Please wait a minute...
 Home  About the Journal Editorial Board Aims & Scope Peer Review Policy Subscription Contact us
Early Edition  //  Current Issue  //  Open Special Issues  //  Archives  //  Most Read  //  Most Downloaded  //  Most Cited
Aging and Disease    2015, Vol. 6 Issue (2) : 109-120     DOI: 10.14336/AD.2014.0305
Review Article |
Metabolic Syndrome, Aging and Involvement of Oxidative Stress
Francesca Bonomini(),Luigi Fabrizio Rodella,Rita Rezzani
Division of Anatomy and Physiopathology, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy
Download: PDF(571 KB)   HTML
Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks    

The prevalence of the metabolic syndrome, a cluster of cardiovascular risk factors associated with obesity and insulin resistance, is dramatically increasing in Western and developing countries. This disorder consists of a cluster of metabolic conditions, such as hypertriglyceridemia, hyper-low-density lipoproteins, hypo-high-density lipoproteins, insulin resistance, abnormal glucose tolerance and hypertension, that-in combination with genetic susceptibility and abdominal obesity-are risk factors for type 2 diabetes, vascular inflammation, atherosclerosis, and renal, liver and heart diseases. One of the defects in metabolic syndrome and its associated diseases is excess of reactive oxygen species. Reactive oxygen species generated by mitochondria, or from other sites within or outside the cell, cause damage to mitochondrial components and initiate degradative processes. Such toxic reactions contribute significantly to the aging process. In this article we review current understandings of oxidative stress in metabolic syndrome related disease and its possible contribution to accelerated senescence.

Keywords metabolic syndrome      aging      accelerated senescence      oxidative stress     
Corresponding Authors: Francesca Bonomini     E-mail:
Just Accepted Date: 25 November 2014   Online First Date: 23 November 2014    Issue Date: 25 March 2015
E-mail this article
E-mail Alert
Articles by authors
Francesca Bonomini
Luigi Fabrizio Rodella
Rita Rezzani
Cite this article:   
Francesca Bonomini,Luigi Fabrizio Rodella,Rita Rezzani. Metabolic Syndrome, Aging and Involvement of Oxidative Stress[J]. A&D, 2015, 6(2): 109-120.
URL:     OR
Figure 1.  Schematic relationship between ROS production, accelerated senescence and metabolic syndrome.
[1] Humphreys MH (2011). The brain splits obesity and hypertension. Nat Med, 17:782–3.
[2] Kahn SE,Hull RL,Utzschneider KM (2006). Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature, 444: 840–6.
[3] Giovannucci E,Michaud D (2007). The role of obesity and related metabolic disturbances in cancers of the colon, prostate, and pancreas. Gastroenterology, 132:2208–25.
[4] Parekh S,Anania FA (2007). Abnormal lipid and glucose metabolism in obesity: implications for nonalcoholic fatty liver disease. Gastroenterology, 132:2191–207.
[5] Bamba V,Rader DJ (2007). Obesity and atherogenic dyslipidemia. Gastroenterology, 132:2181–90.
[6] Van Gaal LF,Mertens IL,De Block CE (2006). Mechanisms linking obesity with cardiovascular disease. Nature, 444:875–80.
[7] Semenkovich CF (2006). Insulin resistance and atherosclerosis. J Clin Invest, 116:1813–22.
[8] Friedman JM (2009). Obesity: Causes and control of excess body fat. Nature, 459:340–2.
[9] Ogden CL,Yanovski SZ,Carroll MD,Flegal KM (2007). The epidemiology of obesity. Gastroenterology, 132:2087–102.
[10] Yoon KH,Lee JH,Kim JW,Cho JH,Choi YH,Ko SH (2006). Epidemic obesity and type 2 diabetes in Asia. Lancet, 368:1681–8.
[11] Abelson P,Kennedy D (2004). The obesity epidemic. Science, 304:1413.
[12] Zimmet P,Alberti KG,Shaw J (2001). Global and societal implications of the diabetes epidemic. Nature, 414:782–7.
[13] Despres JP,Lemieux I (2006). Abdominal obesity and metabolic syndrome. Nature, 444:881–7.
[14] Eckel RH,Grundy SM,Zimmet PZ (2005). The metabolic syndrome. Lancet, 365:1415–28.
[15] Guarente L (2006). Sirtuins as potential targets for metabolic syndrome. Nature, 444:868–74.
[16] Duvnjak L,Duvnjak M (2009). The metabolic syndrome - an ongoing story. J. Physiol. Pharmacol, 60(Suppl 7):19–24.
[17] Gaddam KK,Ventura HO,Lavie CJ (2011). Metabolic syndrome and heart failure-the risk, paradox, and treatment. Curr Hypertens Rep, 13:142–8.
[18] Rodriguez A,Muller DC,Metter EJ,Maggio M,Harman SM,Blackman MR (2007). Aging, androgens, and the metabolic syndrome in a longitudinal study of aging. J Clin Endocrinol Metab, 92:3568–72.
[19] Moulana M,Lima R,Reckelhoff JF (2011). Metabolic syndrome, androgens, and hypertension. Curr Hypertens Rep, 13:158–62.
[20] Cai D,Liu T (2012). Inflammatory cause of metabolic syndrome via brain stress and NF-κB. Aging (Albany NY), 4(2):98–115.
[21] Wilson PW,D’Agostino RB,Parise H,Sullivan L,Meigs JB (2005). Metabolic syndrome as a precursor of cardiovascular disease and type 2 diabetes mellitus. Circulation, 112:3066–72.
[22] Katzmaryk PT,Leon AS,Wilmore JH,Skinner JS,Rao DC,Rankinen T, (2003). Targeting the metabolic syndrome with exercise: evidence from the heritage family study. Medial Sci Sports Exerc, 35(10):1703–9.
[23] Fauci AS (2008). Harrison’s principles of internal medicine. McGraw-Hill Medical. ISBN 0-07-147692-X.
[24] Grundy SM,Cleeman JI,Daniels SR,Donato KA,Eckel RH,Franklin BA,Gordon DJ,Krauss RM,Savage PJ,Smith SCJr,Spertus JA,Costa F; American Heart Association; National Heart, Lung, and Blood Institute (2005) Diagnosis and management of the metabolic syndrome: an American Heart Association/National Heart, Lung, and Blood Institute Scientific Statement. Circulation, 112: 2735–2752.
[25] Borch-Johnsen K,Wareham N (2010). The rise and fall of the metabolic syndrome. Diabetologia, 53: 597–599.
[26] Guize L,Thomas F,Pannier B,Bean K,Jego B,Benetos A (2007). All-cause mortality associated with specific combinations of the metabolic syndrome according to recent definitions. Diabetes Care, 30: 2381–2387.
[27] Zambon S,Zanoni S,Romanato G,Corti MC,Noale M,Sartori L (2009). Metabolic syndrome and all-cause and cardiovascular mortality in an Italian elderly population: the Progetto Veneto Anziani (Pro.V.A.) study. Diabetes Care, 32:153–159.
[28] Nunn AV,Bell JD,Guy GW (2009) Lifestyle-induced metabolic inflexibility and accelerated ageing syndrome: insulin resistance, friend or foe?. Nutr Metab (Lond.), 6: 16.
[29] Haffner S,Taegtmeyer H (2003) Epidemic obesity and the metabolic syndrome. Circulation, 108: 1541–1545.
[30] Harman D (1956). Aging: a theory based on free radical and radiation chemistry. J Gerontol, 11:298–300.
[31] Harman D (1972). The biologic clock: the mitochondria?. J. Am. Geriatr. Soc., 20: 145–147.
[32] Miquel J,Economos AC,Fleming J,Johnson Jr JE (1980). Mitochondrial role in cell aging. Exp Gerontol, 15:575–591.
[33] Pak JW,Herbst A,Bua E,Gokey N,McKenzie D,Aiken JM (2003). Mitochondrial DNA mutations as a fundamental mechanism in physiological declines associated with aging. Aging Cell, 2:1–7.
[34] Wei YH (1992). Mitochondrial DNA alterations as ageing-associated molecular events. Mutat Res, 275:145–155.
[35] Richter C (1995). Oxidative damage to mitochondrial DNA and its relationship to ageing. Int. J. Biochem. Cell Biol, 27:647–653.
[36] Linnane AW,Marzuki S,Ozawa T,Tanaka M (1989). Mitochondrial DNA mutations as an important contributor to ageing and degenerative diseases. Lancet, 1: 642–645.
[37] Judge S,Leeuwenburgh C (2007). Cardiac mitochondrial bioenergetics, oxidative stress, and aging. Am J Physiol Cell Physiol, 292:C1983–C1992.
[38] Sohal RS,Weindruch R (1996). Oxidative stress, caloric restriction, and aging. Science: 5: 59–63.
[39] Beckman KB,Ames BN (1998). The free radical theory of aging matures. Physiol Rev, 78: 547–581.
[40] Cortopassi GA,Shibata D,Soong NW,Arnheim NA (1992). A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA, 89:7370–7374.
[41] Hayakawa M,Hattori K,Sugiyama S,Ozawa T (1992). Age-associated oxygen damage and mutations in mitochondrial DNA in human hearts. Biochem Biophys Res Commun, 189(2):979–85.
[42] Paradies G,Ruggiero FM,Quagliariello E (1992).Age-dependent changes in the activity of anion carriers and in the lipid composition in rat heart mitochondria. Ann NY Acad Sci, 26:160–164.
[43] Paradies G,uggiero FM,Quagliariello E (1992). Age-dependent changes in the activity of anion carriers and in the lipid composition in rat heart mitochondria. Ann NY Acad Sci, 26:160–164.
[44] Shigenaga MK,Hagen TM, Ames BN (1994). Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci USA, 91:10771–10778.
[45] Lesnefsky EJ,Moghaddas S,Tandler B,Kerner J,Hoppel CL (2001). Mitochondrial dysfunction in cardiac disease: ischemia-reperfusion, aging, and heart failure. J Mol Cell Cardiol, 33:1065–1089.
[46] Paradies G,Petrosillo G,Paradies V,Ruggiero FM (2010). Oxidative stress, mitochondrial bioenergetics, and cardiolipin in aging. Free Radic Biol Med, 48(10):1286–95.
[47] Wellen KE,Hotamisligil GS (2005). Inflammation, stress, and diabetes. J Clin Invest, 115:1111–9.
[48] Stocker R,Keaney Jr JF (2004). Role of oxidative modifications in atherosclerosis. Physiol Rev, 84:1381–478.
[49] Furukawa S,Fujita T,Shimabukuro M,Iwaki M,Yamada Y,Nakajima Y (2004). Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest, 114:1752–61.
[50] Grattagliano I,Vendemiale G,Boscia F,Micelli-Ferrari T,Cardia L,Altomare E (1998). Oxidative retinal products and ocular damages in diabetic patients. Free Radic Biol Med, 25:369–72.
[51] Grattagliano I,Vendemiale G,Caraceni P,Domenicali M,Nardo B,Cavallari A (2000). Starvation impairs antioxidant defense in fatty livers of rats fed a choline-deficient diet. J Nutr, 130(9):2131–6.
[52] Portincasa P.,Grattagliano I.,Palmieri V.O.,Palasciano G (2005). Nonalcoholic steatohepatitis: recent advances from experimental models to clinical management. Clin Biochem, 38:203–217.
[53] Sies H (1997). Oxidative stress: oxidants and antioxidants. Exp Physiol, 82:291–295.
[54] Vendemiale G.,Grattagliano I.,Altomare E (1999). An update on the role of free radicals and antioxidant defense in human disease. Int J Clin Lab Res, 29: 49–55.
[55] Knopp RH,Paramsothy P (2006). Oxidized LDL and abdominal obesity: a key to understanding the metabolic syndrome. Am J Clin Nutr, 83(1):1–2.
[56] Sáez GT,Tormos C,Giner V,Chaves J,Lozano JV,Iradi A, (2004). Factors related to the impact of antihypertensive treatment in antioxidant activities and oxidative stress by-products in human hypertension. Am J Hypertens, 17:809–16.
[57] Palmieri VO,Grattagliano I,Portincasa P,Palasciano G (2006). Systemic oxidative alterations are associated with visceral adiposity and liver steatosis in patients with metabolic syndrome. J Nutr, 136:3022–6.
[58] Couillard C,Ruel G,Archer WR,Pomerleau S,Bergeron J,Couture P (2005). Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity. J Clin Endocrinol Metab, 90:6454–9.
[59] Keaney JFJr,Larson MG,Vasan RS,Wilson PW,Lipinska I,Corey D (2003). Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol, 23:434–9.
[60] Pinzani M,Marra F,Carloni V (1998). Signal transduction in hepatic stellate cells. Liver, 18:2–13.
[61] Suthanthiran M.,Anderson M.E.,Sharma V.K.,Meister A (1990). Glutathione regulates activation-dependent DNA synthesis in highly purified normal human T lymphocytes stimulated via the CD2 and CD3 antigens. Proc Natl Acad Sci U S A, 87:3343–3347.
[62] Sahaf B,Heydari K,Herzenberg LA,Herzenberg LA (2005). The extracellular microenvironment plays a key role in regulating the redox status of cell surface proteins in HIV-infected subjects. Arch Biochem Biophys, 434:26–32.
[63] Vendemiale G,Guerrieri F,Grattagliano I,Didonna D,Muolo L,Altomare E (1995). Mitochondrial oxidative phosphorylation and intracellular glutathione compartmentation during rat liver regeneration. Hepatology, 21:1450–1454.
[64] Grattagliano I,Palmieri VO,Portincasa P,Moschetta A,Palasciano G (2008). Oxidative stress-induced risk factors associated with the metabolic syndrome: a unifying hypothesis. J Nutr Biochem, 19(8):491–504.
[65] Czech MP,Lawrence JCJr,Lynn WS (1974). Evidence for the involvement of sulfhydryl oxidation in the regulation of fat cell hexose transport by insulin. Proc Natl Acad Sci SA, 71:4173–4177.
[66] Higaki Y,Mikami T,Fujii N,Hirshman MF,Koyama K,Seino T (2008). Oxidative stress stimulates skeletal muscle glucose uptake through a phosphatidylinositol-3-kinase dependent pathway. Am J Physiol Endocrinol Metab, 294:E889–E897.
[67] May JM,de Haen C (1979). The insulin-like effect of hydrogen peroxide on pathways of lipid synthesis in rat adipocytes. J Biol Chem, 254:9017–9021.
[68] Powell DJ,Hajduch E,Kular G,Hundal HS (2003). Ceramide disables 3-phosphoinositide binding to the pleckstrin homology domain of protein kinase B (PKB)/Akt by a PKCzeta-dependent mechanism. Mol Cell Biol, 23:7794–7808.
[69] Pessler D,Rudich A,Bashan N (2001). Oxidative stress impairs nuclear proteins binding to the insulin responsive element in the GLUT4 promoter. Diabetologia, 44:2156–2164.
[70] Kamigaki M,Sakaue S,Tsujino I,Ohira H,Ikeda D,Itoh N,Ishimaru S,Ohtsuka Y,Nishimura M (2006). Oxidative stress provokes atherogenic changes in adipokine gene expression in 3T3-L1 adipocytes. Biochem Biophys Res Commun, 339:624–632.
[71] Furukawa S,Fujita T,Shimabukuro M,Iwaki M,Yamada Y,Nakajima Y (2004) Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest, 114:1752–1761.
[72] Svegliati-Baroni G,Candelaresi C,Saccomanno S,Ferretti G,Bachetti T,Marzioni M (2006). A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury. Am J Pathol, 169:846–860.
[73] Schaffer SW,Jong CJ,Mozaffari M (2012). Role of oxidative stress in diabetes-mediated vasculardysfunction: Unifying hypothesis of diabetes revisited. Vascul Pharmacol, 57:139–149.
[74] Campia U,Tesauro M,Cardillo C (2012). Human obesity and endothelium-dependent responsiveness. Br J Pharmacol, 165:561–573.
[75] Tesauro M,Cardillo C (2011). Obesity, blood vessels and metabolic syndrome. Acta Physiol (Oxf), 203:279–286.
[76] Stadler K (2012). Oxidative stress in diabetes. Adv Exp Med Biol, 771: 272–287.
[77] Davi G,Ciabattoni G,Consoli A,Mezzetti A,Falco A,Santarone Set al (1999). In vivo formation of 8-iso-prostaglandin F2alpha and platelet activation in diabetes mellitus: effects of improved metabolic control and vitamin E supplementation. Circulation, 99:224–229.
[78] Davi G,Chiarelli F,Santilli F,Pomilio M,Vigneri S,Falco A (2003). Enhanced lipid peroxidation and platelet activation in the early phase of type 1 diabetes mellitus: role of interleukin-6 and disease duration. Circulation, 107:3199–3203.
[79] Monnier L,Mas E,Ginet C,Michel F,Villon L,Cristol JP (2006). Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA, 295(14):1681–7.
[80] Pitocco D,Zaccardi F,Di Stasio E,Romitelli F,Martini F,Scaglione GL (2009). Role of asymmetric-dimethyl-L-arginine (ADMA) and nitrite/nitrate (NOx) in the pathogenesis of oxidative stress in female subjects with uncomplicated type 1 diabetes mellitus. Diabetes Res Clin Pract, 86(3):173–6.
[81] Pitocco D,Zaccardi F,Di Stasio E,Romitelli F,Santini SA,Zuppi C (2010). Oxidative stress, nitric oxide, and diabetes. Rev Diabet Stud, 7(1):15–25.
[82] Wellen KE,Hotamisligil GS (2003). Obesity-induced inflammatory changes in adipose tissue. J Clin Invest, 112:1785–8.
[83] Lugogo NL,Bappanad D,Kraft M (2011). Obesity, metabolic dysregulation and oxidative stress in asthma. Biochim Biophys Acta, 1810:1120–6.
[84] Keaney JFJr.,Larson MG,Vasan RS,Wilson P W,LIpinska I,Corey D (2003). Obesity and systemic oxidative stress: clinical correlates of oxidative stress in the Framingham Study. Arterioscler Thromb Vasc Biol, 23: 434–439.
[85] Vincent HK,Bourguignon CM,Taylor AG (2010). Relationship of the dietary phytochemical index to weight gain, oxidative stress and inflammation in overweight young adults. J Hum Nutr Diet, 23:20–9.
[86] Couillard C,Ruel G,Archer WR,Pomerleau S,Bergeron J,Couture P (2005). Circulating levels of oxidative stress markers and endothelial adhesion molecules in men with abdominal obesity. J Clin Endocrinol Metab, 90:6454–9.
[87] Fujita K,Nishizawa H,Funahashi T,Shimomura I,Shimabukuro M (2006). Systemic oxidative stress is associated with visceral fat accumulation and the metabolic syndrome. Circ J, 70(11):1437–42.
[88] Steffes MW,Gross MD,Lee DH,Schreiner PJ,Jacobs DRJr (2006). Adiponectin, visceral fat, oxidative stress, and early macrovascular disease: the Coronary Artery Risk Development in Young Adults Study. Obesity, 14(2):319–26.
[89] Wu B,Fukuo K,Suzuki K,Yoshino G,Kazumi T (2009). Relationships of systemic oxidative stress to body fat distribution, adipokines and inflammatory markers in healthy middle-aged women. Endocr J, 56(6):773–82.
[90] Shaheen M,Echeverry D,Oblad MG,Montoya MI,Teklehaimanot S,Akhtar AJ (2007). Hepatitis C, metabolic syndrome, and inflammatory markers: results from the Third National Health and Nutrition Examination Survey [NHANES III]. Diabetes Res Clin Pract, 75(3):320–6.
[91] Roberts CK,Sindhu KK (2009). Oxidative stress and metabolic syndrome. Life Sci, 84(21–22):705–12.
[92] Nayak DU,Karmen C,Frishman WH,Vakili BA (2001). Antioxidant vitamins and enzymatic and synthetic oxygen-derived free radical scavengers in the prevention and treatment of cardiovascular disease. Heart Dis, 3:28–45.
[93] Kizhakekuttu TJ,Widlansky ME (2010). Natural antioxidants and hypertension: promise and challenges. Cardiovasc Ther, 28:e20–e32.
[94] Kitiyakara C,Wilcox C (1998). Antioxidants for hypertension. Curr Opin Nephrol Hypertens, 7:531–538.
[95] Russo C,Olivieri O,Girelli D,Faccini G,Zenari ML,Lombardi S,Corrocher R (1998). Antioxidant status and lipid peroxidation in patients with essential hypertension. J Hypertens, 16:1267–1271.
[96] Tse WY,Maxwell SR,Thomason H,Blann A,Thorpe GH,Waite M (1994). Antioxidant status in controlled and uncontrolled hypertension and its relationship to endothelial damage. J Hum Hypertens.;8:843–849.
[97] Mansego ML,Solar Gde M,Alonso MP,Martínez F,Sáez GT,Escudero JC (2011) Polymorphisms of antioxidant enzymes, blood pressure and risk of hypertension. J Hypertens, 29:492–500.
[98] Galley HF,Thornton J,Howdle PD,Walker BE,Webster NR (1997). Combination oral antioxidant supplementation reduces blood pressure. Clin Sci, 92:361–365.
[99] Broadhurst CL (1997). Balanced intakes of natural triglycerides for optimum nutrition: an evolutionary and phytochemical perspective. Med Hypotheses, 49:247–261.
[100] Houston MC (2007). Treatment of hypertension with nutraceuticals. vitamins, antioxidants and minerals. Expert Rev Cardiovasc Ther, 5:681–691.
[101] Dhalla NS,Temsah RM,Netticadam T (2000). The role of oxidative stress in cardiovascular diseases. J Hypertens, 18:655–673.
[102] Touyz RM (2004). Reactive oxygen species, vascular oxidative stress, and redox signaling in hypertension: what is the clinical significance?. Hypertension, 44(3):248–52.
[103] Nishihara M,Hirooka Y,Matsukawa R,Kishi T,Sunagawa K (2012). Oxidative stress in the rostral ventrolateral medulla modulates excitatory and inhibitory inputs in spontaneously hypertensive rats. J. Hypertension, 30: 97–106.
[104] Konno S,Hirooka Y,Kishi T,Sunagawa K (2012). Sympathoinhibitory effects of telmisartan through the reduction of oxidative stress in the rostral ventrolateral medulla of obesity-induced hypertensive rats. J Hypertens, 30:1992–1999.
[105] Houston M (2013). Nutrition and nutraceutical supplements for the treatment of hypertension: part I. J Clin Hypertens, 15(10):752–7.
[106] Brownlee M (2001). Biochemistry and molecular cell biology of diabetic complications. Nature, 414: 813–820.
[107] Avignon A,Radauceanu A,Monnier L (1997). Nonfasting plasma glucose is a better marker of diabetic control than fasting plasma glucose in type 2 diabetes. Diabetes Care, 20:1822–1826.
[108] El-Kebbi IM,Ziemer DC,Cook CB,Gallina DL,Barnes CS,Philipps LS (2004). Utility of casual postprandial glucose levels in type 2 diabetes management. Diabetes Care, 27:335–339.
[109] Rohlfing CL,Wiedmeyer HS,Little RR,England JD,Tennill A,Goldstein DE (2002). Defining the relationship between plasma glucose and HbA1c. Diabetes Care, 25:275–278.
[110] American Diabetes Association (2007). Standards of medical care in diabetes-2007. Diabetes Care, 30(S1):S4–S41.
[111] Sacks DB,Bruns DE,Goldstein DE,Mac Laren NK,Mac Donald JM,Parrott M (2002). Guidelines and recommendations for laboratory analysis in the diagnosis and management of diabetes mellitus (position statement). Diabetes Care, 25:750–786.
[112] Gorus F,Mathieu C,Gerlo E (2006). How should HbA1 measurements be reported?. Diabetologia, 49:7–10.
[113] Morrow JD,Hill KE,Burk RF,Nammour TM,Badr KF,Roberts LJ (1991). A series of prostaglandin F2-like compounds are produced in vivo in humans by non-cyclooxygenase free radical-catalyzed mechanism. Proc Natl Acad Sci USA, 87:9383–9387.
[114] Roberts LJ,Morrow JD (2000). Measurement of F (2)-isoprostanes as an index of oxidative stress in vivo. Free Radic Bio Med, 28:505–513.
[115] Basu S (1998). Metabolism of 8-iso-prostaglandin F2α. FEBS Lett, 428:32–36.
[116] Davi G,Falco A,Patrono C (2005). Lipid peroxidation in diabetes mellitus. Antioxid Redox Signal, 7:256–258.
[117] Monnier L,Mas E,Ginet C,Michel F,Villon L,Cristol J-P (2006). Activation of oxidative stress by acute glucose fluctuations compared with sustained chronic hyperglycemia in patients with type 2 diabetes. JAMA, 295:1681–1687.
[118] Colette C,Monnier L (2007). Acute glucose fluctuations and chronic sustained hyperglycemia as risk factors for cardiovascular diseases in patients with type 2 diabetes. Horm Metab Res, 39(9):683–6.
[119] Ruotolo G,Howard BV (2002). Dyslipidemia of the metabolic syndrome. Curr Cardiol Rep, 4:494–500.
[120] Jeppesen J,Hollenbeck CB,Zhou MY,Coulston AM,Jones C,Chen YDet al (1995). Relation between insulin resistance, hyperinsulinemia, postheparin plasma lipoprotein lipase activity, and postprandial lipemia. Arterioscler Thromb Vasc Biol, 15:320–4.
[121] de Oliveira J,Hort MA,Moreira EL,Glaser V,Ribeiro-do-Valle RM,Prediger RD (2011). Positive correlation between elevated plasma cholesterol levels and cognitive impairments in LDL receptor knockout mice: relevance of cortico-cerebral mitochondrial dysfunction and oxidative stress. Neuroscience, 197:99–106.
[122] Marques de Mattos A,Marino LV,Ovidio PP,Jordão AA,Almeida CC,Chiarello PG (2012). Protein oxidative stress and dyslipidemia in dialysis patients. Ther Apher Dial, 16:68–74.
[123] Zelzer S,Fuchs N,Almer G,Raggam RB,Prüller F,Truschnig-Wilders M (2011). High density lipoprotein cholesterol level is a robust predictor of lipid peroxidation irrespective of gender, age, obesity, and inflammatory or metabolic biomarkers. Clin Chim Acta, 412:1345–9.
[124] Andreadou I,Farmakis D,Prokovas E,Sigala F,Zoga A,Spyridaki K (2012). Short-term statin administration in hypercholesterolaemic rabbits resistant to postconditioning: effects on infarct size, endothelial nitric oxide synthase, and nitro-oxidative stress. Cardiovasc Res, 94:501–9.
[125] Ansari JA,Bhandari U,Pillai KK,Haque SE (2012). Effect of rosuvastatin on obesity-induced cardiac oxidative stress in Wistar rats--a preliminary study. Indian J Exp Biol, 50(3):216–22.
[126] Hutcheson R,Rocic P (2012). The metabolic syndrome, oxidative stress,environment, and cardiovascular disease: the great exploration. Exp Diabetes Res, 2012: 271028.
[127] Guarner V,Carbó R,Rubio ME, Baños de MacCarthy G (2005). Aging of the cardiovascular system. In:Benhagen EF, editor. Hypertension: New research. Nova Biomedical Books; USA, 47–68.
[128] Kenyon CJ (2010). The genetics of aging. Nature, 464:504–512.
[129] Rincon M,Rudin E,Barzilai N (2005). The insulin/IGF-1 signaling in mammals and its relevance to human longevity. Exp Gerontol, 40:873–877.
[130] Rozing MP,Westendorp RGJ,Frölich M,de Craen AJM,Beekman M,Heijmans BT (2009). Human insulin/IGF-1 and familial longevity at middle age. Aging, 1:714–722.
[131] Guarner V,Carbó R,Rubio ME,Baños de MacCarthy G (2005). Aging of the cardiovascular system. In:Benhagen EF, editor. Hypertension: New Research. USA: Nova Biomedical Books Publishers, 47–68.
[132] Baños G,El Hafidi M,Pérez-Torres I,Guarner V (2009). Insulin resistance and the metabolic syndrome. In:Yao EB, editor. Insulin Resistance: New Research. USA: Nova Biomedical Books Publishers, 49–97.
[133] Guarner V,Rubio-Ruiz ME,Perez-Torres I,Baños de McCarthy G (2011). Relation of aging and sex hormones to metabolic syndrome and cardiovascular disease. Exp Gerontol, 46:517–523.
[134] Fadini GP,Ceolotto G,Pagnin E,de Kreutzenberg S,Avogaro A (2011). At the crossroads of longevity and metabolism: the metabolic syndrome and lifespan determinant pathways. Aging Cell, 10:10–17.
[135] Ren J,Pulakat L,Whaley-Connell A,Sowers JR (2010). Mitochondrial biogenesis in the metabolic syndrome and cardiovascular disease. Mol Med, 88:993–1001.
[136] Veronica G,Esther RR (2012). Aging, metabolic syndrome and the heart. Aging Dis, 3:269–79.
[137] Passos JF,Saretzki G,Ahmed S,Nelson G,Richter T,Peters H (2007). Mitochondrial dysfunction accounts for the stochastic heterogeneity in telomere-dependent senescence. PLoS Biol, 5:e110.
[138] Bonomini F,Rodella LF,Moghadasian M,Lonati C,Coleman R,Rezzani R (2011). Role of apolipoprotein E in renal damage protection. Histochem Cell Biol, 135(6):571–9.
[139] Kong CM,Lee XW,Wang X (2013). Telomere shortening in human diseases. FEBS J, 280:3180–93.
[1] Chiara Priami,Giulia De Michele,Franco Cotelli,Alessandro Cellerino,Marco Giorgio,Pier Giuseppe Pelicci,Enrica Migliaccio. Modelling the p53/p66Shc Aging Pathway in the Shortest Living Vertebrate Nothobranchius Furzeri[J]. A&D, 2015, 6(2): 95-108.
[2] Stambler Ilia. Stop Aging Disease! ICAD 2014[J]. A&D, 2015, 6(2): 76-94.
[3] Alexandra Moura,José Madureira,Pablo Alija,João Carlos Fernandes,José Gerardo Oliveira,Martin Lopez,Madalena Filgueiras,Leonilde Amado,Maria Sameiro-Faria,Vasco Miranda,Alice Santos-Silva,Elísio Costa. Effect of Aging in the Perception of Health-Related Quality of Life in End-Stage Renal Disease Patients under Online-Hemodiafiltration[J]. Aging and Disease, 2015, 6(1): 17-26.
[4] Amanda Piano,Vladimir I. Titorenko. The Intricate Interplay between Mechanisms Underlying Aging and Cancer[J]. Aging and Disease, 2015, 6(1): 56-75.
[5] Kunlin Jin,James W. Simpkins,Xunming Ji,Miriam Leis,Ilia Stambler. The Critical Need to Promote Research of Aging and Aging-related Diseases to Improve Health and Longevity of the Elderly Population[J]. Aging and Disease, 2015, 6(1): 1-5.
[6] Shinichi Iwasaki,Tatsuya Yamasoba. Dizziness and Imbalance in the Elderly: Age-related Decline in the Vestibular System[J]. Aging and Disease, 2015, 6(1): 38-47.
[7] Baugé Catherine,Girard Nicolas,Lhuissier Eva,Bazille Celine,Boumediene Karim. Regulation and Role of TGFβ Signaling Pathway in Aging and Osteoarthritis Joints[J]. Aging and Disease, 2014, 5(6): 394-405.
[8] Juliane Schulze,Antje Vogelgesang,Alexander Dressel. Catecholamines, Steroids and Immune Alterations in Ischemic Stroke and Other Acute Diseases[J]. Aging and Disease, 2014, 5(5): 327-339.
[9] David Blokh,Ilia Stambler. Estimation of Heterogeneity in Diagnostic Parameters of Age-related Diseases[J]. Aging and Disease, 2014, 5(4): 218-225.
[10] Olaoluwa O Okusaga. Accelerated Aging in Schizophrenia Patients: The Potential Role of Oxidative Stress[J]. Aging and Disease, 2014, 5(4): 256-262.
[11] Shaohua Xu,Ying Cai,Yuehua Wei. mTOR Signaling from Cellular Senescence to Organismal Aging[J]. Aging and Disease, 2014, 5(4): 263-273.
[12] Alejandro Lucas-Sánchez,Pedro Francisco Almaida-Pagán,Pilar Mendiola,Jorge de Costa. Nothobranchius as a model for aging studies. A review[J]. Aging and Disease, 2014, 5(4): 281-291.
[13] Chandan Prasad,Victorine Imrhan,Francesco Marotta,Shanil Juma,Parakat Vijayagopal. Lifestyle and Advanced Glycation End Products (AGEs) Burden: Its Relevance to Healthy Aging[J]. Aging and Disease, 2014, 5(3): 212-217.
[14] Ninu Poulose,Raghavan Raju. Aging and Injury: Alterations in Cellular Energetics and Organ Function[J]. Aging and Disease, 2014, 5(2): 101-108.
[15] Peter M Nilsson. Hemodynamic Aging as the Consequence of Structural Changes Associated with Early Vascular Aging (EVA)[J]. Aging and Disease, 2014, 5(2): 109-113.
Full text



Copyright © 2014 Aging and Disease, All Rights Reserved.
Address: Aging and Disease Editorial Office 3400 Camp Bowie Boulevard Fort Worth, TX76106 USA
Fax: (817) 735-0408 E-mail:
Powered by Beijing Magtech Co. Ltd