Aging is a biological process characterized by time-dependent functional declines that are influenced by changes in redox status and by oxidative stress-induced inflammatory reactions. An organism’s pro-inflammatory status may underlie the aging process and age-related diseases. In this review, we explore the molecular basis of low-grade, unresolved, subclinical inflammation as a major risk factor for exacerbating the aging process and age-related diseases. We focus on the redox-sensitive transcription factors, NF-κB and FOXO, which play essential roles in the expression of pro-inflammatory mediators and anti-oxidant enzymes, respectively. Major players in molecular inflammation are discussed with respect to the age-related up-regulation of pro-inflammatory cytokines and adhesion molecules, cyclo-oxygenase-2, lipoxygenase, and inducible nitric oxide synthase. The molecular inflammation hypothesis proposed by our laboratory is briefly described to give further molecular insights into the intricate interplay among redox balance, pro-inflammatory gene activation, and chronic age-related inflammatory diseases. The final section discusses calorie restriction as an aging-retarding intervention that also exhibits extraordinarily effective anti-inflammatory activity by modulating GSH redox, NF-κB, SIRT1, PPARs, and FOXOs.
Accili D,Arden KC.FOXOS at the crossroads of cellular metabolism, differentiation, and transformation.Cell. 2004;117:421-426
2.
Bäck M,Hlawaty H,Labat C,Michel JB,Brink C.The oral cavity and age: a site of chronic inflammation?.PLoS One. 2007;2:e135
3.
Baek BS,Kwon HJ,Lee KH,Yoo MA,Kim KW,Ikeno Y, et al.Regional difference of ROS generation, lipid peroxidation and anti-oxidant enzyme activity in rat brain and their dietary modulation.Arch Pharm Res. 1999;22:361-366
4.
Baldwin AS.The NF-kappa B and I kappa B proteins: new discoveries and insights.Annu Rev Immunol. 1996;14:649-683
5.
Bartke A.Insulin and aging.Cell Cycle. 2008;7:3338-3334
6.
Boskey A,Coleman R.Aging and bone.J Dent Res. 2010;89:1333-1348
7.
Bouallegue A,Vardatsikos G,Srivastava AK.Role of insulin-like growth factor 1 receptor and c-Src in endothelin-1- and angiotensin II-induced PKB phosphorylation, and hypertrophic and proliferative responses in vascular smooth muscle cells.Can J Physiol Pharmacol. 2009;87:1009-1018
8.
Breese CR,Ingram RL,Sonntag WE.Influence of age and long-term dietary restriction on plasma insulin-like growth factor-1 (IGF-1), IGF-1 gene expression, and IGF-1 binding proteins.J Gerontol. 1991;46:B180-B187
9.
Bruunsgaard H,Andersen-Ranberg K,Jeune B,Pedersen AN,Skinhøj P,Pedersen BK.A high plasma concentration of TNF-alpha is associated with dementia in centenarians.J Gerontol A Biol Sci Med Sci. 1999;54:M357-M364
10.
Bruunsgaard H,Andersen-Ranberg K,Hjelmborg JB,Pedersen BK,Jeune B.Elevated levels of tumor necrosis factor alpha and mortality in centenarians.Am J Med. 2003a;115:278-283
11.
Bruunsgaard H,Ladelund S,Pedersen AN,Schroll M,Jørgensen T,Pedersen BK.Predicting death from tumour necrosis factor-alpha and interleukin-6 in 80-year-old people.Clin Exp Immunol. 2003b;132:24-31
12.
Bullon P,Morillo JM,Ramirez-Tortosa MC,Quiles JL,Newman HN,Battino M.Metabolic syndrome and periodontitis: is oxidative stress a common link?.J Dent Res. 2009a;88:503-518
13.
Bullon P,Quiles JL,Morillo JM,Rubini C,Goteri G,Granados-Principal S, et al.Gingival vascular damage in atherosclerotic rabbits: hydroxytyrosol and squalene benefits.Food Chem Toxicol. 2009b;47:2327-2331
14.
Burgering BM,Medema RH.Decisions on life and death: FOXO Forkhead transcription factors are in command when PKB/Akt is off duty.J Leukoc Biol. 2003;73:689-701
15.
Byrne CD.Fatty liver: role of inflammation and fatty acid nutrition.Prostaglandins Leukot Essent Fatty Acids. 2010;82:265-271
16.
Cai D,Yuan M,Frantz DF,Melendez PA,Hansen L,Lee J, et al.Local and systemic insulin resistance resulting from hepatic activation of IKK-beta and NF-kappaB.Nat Med. 2005;11:183-190
17.
Cantó C,Auwerx J.Caloric restriction, SIRT1 and longevity.Trends Endocrinol Metab. 2009;20:325-331
18.
Carter CS,Hofer T,Seo AY,Leeuwenburgh C.Molecular mechanisms of life- and health-span extension: role of calorie restriction and exercise intervention.Appl Physiol Nutr Metab. 2007;32:954-966
19.
Cartier A,Côté M,Lemieux I,Pérusse L,Tremblay A,Bouchard C, et al.Age-related differences in inflammatory markers in men: contribution of visceral adiposity.Metabolism. 2009;58:1452-1458
20.
Cesari M,Penninx BW,Pahor M,Lauretani F,Corsi AM,Rhys Williams G, et al.Inflammatory markers and physical performance in older persons: the InCHIANTI study.J Gerontol A Biol Sci Med Sci. 2004;59:242-248
21.
Chapple IL.Potential mechanisms underpinning the nutritional modulation of periodontal inflammation.J Am Dent Assoc. 2009;140:178-184
22.
Chapple IL,Matthews JB.The role of reactive oxygen and antioxidant species in periodontal tissue destruction.Periodontol 2000. 2007;43:160-232
23.
Chapple IL,Milward MR,Dietrich T.The prevalence of inflammatory periodontitis is negatively associated with serum antioxidant concentrations.J Nutr. 2007;137:657-664
24.
Chinetti G,Fruchart JC,Staels B.Peroxisome proliferator-activated receptors (PPARs): nuclear receptors at the crossroads between lipid metabolism and inflammation.Inflamm Res. 2000;49:497-505
25.
Chiribau CB,Cheng L,Cucoranu IC,Yu YS,Clempus RE,Sorescu D.FOX03A regulates peroxiredoxin III expression in human cardiac fibroblasts.J Biol Chem. 2008;283:8211-8217
26.
Cho CG,Kim HJ,Chung SW,Jung KJ,Shim KH,Yu BP, et al.Modulation of glutathione and thioredoxin systems by calorie restriction during the aging process.Exp Gerontol. 2003;38:539-548
27.
Choi JH,Yu BP.Dietary restriction as a modulator of age-related changes in rat kidney prostaglandin production.J Nutr Health Aging. 1998;2:167-171
28.
Chung HY,Kim HJ,Shim KH,Kim KW.Dietary modulation of prostanoid synthesis in the aging process: role of cyclooxygenase-2.Mech Ageing Dev. 1999;111:97-106
29.
Chung HY,Kim HJ,Kim JW,Yu BP.The inflammation hypothesis of aging: molecular modulation by calorie restriction.Ann NY Acad Sci. 2001;928:327-335
30.
Chung HY,Kim HJ,Kim KW,Choi JS,Yu BP.Molecular inflammation hypothesis of aging based on the anti-aging mechanism of calorie restriction.Microsc Res Tech. 2002;59:264-272
31.
Chung HY,Sung B,Jung KJ,Zou Y,Yu BP.The molecular inflammatory process in aging.Antioxid Redox Signal. 2006;8:572-581
32.
Chung HY,Cesari M,Anton S,Marzetti E,Giovannini S,Seo AY, et al.Molecular inflammation: underpinnings of aging and age-related diseases.Ageing Res Rev. 2009;8:18-30
33.
Cochran DL.Inflammation and bone loss in periodontal diseases.J Periodontol. 2008;79 (8 Suppl): 1569S-1576S
34.
Cohen HY,Miller C,Bitterman KJ,Wall NR,Hekking B,Kessler B, et al.Calorie restriction promotes mammalian cell survival by inducing the SIRT1 deacetylase.Science. 2004;305:390-392
35.
Cross CE,Hasegawa G,Reddy KA,Omaye ST.Enhanced lung toxicity of 02 in selenium-deficient rats.Res Commun Chem Pathol Pharmacol. 1977;16:695-706
36.
Csiszar A,Wang M,Lakatta EG,Ungvari Z.Inflammation and endothelial dysfunction during aging: role of NF-kappaB.J Appl Physiol. 2008;105:1333-1341
37.
Del Fattore A,Cappariello A,Teti A.Genetics, pathogenesis and complications of osteopetrosis.Bone. 2008;42:19-29
38.
Devaux B,Scholz D,Hirche A,Klovekorn WP,Schaper J.Upregulation of cell adhesion molecules and the presence of low grade inflammation in human chronic heart failure.Eur Heart J. 1997;18:470-479
Feige JN,Auwerx J.Transcriptional targets of sirtuins in the coordination of mammalian physiology.Curr Opin Cell Biol. 2008;20:303-309
41.
Feng L,Xia Y,Garcia GE,Hwang D,Wilson CB.Involvement of reactive oxygen intermediates in cyclooxygenase-2 expression induced by interleukin-1 tumor necrosis factor-alpha and lipopolysaccharide.J Clin Invest. 1995;95:1669-1675
42.
Filiopoulos V,Vlassopoulos D.Inflammatory syndrome in chronic kidney disease: pathogenesis and influence on outcomes.Inflamm Allergy Drug Targets. 2009;8:369-382
43.
Fisher GJ,Datta SC,Talwar HS,Wang ZQ,Varani J,Kang S, et al.Molecular basis of sun-induced premature skin ageing and retinoid antagonism.Nature. 1996;379:335-339
44.
Franceschi C.Inflammaging as a major characteristic of old people: can it be prevented or cured?.Nutr Rev. 2007;65 (12 Pt 2): S173-S176
45.
Frescas D,Valenti L,Accili D.Nuclear trapping of the forkhead transcription factor Fox01 via Sirt-dependent deacetylation promotes expression of glucogenetic genes.J Biol Chem. 2005;280:20589-20595
46.
Funaki M.Saturated fatty acids and insulin resistance.J Med Invest. 2009;56:88-92
47.
Furugen R,Hayashida H,Yamaguchi N,Yoshihara A,Ogawa H,Miyazaki H, et al.The relationship between periodontal condition and serum levels of resistin and adiponectin in elderly Japanese.J Clin Periodontol. 2008;43:556-562
48.
Galgani JE,Uauy RD,Aguirre CA,Díaz EO.Effect of the dietary fat quality on insulin sensitivity.Br J Nutr. 2008;100:471-479
49.
Galkina E,Ley K.Immune and inflammatory mechanisms of atherosclerosis.Annu Rev Immunol. 2009;27:165-197
50.
Gangemi S,Pescara L,D’Urbano E,Basile G,Nicita-Mauro V,Davì G, et al.Aging is characterized by a profound reduction in anti-inflammatory lipoxin A4 level.Exp Gerontol. 2005;40:612-614
Goldberg RB.Cytokine and cytokine-like inflammation markers, endothelial dysfunction, and imbalanced coagulation in development of diabetes and its complications.J Clin Endocrinol Metab. 2009;94:3171-3182
55.
Handel ML,McMorrow LB,Gravallese EM.Nuclear factor-kappa B in rheumatoid synovium. Localization of p50 and p65.Arthritis Rheum. 1995;38:1762-1770
56.
Havens AM,Chiu E,Taba M,Wang J,Shiozawa Y,Jung Y, et al.Stromal-derived factor-1alpha (CXCL12) levels increase in periodontal disease.J Periodontol. 2008;79:845-853
57.
Hayashi H,Yamaza H,Komatsu T,Park S,Chiba T,Higami Y, et al.Calorie restriction minimizes activation of insulin signaling in response to glucose: potential involvement of the growth hormone-insulin-like growth factor 1 axis.Exp Gerontol. 2008;43:827-832
58.
Hedrick SM.The cunning little vixen: Foxo and the cycle of life and death.Nat Immunol. 2009;10:1057-1063
59.
Helenius M,Hanninen M,Lehtinen SK,Salminen A.Aging induced up-regulation of nuclear binding activities of oxidative stress responsive NF-KB transcription factor in mouse cardiac muscle.J Mol Cell Cardiol. 1996;28:487-498
60.
Herrera MD,Mingorance C,Rodríguez-Rodríguez R,Alvarez de Sotomayor M.Endothelial dysfunction and aging: an update.Ageing Res Rev. 2010;9:142-152
61.
Hewitt C,McCormick D,Linden G,Turk D,Stern I,Wallace I, et al.The role of cathepsin C in Papillon-Lefèvre syndrome, prepubertal periodontitis, and aggressive periodontitis.Hum Mutat. 2004;23:222-228
62.
Heydari AR,Richardson A.Does gene expression play any role in the mechanism of the antiaging effect of dietary restriction?.Ann NY Acad Sci. 1992;663:384-395
Hotamisligil GS.Endoplasmic reticulum stress and the inflammatory basis of metabolic disease.Cell. 2010;140:900-917
65.
Huttner EA,Machado DC,de Oliveira RB,Antunes AG,Hebling E.Effects of human aging on periodontal tissues.Spec Care Dentist. 2009;29:149-155
66.
Jung KJ,Lee EK,Yu BP,Chung HY.Significance of protein tyrosine kinase/protein tyrosine phosphatase balance in the regulation of NF-kappaB signaling in the inflammatory process and aging.Free Radic Biol Med. 2009a;47:983-991
67.
Jung KJ,Lee EK,Kim JY,Zou Y,Sung B,Heo HS, et al.Effect of short term calorie restriction on pro-inflammatory NF-κB and AP-1 in aged rat kidney.Inflamm Res. 2009b;58:143-150
68.
Kahn BB,Flier JS.Obesity and insulin resistance.J Clin Invest. 2000;106:473-481
69.
Karthikeyan BV,Pradeep AR.Gingival crevicular fluid and serum leptin: their relationship to periodontal health and disease.J Clin Periodontol. 2007;34:467-472
70.
Kim DH,Kim JY,Yu BP,Chung HY.The activation of NF-κB through Akt-induced FOX01 phosphorylation during aging and its modulation by calorie restriction.Biogerontology. 2008;9:33-47
71.
Kim HJ,Kim KW,Yu BP,Chung HY.The effect of age on cyclooxygenases-2 gene expression: NF-kappaB activation and IkappaBalpha degradation.Free Radic Biol Med. 2000;28:683-692
72.
Kim HJ,Jung KJ,Yu BP,Cho CG,Choi JS,Chung HY.Modulation of redox-sensitive transcription factors by calorie restriction during aging.Mech Ageing Dev. 2002;123:1589-1595
73.
Kim HK,Park HR,Sul KH,Chung HY,Chung J.Induction of RANTES and CCR5 through NF-kappaB activation via MAPK pathway in aged rat gingival tissues.Biotechnol Lett. 2006;28:17-23
74.
Kim HK,Park HR,Lee JS,Chung TS,Chung HY,Chung J.Down-regulation of iNOS and TNF-alpha expression by kaempferol via NF-kappaB inactivation in aged rat gingival tissues.Biogerontology. 2007;8:399-408
75.
Kim JW,Baek BS,Kim YK,Herlihy JT,Ikeno Y,Yu BP, et al.Gene expression of cyclooxygenase in the aging heart.J Gerontol A Biol Sci Med Sci. 2001;56:B350-355
76.
Kim KS,Kang KW,Seu YB,Baek SH,Kim JR.Interferon-gamma induces cellular senescence through p53-dependent DNA damage signaling in human endothelial cells.Mech Ageing Dev. 2009;130:179-188
77.
Kirkwood KL,Rossa C.The potential of p38 MAPK inhibitors to modulate periodontal infections.Curr Drug Metab. 2009;10:55-67
78.
Kobayashi Y,Furukawa-Hibi Y,Chen C,Horio Y,Isobe K,Ikeda K, et al.SIRT1 is critical regulator of FOXO-mediated transcription in response to oxidative stress.Int J Mol Med. 2005;16:237-243
79.
Kops GJ,Dansen TB,Polderman PE,Saarloos I,Wirtz KW,Coffer PJ, et al.Forkhead transcription factor FOX03a protects quiescent cells from oxidative stress.Nature. 2002;419:316-321
80.
Korhonen P,Helenius M,Salminen A.Age-related changes in the regulation of NF-kappa B in rat brain.Neurosci Lett. 1997;225:61-64
81.
Krabbe KS,Pedersen M,Bruunsgaard H.Inflammatory mediators in the elderly.Exp Gerontol. 2004;39:687-699
82.
Kritchevsky SB,Cesari M,Pahor M.Inflammatory markers and cardiovascular health in older adults.Cardiovasc Res. 2005;66:265-275
83.
Lawlor MA,Alessi DR.PKB/Akt: a key mediator of cell proliferation, survival and insulin responses?.J Cell Sci. 2001;114 (Pt 16): 2903-2910
84.
Lerner U.Inflammation-induced bone remodeling in periodontal disease and the influence of post-menopausal osteoporosis.J Dent Res. 2006;85:596-607
85.
Li Z,Froehlich J,Galis ZS,Lakatta EG.Increased expression of matrix metalloproteinase-2 in the thickened intima of aged rats.Hypertension. 1999;33:116-123
86.
Liang S,Hosur KB,Domon H,Hajishengallis G.Periodontal inflammation and bone loss in aged mice.J Periodontal Res. 2010;45:574-578
87.
Liu SL,Lin X,Shi DY,Cheng J,Wu CQ,Zhang YD.Reactive oxygen species stimulated human hepatoma cell proliferation via cross-talk between PI3-K/PKB and JNK signaling pathways.Arch Biochem Biophys. 2002;406:173-182
88.
Lu L,Liu H,Peng J,Gan L,Shen L,Zhang Q, et al.Regulations of the key mediators in inflammation and atherosclerosis by aspirin in human macrophages.Lipids Health Dis. 2010;9:16
89.
Lykkesfeldt J,Hagen TM,Vinarsky V,Ames BN.Age-associated decline in ascorbic acid concentration, recycling, and biosynthesis in rat hepatocytes—reversal with (R)-alpha-lipoic acid supplementation.FASEB J. 1998;12:1183-1189
90.
Maggio M,Guralnik JM,Longo DL,Ferrucci L.Interleukin-6 in aging and chronic disease: a magnificent pathway.J Gerontol A Biol Sci Med Sci. 2006;61:575-584
91.
Mahmud DL,G-Amlak M,Deb DK,Platanias LC,Uddin S,Wickrema A.Phosphorylation of forkhead transcription factors by erythropoietin and stem cell factor prevents acetylation and their interaction with coactivator p300 in erythroid progenitor cells.Oncogene. 2002;21:1556-1562
92.
Marinkovic D,Zhang X,Yalcin S,Luciano JP,Brugnara C,Huber T, et al.Fox03 is required for the regulation of oxidative stress in erythropoiesis.J Clin Invest. 2007;117:2133-2144
93.
Martelli-Junior H,Cotrim P,Graner E,Sauk JJ,Coletta RD.Effect of transforming growth factor-beta1, interleukin-6, and interferon-gamma on the expression of type I collagen, heat shock protein 47, matrix metalloproteinase (MMP)-1 and MMP-2 by fibroblasts from normal gingiva and hereditary gingival fibromatosis.J Periodontol. 2003;74:296-306
94.
Masternak MM,Bartke A.PPARs in calorie restricted and genetically long-lived mice.PPAR Res. 2007;2007:28436
95.
Matthews JB,Wright HJ,Roberts A,Cooper PR,Chapple IL.Hyperactivity and reactivity of peripheral blood neutrophils in chronic periodontitis.Clin Exp Immunol. 2007a;147:255-264
McCay CM,Crowell MF,Maynard LA.The effect of retarded growth upon the length of life span upon the ultimate body size.J Nutrition. 1935;10:63-79
98.
McCormick RK.Osteoporosis: integrating biomarkers and other diagnostic correlates into the management of bone fragility.Altern Med Rev. 2007;12:113-145
99.
McLean RR.Proinflammatory cytokines and osteoporosis.Curr Osteoporos Rep. 2009;7:134-139
100.
Mura CV,Gong X,Taylor A,Villalobos-Molina R,Scrofano MM.Effects of calorie restriction and aging on the expression of antioxidant enzymes and ubiquitin in the liver of Emory mice.Mech Ageing Dev. 1996;91:115-129
Nasrin N,Ogg S,Cahill CM,Biggs W,Nui S,Dore J, et al.DAF-16 recruits the CREB-binding protein coactivator complex to the insulin-like growth factor binding protein 1 promoter in HepG2 cells.Proc Natl Acad Sci USA. 2000;97:10412-10417
Nesbitt MJ,Reynolds MA,Shiau H,Choe K,Simonsick EM,Ferrucci L.Association of periodontitis and metabolic syndrome in the Baltimore Longitudinal Study of Aging.Aging Clin Exp Res. 2010;22:238-242
105.
Nishimura F,Murayama Y.Periodontal inflammation and insulin resistance—lessons from obesity.J Dent Res. 2001;80:1690-1694
106.
Nisoli E,Tonello C,Cardile A,Cozzi V,Bracale R,Tedesco L, et al.Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS.Science. 2005;310:314-317
107.
Parkkila S,Innocenti A,Kallio H,Hilvo M,Scozzafava A,Supuran CT.The protein tyrosine kinase inhibitors imatinib and nilotinib strongly inhibit several mammalian alpha-carbonic anhydrase isoforms.Bioorg Med Chem Lett. 2009;19:4102-4106
108.
Picard F,Kurtev M,Chung N,Topark-Ngarm A,Senawong T,Machado de Oliveira R, et al.Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-gamma.Nature. 2004;429:771-776
Polyzos SA,Kountouras J,Zavos C.Nonalcoholic fatty liver disease: the pathogenetic roles of insulin resistance and adipocytokines.Curr Mol Med. 2009;9:299-314
111.
Puigserver P,Rhee J,Donovan J,Walkey CJ,Yoon JC,Oriente F, et al.Insulin-regulated hepatic gluconeogenesis through FOX01-PGC-1alpha interaction.Nature. 2003;423:550-555
112.
Ramirez-Tortosa MC,Quiles JL,Battino M,Granados S,Morillo JM,Bompadre S, et al.Periodontitis is associated with altered plasma fatty acids and cardiovascular risk markers.Nutr Metab Cardiovasc Dis. 2010;20:133-139
113.
Ridker PM.Inflammation, infection, and cardiovascular risk: how good is the clinical evidence?.Circulation. 1998;97:1671-1674
114.
Ridker PM,Stampfer MJ,Rifai N.Novel risk factors for systemic atherosclerosis: a comparison of C-reactive protein, fibrinogen, homocysteine, lipoprotein(a), and standard cholesterol screening as predictors of peripheral arterial disease.J Am Med Assoc. 2001;285:2481-2485
115.
Rikans LE,DeCicco LA,Hornbrook KR,Yamano T.Effect of age and carbon tetrachloride on cytokine concentrations in rat liver.Mech Ageing Dev. 1999;108:173-182
116.
Roth GS,Ingram DK,Joseph JA.Nutritional interventions in aging and age-associated diseases.Ann NY Acad Sci. 2007;1114:369-371
117.
Roubenoff R,Harris TB,Abad LW,Wilson PW,Dallal GE,Dinarello CA.Monocyte cytokine production in an elderly population: effect of age and inflammation.J Gerontol A Biol Sci Med Sci. 1998;53:M20-M26
118.
Salih DA,Brunet A.FoxO transcription factors in the maintenance of cellular homeostasis during aging.Curr Opin Cell Biol. 2008;20:126-136
119.
Salminen A,Kaarniranta K.Genetics vs entropy: longevity factors suppress the NF-κB-driven entropic aging process.Ageing Res Rev. 2010;9:298-314
120.
Sansoni P,Vescovini R,Fagnoni F,Biasini C,Zanni F,Zanlari L, et al.The immune system in extreme longevity.Exp Gerontol. 2008;43:61-65
121.
Saraiva M,O’Garra A.The regulation of IL-10 production by immune cells.Nat Rev Immunol. 2010;10:170-181
122.
Sarsour EH,Kumar MG,Chaudhuri L,Kalen AL,Goswami PC.Redox control of the cell cycle in health and disease.Antioxid Redox Signal. 2009;11:2985-3011
123.
Serhan CN.Resolution phase of inflammation: novel endogenous anti-inflammatory and proresolving lipid mediators and pathways.AnnuRev Immunol. 2007;25:101-137
124.
Shimizu H,Nakagami H,Morita S,Tsukamoto I,Osako MK,Nakagami F, et al.New treatment of periodontal diseases by using NF-κB decoy oligodeoxynucleotides via prevention of bone resorption and promotion of wound healing.Antioxid Redox Signal. 2009;11:2065-2075
125.
Sinclair DA,Guarente L.Extrachromosomal rDNA circles—a cause of aging in yeast.Cell. 1997;91:1033-1042
126.
Suganami T,Ogawa Y.Adipose tissue macrophages: their role in adipose tissue remodeling.J Leukoc Biol. 2010;88:33-39
127.
Sung B,Park S,Yu BP,Chung HY.Modulation of PPAR in aging, inflammation, and calorie restriction.J Gerontol A Biol Sci Med Sci. 2004;59:997-1006
128.
Sung B,Park S,Yu BP,Chung HY.Amelioration of age-related inflammation and oxidative stress by PPARgamma activator: suppression NF-kappaB by 2,4-thiazolidinedione.Exp Gerontol. 2006;41:590-599
129.
Tardif F,Ross G,Rouabhia M.Gingival and dermal fibroblasts produce interleukin-1 beta converting enzyme and interleukin-1 beta but not interleukin-18 even after stimulation with lipopolysaccharide.J Cell Physiol. 2004;198:125-132
130.
Tereshina EV.Metabolic abnormalities as a basis for age-dependent diseases and aging? State of the art.Adv Gerontol. 2009;22:129-138
131.
Ungvari Z,Orosz Z,Labinskyy N,Rivera A,Xiangmin Z,Smith K, et al.Increased mitochondrial H2O2 production promotes endothelial NF-κB activation in aged rat arteries.Am J Physiol Heart Circ Physiol. 2007;293:H37-H47
132.
Van der Heide LP,Hoekman MF,Smidt MP.The ins and outs of FoxO shuttling: mechanisms of FoxO translocation and transcriptional regulation.Biochem J. 2004;380 (Pt 2): 297-309
133.
Wahli W.Peroxisome proliferator-activated receptors (PPARs): from metabolic control to epidermal wound healing.Swiss Med Wkly. 2002;132:83-91
134.
Willette AA,Bendlin BB,McLaren DG,Canu E,Kastman EK,Kosmatka KJ, et al.Age-related changes in neural volume and microstructure associated with interleukin-6 are ameliorated by a calorie-restricted diet in old rhesus monkeys.Neuroimage. 2010;51:987-994
135.
Williams R,Offenbacher S.Periodontal medicine: the emergence of a new branch of periodontology.Periodontol. 2000;23:9-12
136.
Xu J,Wu HF,Ang ES,Yip K,Woloszyn M,Zheng MH, et al.NF-kappaB modulators in osteolytic bone diseases.Cytokine Growth Factor Rev. 2009;20:7-17
137.
Yamaguchi N,Kukita T,Li YJ,Martinez Argueta JG,Saito T,Hanazawa S, et al.Adiponectin inhibits osteoclast formation stimulated by lipopolysaccharide from Actinobacillus actinomycetemcomitans.FEMS Immunol Med Microbiol. 2007;49:28-34
138.
Yeung F,Hoberg JE,Ramsey CS,Keller MD,Jones DR,Frye RA, et al.Modulation of NFkappaB-dependent transcription and cell survival by the SIRT1 deacetylase.EMBO J. 2004;23:2369-2380
139.
Yu BP.Aging and oxidative stress: modulation by dietary restriction.Free Radic Biol Med. 1996;21:651-668
140.
Yu BP.Why calorie restriction would work for human longevity.Biogerontology. 2006;7:179-182
141.
Yu BP,Chung HY.Oxidative stress and vascular aging.Diabetes Res Clin Pract. 2001;54 (Suppl 2): 73-80
142.
Yu BP,Chung HY.Adaptive mechanisms to oxidative stress during aging.Mech Ageing Dev. 2006;127:436-443
143.
Zou Y,Jung KJ,Kim JW,Yu BP,Chung HY.Alteration of soluble adhesion molecules during aging and their modulation by calorie restriction.FASEB J. 2004;18:320-322
144.
Zou Y,Kim DH,Jung KJ,Heo HS,Kim CH,Baik HS, et al.Lysophosphatidylcholine enhances oxidative stress via the 5-lipoxygenase pathway in rat aorta during aging.Rejuvenation Res. 2009;12:15-24
