Insulin resistance, chronic inflammation and the link with immunosenescence

Handbook on Immunosenescence: Basic Understanding and Clinical Applications

Volumn 9781402090639, Issue , 2009, Pages 1247-1272

  Mazzatti, Dawn J ^a   Karnik, Kavita ^a   Oita, Radu C ^a   Powell, Jonathan R ^a  

^a UNILEVER RESEARCH   (United Kingdom)

Author keywords

Adipocytokines; Ageing; Frailty; I mmunosenescence; Inflammation; Insulin resistance

Indexed keywords

EID: 77953664967     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4020-9063-9_60     Document Type: Chapter

References (134)

1. 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
2. Auwerx J, Cock TA, Knouff C (2003) PPAR-gamma: a thrifty transcription factor. Nucl Recept Signal 1:e006
3. 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
4. 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
5. Berger J, Moller DE (2002) The mechanisms of action of ppars. Annu Rev Med 53:409-435
6. Blair SN, Wei M (2000) Sedentary habits, health, and function in older women and men. Am J Health Promot 15(1):1-8 Review
7. 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
8. 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
9. 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
10. 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
11. 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
12. 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
13. 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(5 S Suppl):1367S-1373S
14. 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
15. Browning LM (2003) n-3 Polyunsaturated fatty acids, inflammation and obesity-related disease. Proc Nutr Soc 62(2):447-453
16. 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
17. 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
18. 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
19. Calder PC (2005) Polyunsaturated fatty acids and inflammation. Biochem Soc Trans. 33(Pt 2):423-427 Review
20. Calle EE, Kaaks R (2004) Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer 4(8):579-591
21. 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
22. Chandra RK (2003) Nutrient regulation of immune functions. Forum Nutr 56:147-148 Review
23. 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
24. Cippitelli M, Santoni A (1998) Vitamin D3: a transcriptional modulator of the interferon-gamma gene. Eur J Immunol 28(10):3017-3030
25. Cohen HJ (1997) Cancer and the functional status of the elderly. Cancer 80(10):1883-1886
26. Cossarizza A, Ortolani C, Monti D, Franceschi C (1997) Cytometric analysis of immunosenescence. Cytometry 27(4):297-313 Review
27. 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
28. 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
29. 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
30. Devchand PR, Keller H, Peters JM, Vazquez M, Gonzalez FJ, Wahli W (1996) The PPARalphaleukotriene B4 pathway to inflammation control. Nature 384:39-43
31. 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
32. 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
33. Effros RB, Pawelec G (1997) Replicative senenscence of T lymphocytes: does the Hayflick limit lead to immune exhaustion? Immunol Today 18:450-454
34. 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
35. Estrach C, Abernethy VE, Dawson JK (2004) Infections and anti-TNF therapy: strategies for screening based on clinical experience. Rheumatology (Oxford) 43:115-116
36. 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
37. 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
38. 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
39. 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
40. 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
41. 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
42. 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
43. Ford ES (2002) Does exercise reduce inflammation? Physical activity and C-reactive protein among U. S. adults. Epidemiology 13(5):561-568
44. 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
45. 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
46. 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
47. 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
48. Gedik O, Akalin S (1986) Effects of vitamin D deficiency and repletion on insulin and glucagon secretion in man. Diabetologia 29(3):142-145
49. 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
50. 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
51. Ginaldi L, De Martinis M, Monti D, Franceschi C (2005) Chronic antigenic load and apoptosis in immunosenescence. Trends Immunol 26(2):79-84
52. 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
53. 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
54. 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
55. Hirosumi J, Tuncman G, Chang L et al. (2002) A central role for JNK in obesity and insulin resistance. Nature 420:333-336
56. 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
57. 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
58. 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
59. 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
60. Isaia G, Giorgino R, Adami S (2001) High prevalence of hypovitaminosis D in female type 2 diabetic population. Diabetes Care 24(8):1496
61. 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
62. Jiang C, Ting AT, Seed B (1998) PPAR-gamma agonists inhibit production of monocyte inflammatory cytokines. Nature 391:82-86
63. 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
64. 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
65. Kahn BB, Flier JS (2000) Obesity and insulin resistance. J Clin Invest 106(4):473-481 Review
66. 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
67. 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
68. 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
69. Kitano H, Oda K (2006) Robustness trade-offs and host-microbial symbiosis in the immune system. Mol Syst Biol doi:10.1038/msb4100039
70. 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
71. 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
72. La Cava A, Matarese G (2004) The weight of leptin in immunity. Nat Rev Immunol 4(5):371-379 Review
73. 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
74. 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
75. Lehmann JM, Lenhard JM, Oliver BB, Ringold GM, Kliewer SA (1997) Peroxisome proliferator-activated receptors α and γ are activated by indomethacin and other non-steroidal antiinflammatory drugs. J Biol Chem 272:3406-3410
76. 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
77. Lesourd B (1999) Immune response during disease and recovery in the elderly. Proc Nutr Soc 58(1):85-98 Review
78. 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
79. 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
80. 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
81. 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
82. Mandel MA, Mahmoud AA (1978) Impairment of cell-mediated immunity in mutation diabetic mice (db/db). J Immunol 120(4):1375-1377
83. 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
84. 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
85. 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):603-20
86. Mazzeo RS (1994) The influence of exercise and aging on immune function. Med Sci Sports Exerc 26(5):586-592 Review
87. Medzhitov R (2001) Toll-like receptors and innate immunity. Nat Rev Immunol 1(2):135-145 Review
88. 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
89. 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
90. 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
91. 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
92. 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
93. 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
94. 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
95. 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
96. Pawelec G, Hirokawa K, Fulop T (2001) Altered T cell signalling in ageing. Mech Ageing Dev 122:1613-1637
97. Pawelec G, Koch S, Griesemann H, Rehbein A, Hahnel K, Gouttefangeas C (2006) Immunosenescence, suppression and tumour progression. Cancer Immunol Immunother 55:981-986
98. Pawelec, G, Solana, R (1997) Immunosenescence. Immunol Today 18:514-516
99. 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
100. 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
101. 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]
102. 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
103. 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
104. 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
105. 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
106. 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
107. Rink L, Gabriel P (2001) Extracellular and immunological actions of zinc. Biometals 14:367-383
108. Rink L, Gabriel P (2000) Zinc and the immune system. Proc Nutr Soc 59:541-552
109. Rink L, Cakman I, Kirchner H (1998) Altered cytokine production in the elderly. Mech Ageing Dev 102(2-3):199-209 Review
110. 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
111. Shephard RJ, Shek PN (1995) Exercise, aging and immune function. Int J Sports Med 16(1):1-6 Review
112. 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
113. Shinkai S, Konishi M, Shephard RJ (1998) Aging and immune response to exercise. Can J Physiol Pharmacol 76(5):562-572 Review
114. 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
115. Shoelson SE, Lee J, Goldfine AB (2006) Inflammation and insulin resistance. J Clin Invest 116(7):1793-1801 Review
116. 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
117. Spencer NF, Poynter ME, Im S Y, Daynes RA (1997) Constitutive activation of NF-kappa B in an animal model of aging. Int Immunol 9(10):1581-1588
118. 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
119. 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
120. 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
121. Takano H, Komuro I (2002) Roles of peroxisome proliferator-activated receptor gamma in cardiovascular disease. J Diabetes Complications 16:108-114
122. 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
123. Tilg H, Moschen AR (2006) Adipocytokines: mediators linking adipose tissue, inflammation and immunity. Nat Rev Immunol 6(10):772-783 Review
124. Ulevitch RJ (2004) Therapeutics targeting the innate immune system. Nat Rev Immunol 512-520
125. 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
126. Venjatraman JT, Fernandes G (1997) Exercise, immunity and aging. Aging (Milano) 9(1-2):42-56 Review
127. Von Knethen A, Brune B (2003) PPARgamma-an important regulator of monocyte/macrophage function. Arch Immunol Ther Exp 51:219-226
128. 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
129. 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
130. Wellen KE, Hotamisligil GS (2005) Inflammation, stress, and diabetes. J Clin Invest 115(5):1111-1119 Review
131. Wellen KE, Hotamisligil GS (2003) Obesity-induced inflammatory changes in adipose tissue. J Clin Invest 112(12):1785-1788
132. 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
133. 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
134. 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