Google Scholar 

  • Leininger MT, Portocarrero CP, Houseknecht KL (1999) Peroxisome proliferator-activated receptor gamma 1 expressionin procine white bolld cells: dynamic regulation with acute endotoxemia. Biochem Biophys Res Commun 263:749–753

    PubMed  CAS  Google Scholar 

  • Lesourd B (1999) Immune response during disease and recovery in the elderly. Proc Nutr Soc 58(1):85–98 Review

    CAS  Google Scholar 

  • Lio D, Candore G, Colombo A, Colonna Romano G, Gervasi F, Marino V, Scola L, Caruso C (2001) A genetically determined high setting of TNF-alpha influences immunologic parameters of HLA-B8,DR3 positive subjects: implications for autoimmunity. Hum Immunol 62(7):705–713

    PubMed  CAS  Google Scholar 

  • Lord GM, Matarese G, Howard JK, Baker RJ, Bloom SR, Lechler RI (1998) Leptin modulates the T-cell immune response and reverses starvation-induced immunosuppression. Nature 394(6696):897–901

    PubMed  CAS  Google Scholar 

  • Maeda N, Takahashi M, Funahashi T, Kihara S, Nishizawa H, Kishida K, Nagaretani H, Matsuda M, Komuro R, Ouchi N, Kuriyama H, Hotta K, Nakamura T, Shimomura I, Matsuzawa Y (2001) PPARgamma ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50(9):2094–2099

    PubMed  CAS  Google Scholar 

  • Maeda N, Shimomura I, Kishida K, Nishizawa H, Matsuda M, Nagaretani H, Furuyama N, Kondo H, Takahashi M, Arita Y, Komuro R, Ouchi N, Kihara S, Tochino Y, Okutomi K, Horie M, Takeda S, Aoyama T, Funahashi T, Matsuzawa Y (2002) Diet-induced insulin resistance in mice lacking adiponectin/ACRP30. Nat Med 8(7):731–737

    PubMed  CAS  Google Scholar 

  • Mandel MA, Mahmoud AA (1978) Impairment of cell-mediated immunity in mutation diabetic mice (db/db). J Immunol 120(4):1375–1377

    PubMed  CAS  Google Scholar 

  • Mannino DM, Mott J, Ferdinands JM, Camargo CA, Friedman M, Greves HM, Redd SC (2006) Boys with high body masses have an increased risk of developing asthma: findings from the National Longitudinal Survey of Youth (NLSY). Int J Obes (Lond) 30(1):6–13

    CAS  Google Scholar 

  • Mathieu C, Adorini L (2002) The coming of age of 1,25-dihydroxyvitamin D(3) analogs as immunomodulatory agents. Trends Mol Med 8(4):174–179

    PubMed  CAS  Google Scholar 

  • Mazzatti DJ, Malavolta M, White AJ, Costarelli L, Giacconi R, Muti E, Cipriano C, Powell JR, Mocchegiani E (2007) Differential effects of in vitro zinc treatment on gene expression in peripheral blood mononuclear cells derived from young and elderly individuals. Rejuvenation Res 10(4):603–620

    PubMed  CAS  Google Scholar 

  • Mazzeo RS (1994) The influence of exercise and aging on immune function. Med Sci Sports Exerc 26(5):586–592 Review

    PubMed  CAS  Google Scholar 

  • Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1(2):135–145 Review

    PubMed  CAS  Google Scholar 

  • Miller RA, Stutman O (1981) Decline, in aging mice, of the anti-2,4,6-trinitrophenyl (TNP) cytotoxic T cell response attributable to loss of Lyt-2-, interleukin 2-producing helper cell function. Eur J Immunol 11(10):751–756

    PubMed  CAS  Google Scholar 

  • Moyna NM, Acker GR, Fulton JR, Weber K, Goss FL, Robertson RJ, Tollerud DJ, Rabin BS (1996) Lymphocyte function and cytokine production during incremental exercise in active and sedentary males and females. Int J Sports Med 17(8):585–591

    PubMed  CAS  Google Scholar 

  • Mueller E, Smith M, Sarraf P, Kroll T, Aiyer A, Kaufman DS, Oh W, Demetri G, Figg WD, Zhou XP, Eng C, Spiegelman BM, Kantoff PW (2000) Effects of ligand activation of peroxisome proliferator-activated receptor gamma in human prostate cancer. Proc Nat Acad Sci U S A 97:10990–10995

    CAS  Google Scholar 

  • Neschen S, Morino K, Dong J, Wang-Fischer Y, Cline GW, Romanelli AJ, Rossbacher JC, Moore IK, Regittnig W, Munoz DS, Kim JH, Shulman GI (2007) N-3 fatty acids preserve insulin sensitivity in vivo in a peroxisome proliferator-activated receptor-α-dependent manner. Diabetes 56:1034–1041

    PubMed  CAS  Google Scholar 

  • Ofei F, Hurel S, Newkirk J, Sopwith M, Taylor R (1996) Effects of an engineered human anti- TNF-alpha antibody (CDP571) on insulin sensitivity and glycemic control in patients with NIDDM. Diabetes 45(7):881–885

    PubMed  Google Scholar 

  • Ouyang Q, Wagner WM, Wikby A, Walter S, Aubert G, Dodi AI, Travers P, Pawelec G (2003) Large numbers of dysfunctional CD8+ T lymphocytes bearing receptors for a single dominant CMV epitope in the very old. J Clin Immunol 23:247–257

    PubMed  CAS  Google Scholar 

  • Padilla J, Kaur K, Harris SG, Phipps RP (2000) PPAR-gamma-mediated regulation of normal and malignant B lineage cells. Ann N Y Acad Sci 905:97–109

    PubMed  CAS  Google Scholar 

  • Paquot N, Castillo MJ, Lefebvre PJ, Scheen AJ (2000) No increased insulin sensitivity after a single intravenous administration of a recombinant human tumor necrosis factor receptor: Fc fusion protein in obese insulin-resistant patients. J Clin Endocrinol Metab 85(3):1316–1319

    PubMed  CAS  Google Scholar 

  • Pawelec G, Hirokawa K, Fulop T (2001) Altered T cell signalling in ageing. Mech Ageing Dev 122:1613–1637

    CAS  Google Scholar 

  • Pawelec G, Koch S, Griesemann H, Rehbein A, Hahnel K, Gouttefangeas C (2006) Immunosenescence, suppression and tumour progression. Cancer Immunol Immunother 55:981–986

    PubMed  CAS  Google Scholar 

  • Pawelec, G, Solana, R (1997) Immunosenescence. Immunol Today 18:514–516

    PubMed  CAS  Google Scholar 

  • Peralta S, Carrascosa JM, Gallardo N, Ros M, Arribas C (2002) Ageing increases SOCS-3 expression in rat hypothalamus: effects of food restriction. Biochem Biophys Res Commun 296(2):425–428

    PubMed  CAS  Google Scholar 

  • Petersen KF, Befroy D, Dufour S, Dziura J, Ariyan C, Rothman DL, DiPietro L, Cline GW, Shulman GI (2003) Mitochondrial dysfunction in the elderly: possible role in insulin resistance. Science 300(5622):1140–1142

    PubMed  CAS  Google Scholar 

  • Pischon T, Mohlig M, Hoffmann K, Spranger J, Weikert C, Willich SN, Pfeiffer AF, Boeing H (2007) Comparison of relative and attributable risk of myocardial infarction and stroke according to C-reactive protein and low-density lipoprotein cholesterol levels. Eur J Epidemiol [Epub ahead of print]

    Google Scholar 

  • Pittas AG, Dawson-Hughes B, Li T, Van Dam RM, Willett WC, Manson JE, Hu FB (2006) Vitamin D and calcium intake in relation to type 2 diabetes in women. Diabetes Care 29(3):650–656

    PubMed  CAS  Google Scholar 

  • Poynter ME, Daynes RA (1998) Peroxisome proliferator-activated receptor a activation modulates cellular redox status, represses nuclear factor-kB signalling, and reduces inflammatory cytokine production in aging. J Biol Chem 273(49):32833–32841

    PubMed  CAS  Google Scholar 

  • Rabinovitch A, Suarez-Pinzon WL, Sooy K, Strynadka K, Christakos S (2001) Expression of calbindin- D(28k) in a pancreatic islet beta-cell line protects against cytokine-induced apoptosis and necrosis. Endocrinology 142(8):3649–3655

    PubMed  CAS  Google Scholar 

  • 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(2):331–342

    PubMed  CAS  Google Scholar 

  • Ricote M, Huang J, Fajas L, Li A, Welch J, Najib J, Witztum JL, Auwerx J, Palinski W, Glass CK (1998) Expression of the peroxisome proliferator-activated receptor gamma in human atherosclerosis and regulation in macrophages by colony stimulating factors and oxidized low density lipoprotein. Proc Natl Acad Sci U S A 95:7614–7619

    PubMed  CAS  Google Scholar 

  • Rink L, Gabriel P (2001) Extracellular and immunological actions of zinc. Biometals 14: 367–383

    PubMed  CAS  Google Scholar 

  • Rink L, Gabriel P (2000) Zinc and the immune system. Proc Nutr Soc 59:541–552

    PubMed  CAS  Google Scholar 

  • Rink L, Cakman I, Kirchner H (1998) Altered cytokine production in the elderly. Mech Ageing Dev 102(2–3):199–209 Review

    PubMed  CAS  Google Scholar 

  • Rui L, Yuan M, Frantz D, Shoelson S, White MF (2002) SOCS-1 and SOCS-3 block insulin signaling by ubiquitin-mediated degradation of IRS1 and IRS2. J Biol Chem 277(44):42394–42398

    PubMed  CAS  Google Scholar 

  • Shephard RJ, Shek PN (1995) Exercise, aging and immune function. Int J Sports Med 16(1):1–6 Review

    PubMed  CAS  Google Scholar 

  • Shi H, Kokoeva MV, Inouye K, Tzameli I, Yin H, Flier JS (2006) TLR4 links innate immunity and fatty acid-induced insulin resistance. J Clin Invest 116(11):3015–3025

    PubMed  CAS  Google Scholar 

  • Shinkai S, Konishi M, Shephard RJ (1998) Aging and immune response to exercise. Can J Physiol Pharmacol 76(5):562–572 Review

    PubMed  CAS  Google Scholar 

  • Shoelson SE, Lee J, Yuan M (2003) Inflammation and the IKK beta/I kappa B/NF-kappa B axis in obesity- and diet-induced insulin resistance. Int J Obes Relat Metab Disord 27 Suppl 3: S49–S52 Review

    PubMed  CAS  Google Scholar 

  • Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116(7):1793–1801 Review

    PubMed  CAS  Google Scholar 

  • Sooy K, Schermerhorn T, Noda M, Surana M, Rhoten WB, Meyer M, Fleischer N, Sharp GW, Christakos S (1999) Calbindin-D(28k) controls [Ca(2+)](i) and insulin release. Evidence obtained from calbindin-d(28k) knockout mice and beta cell lines. J Biol Chem 274(48):34343–34349

    PubMed  CAS  Google Scholar 

  • Spencer NF, Poynter ME, Im SY, Daynes RA (1997) Constitutive activation of NF-kappa B in an animal model of aging. Int Immunol 9(10):1581–1588

    PubMed  CAS  Google Scholar 

  • Spranger J, Kroke A, Mohlig M, Hoffmann K, Bergmann MM, Ristow M, Boeing H, Pfeiffer AF (2003) Inflammatory cytokines and the risk to develop type 2 diabetes: results of the prospective population-based European Prospective Investigation into Cancer and Nutrition (EPIC)— potsdam study. Diabetes 52(3):812–817

    PubMed  CAS  Google Scholar 

  • Stienstra R, Mandard S, Tan NS, Wahli W, Trautwein C, Richardson TA, Lichtenauer-Kaligis E, Kersten S, Muller M (2007) The Interleukin-1 receptor antagonist is a direct target gene of PPARalpha in liver J Hepatol 46(5):869–877

    PubMed  CAS  Google Scholar 

  • Storlien LH, Kraegen EW, Chisholm DJ, Ford GJ, Bruce DG, Pascoe SW (1987) Fish oil prevents insulin resistance induced by high-fat feeding in rats. Science 237:885–888

    PubMed  CAS  Google Scholar 

  • Takano H, Komuro I (2002) Roles of peroxisome proliferator-activated receptor gamma in cardiovascular disease. J Diabetes Complications 16:108–114

    PubMed  Google Scholar 

  • Tanaka T, Itoh H, Doi K, Fukunaga Y, Hosoda K, Shintani M, Yamashita J, Chun TH, Inoue M, Masatsugu K, Sawada N, Saito T, Inoue G, Nishimura H, Yoshimasa Y, Nakao K (1999) Down regulation of peroxisome proliferator-activated receptorgamma expression by inflammatory cytokines and its reversal by thiazolidinediones. Diabetologia 42(6):702–710

    PubMed  CAS  Google Scholar 

  • Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772–783 Review

    PubMed  CAS  Google Scholar 

  • Ulevitch RJ (2004) Therapeutics targeting the innate immune system. Nat Rev Immunol 512–520

    Google Scholar 

  • Van Den Biggelaar AH, Huizinga TW, de Craen AJ, Gussekloo J, Heijmans BT, Frolich M, Westendorp RG (2004) Impaired innate immunity predicts frailty in old age. The Leiden 85-plus study. Exp Gerontol 39(9):1407–1414

    PubMed  Google Scholar 

  • Venjatraman JT, Fernandes G (1997) Exercise, immunity and aging. Aging (Milano) 9(1–2):42–56 Review

    CAS  Google Scholar 

  • Von Knethen A, Brune B (2003) PPARgamma-an important regulator of monocyte/macrophage function. Arch Immunol Ther Exp 51:219–226

    Google Scholar 

  • Wei M, Schwertner HA, Blair SN (2000) The association between physical activity, physical fitness, and type 2 diabetes mellitus. Compr Ther 26(3):176–182 Review

    PubMed  CAS  Google Scholar 

  • Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr (2003) Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112(12):1796–1808

    PubMed  CAS  Google Scholar 

  • Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115(5): 1111– 1119 Review

    PubMed  CAS  Google Scholar 

  • Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112(12):1785–1788

    PubMed  CAS  Google Scholar 

  • Wikby A, Ferguson F, Forsey R, Thompson J, Strindhall J, Lofgren S, Nilsson BO, Ernerudh J, Pawelec G, Johansson B (2005) An immune risk phenotype, cognitive impairment, and survival in very late life: impact of allostatic load in Swedish octogenarian and nonagenarian humans. J Gerontol A Biol Sci Med Sci 60:556–565

    PubMed  Google Scholar 

  • Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen HJ (2003) Chronic inflammation in fat plays a crucial role in the development of obesityrelated insulin resistance. Clin Invest 112(12):1821–1830

    CAS  Google Scholar 

  • Zuany-Amorim C, Hastewell J, Walker C (2002) Toll-like receptors as potential therapeutic targets for multiple diseases. Nat Rev Drug Discov 1(10):797–807 Review

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Unilever Corporate Research, Sharnbrook, Bedfordshire, MK44 1LQ, United Kingdom

    Dawn J. Mazzatti, Kavita Karnik, Radu C. Oita & Jonathan R. Powell

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  1. Dawn J. Mazzatti
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  2. Kavita Karnik
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  3. Radu C. Oita
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  4. Jonathan R. Powell
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Editors and Affiliations

  1. Research Center on Aging, Department of Medicine, Immunology Graduate Programme, Faculty of Medicine, University of Sherbrooke, 1036 Rue Belvedere, J1H 4C4, Sherbrooke, Quebec, Canada

    Tamas Fulop

  2. Department of Experimental Pathalogy, CIG Interdepartmental Center “L. Galvani” University of Bologna, Via San Giacomo 12, 40126, Bologna, Italy

    Claudio Franceschi

  3. Institute for Health and Life Sciences, 4-6-22 Kohinato, Bunkyo-ku, Tokyo, 112-0006, Japan

    Katsuiku Hirokawa

  4. ZMF - Zentrum Med. Forschung Abt. Transplant./ Immunologie, University of Tübingen, Waldhörnlestr. 22, 72072, Tübingen, Germany

    Graham Pawelec

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Mazzatti, D.J., Karnik, K., Oita, R.C., Powell, J.R. (2009). Insulin Resistance, Chronic Inflammation and the Link with Immunosenescence. In: Fulop, T., Franceschi, C., Hirokawa, K., Pawelec, G. (eds) Handbook on Immunosenescence. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-9063-9_60

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