Melatonin and the theories of aging: A critical appraisal of melatonin's role in antiaging mechanisms

Journal of Pineal Research

Volumn 55, Issue 4, 2013, Pages 325-356

  Hardeland, Rüdigger ^a  

^a UNIVERSITY OF GÖTTINGEN   (Germany)

Author keywords

free radicals; inflammaging; metabolic sensing; mitochondria; SAMP8; senescence associated secretory phenotype; stem cells

Indexed keywords

CYTOKINE; FREE RADICAL; GLIAL CELL LINE DERIVED NEUROTROPHIC FACTOR; GLUCOSE; GROWTH HORMONE; HEME OXYGENASE 1; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; INDUCIBLE NITRIC OXIDE SYNTHASE; INSULIN; KAINIC ACID; MELATONIN; MEMANTINE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN KINASE B; SIRTUIN; SOMATOMEDIN C; THAPSIGARGIN; TISSUE PLASMINOGEN ACTIVATOR; TRANSCRIPTION FACTOR CLOCK; VASCULOTROPIN; WORTMANNIN;

ADIPOCYTE; AGING; ANTI AGING ACITIVITY; APOPTOSIS; ASTROCYTE; BLOOD VESSEL; BRAIN; CANCER CELL; CANCER STEM CELL; CELL STRAIN HEPG2; CIRCADIAN RHYTHM; DOWN REGULATION; DRUG ACTIVITY; DRUG ANTAGONISM; ENDOPLASMIC RETICULUM STRESS; ENZYME ACTIVATION; EPITHELIUM CELL; GLUCOSE BLOOD LEVEL; GROWTH HORMONE RELEASE; HEART; HEMORRHAGIC SHOCK; HIPPOCAMPUS; HUMAN; HUMAN CELL CULTURE; HYPOTHALAMUS; INSULIN SENSITIVITY; LIFESPAN; LIPID DIET; LIVER; LIVER ISCHEMIA; METABOLIC SYNDROME X; MITOCHONDRION; MITOSIS INHIBITION; MUELLER CELL; NONHUMAN; OCCLUSIVE CEREBROVASCULAR DISEASE; OSTEOBLAST; OXIDATIVE STRESS; PHENOTYPE; PLEIOTROPY; PRIMARY CULTURE; PROTEIN PHOSPHORYLATION; PYRAMIDAL NERVE CELL; QUALITY OF LIFE; REPERFUSION INJURY; REVIEW; SENESCENCE; SHEAR STRESS; TELOMERE; TISSUE REGENERATION; UPREGULATION;

FREE RADICALS; INFLAMMAGING; METABOLIC SENSING; MITOCHONDRIA; SAMP8; SENESCENCE-ASSOCIATED SECRETORY PHENOTYPE; STEM CELLS;

AGING; ANIMALS; CELL AGING; FREE RADICALS; HUMANS; MELATONIN; METABOLIC SYNDROME X; MODELS, BIOLOGICAL; STEM CELLS;

EID: 84885640190     PISSN: 07423098     EISSN: 1600079X     Source Type: Journal    
DOI: 10.1111/jpi.12090     Document Type: Review

References (453)

1. Hardeland R, Coto-Montes A,. New vistas on oxidative damage and aging. Open Biol J 2010; 3: 39-52.
2. Harman D,. Aging: a theory based on free radical and radiation chemistry. J Gerontol 1956; 11: 298-300.
3. Harman D,. Free radical theory of aging: an update: increasing the functional life span. Ann N Y Acad Sci 2006; 1067: 10-21.
4. Afanas'ev I,. Signaling and damaging functions of free radicals in aging-free radical theory, hormesis, and TOR. Aging Dis 2010; 1: 75-88.
5. Harman D,. The biologic clock: the mitochondria? J Am Geriatr Soc 1972; 20: 145-147.
6. Miquel J, Economos AC, Fleming J, et al. Mitochondrial role in cell aging. Exp Gerontol 1980; 15: 575-591.
7. Miquel J, de Juan E, Sevila I,. Oxygen-induced mitochondrial damage and aging. EXS 1992; 62: 47-57.
8. Gemma C, Vila J, Bachstetter A, et al. Oxidative stress and the aging brain: from theory to prevention. In: Brain Aging: Models, Methods, and Mechanisms, Riddle DR, ed., CRC Press, Boca Raton, FL, 2007; chapter 15 [PMID: 21204345].
9. Gruber J, Schaffer S, Halliwell B,. The mitochondrial free radical theory of aging-where do we stand? Front Biosci 2008; 13: 6554-6579.
10. Gomez-Cabrera MC, Sanchis-Gomar F, Garcia-Valles R, et al. Mitochondria as sources and targets of damage in cellular aging. Clin Chem Lab Med 2012; 50: 1287-1295.
11. Franceschi C, Bonafè M, Valensin S, et al. Inflamm-aging. An evolutionary perspective in immunosenescence. Ann N Y Acad Sci 2000; 908: 244-254.
12. Boren E, Gershwin ME,. Inflamm-aging: autoimmunity, and the immune-risk phenotype. Autoimmun Rev 2004; 3: 401-406.
13. Capri M, Monti D, Salvioli S, et al. Complexity of anti-immunosenescence strategies in humans. Artif Organs 2006; 30: 730-742.
14. Salvioli S, Capri M, Valensin S, et al. Inflamm-aging, cytokines and aging: state of the art, new hypotheses on the role of mitochondria and new perspectives from systems biology. Curr Pharm Des 2006; 12: 3161-3171.
15. Salminen A, Ojala J, Huuskonen J, et al. Interaction of aging-associated signaling cascades: inhibition of NF-κB signaling by longevity factors FoxOs and SIRT1. Cell Mol Life Sci 2008; 65: 1049-1058.
16. De la Fuente M, Miquel J,. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des 2009; 15: 3003-3026.
17. Cevenini E, Monti D, Franceschi C,. Inflamm-aging. Curr Opin Clin Nutr Metab Care 2013; 16: 14-20.
18. Hwang JW, Yao H, Caito S, et al. Redox regulation of SIRT1 in inflammation and cellular senescence. Free Radic Biol Med 2013; 61C: 95-110.
19. Pearl R,. The Rate of Living: Being an Account of Some Experimental Studies on the Biology of Life Duration. AA Knopf, New York, NY, 1928.
20. Speakman JR, Selman C, McLaren JS, et al. Living fast, dying when? The link between aging and energetics. J Nutr 2002; 132: 1583S-1597S.
21. Speakman JR,. Body size, energy metabolism and lifespan. J Exp Biol 2005; 208: 1717-1730.
22. Candore G, Colonna-Romano G, Balistreri CR, et al. Biology of longevity; role of the innate immune system. Rejuvenation Res 2006; 9: 143-148.
23. Morin GB,. Telomere control of replicative lifespan. Exp Gerontol 1997; 32: 375-382.
24. Goyns MH, Lavery WL,. Telomerase and mammalian ageing: a critical appraisal. Mech Ageing Dev 2000; 114: 69-77.
25. Zucchero T, Ahmed S,. Genetics of proliferative aging. Exp Gerontol 2006; 41: 992-1000.
26. Eisenberg DT,. An evolutionary review of human telomere biology: the thrifty telomere hypothesis and notes on potential adaptive paternal effects. Am J Hum Biol 2011; 23: 149-167.
27. Conboy IN, Rando TA,. Aging, stem cells and tissue regeneration: lessons from muscle. Cell Cycle 2005; 4: 407-410.
28. Pekovic V, Hutchinson CJ,. Adult stem cell maintenance and tissue regeneration in the ageing context: the role for A-type lamins as intrinsic modulators of ageing in adult stem cells and their niches. J Anat 2008; 213: 5-25.
29. Cerletti M, Shadrach JL, Jurga S, et al. Regulation and function of skeletal muscle stem cells. Cold Spring Harb Symp Quant Biol 2008; 73: 317-322.
30. Mimeault M, Batra SK,. Aging of tissue-resident adult stem/progenitor cells and their pathological consequences. Panminerva Med 2009; 51: 57-79.
31. Wang J, Geiger H, Rudolph KL,. Immunoaging induced by hematopoietic stem cell aging. Curr Opin Immunol 2011; 23: 532-536.
32. Galetta F, Carpi A, Abraham N, et al. Age related cardiovascular dysfunction and effects of physical activity. Front Biosci (Elite Ed) 2012; 4: 2617-2637.
33. Smith BC, Hallows WC, Denu JM,. Mechanisms and molecular probes of sirtuins. Chem Biol 2008; 15: 1002-1013.
34. Guarente L,. Mitochondria-a nexus for aging, calorie restriction, and sirtuins? Cell 2008; 132: 171-176.
35. Bostock CV, Soiza RL, Whalley LJ,. Genetic determinants of ageing processes and diseases in later life. Maturitas 2009; 62: 225-229.
36. Ljubuncic P, Reznick AZ,. The evolutionary theories of aging revisited-a mini-review. Gerontology 2009; 55: 205-216.
37. Shoba B, Lwin ZM, Ling LS, et al. Function of sirtuins in biological tissues. Anat Rec (Hoboken) 2009; 292: 536-543.
38. Alcaín FJ, Villalba JM,. Sirtuin activators. Expert Opin Ther Pat 2009; 19: 403-414.
39. Hall JA, Dominy JE, Lee Y, et al. The sirtuin family's role in aging and age-associated pathologies. J Clin Invest 2013; 123: 873-979.
40. Morris BJ,. Seven sirtuins for seven deadly diseases of aging. Free Radic Biol Med 2013; 56: 133-171.
41. Radak Z, Kiltai E, Taylor AW, et al. Redox-regulating sirtuins in aging, caloric restriction, and exercise. Free Radic Biol Med 2013; 58: 87-97.
42. Kloet DE, Burgering BM,. The PKB/FOXO switch in aging and cancer. Biochim Biophys Acta 2011; 1813: 1926-1937.
43. Monsalve M, Olmos Y,. The complex biology of FOXO. Curr Drug Targets 2011; 12: 1322-1350.
44. Perez FP, Moinuddin SS, ul ain Shamim Q, et al. Longevity pathways: HSF1 and FoxO pathways, a new therapeutic target to prevent age-related diseases. Curr Aging Sci 2012; 5: 87-95.
45. Kurosu H, Yamamoto M, Clark JD, et al. Suppression of aging in mice by the hormone Klotho. Science 2005; 309: 1829-1833.
46. Sato I, Miyado M, Sunohara M,. NADH dehydrogenase activity and expression of mRNA of complex I (ND1, 51kDa, and 75kDa) in heart mitochondria of klotho mouse. Okajimas Folia Anat Jpn 2005; 82: 49-56.
47. Yamamoto M, Clark JD, Pastor JV, et al. Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 2005; 280: 38029-38034.
48. Haruna Y, Kashihara N, Satoh M, et al. Amelioration of progressive renal injury by genetic manipulation of Klotho gene. Proc Natl Acad Sci USA 2007; 104: 2331-2336.
49. Sinha J, Chen F, Miloh T, et al. β-Klotho and FGF-15/19 inhibit the apical sodium-dependent bile acid transporter in enterocytes and cholangiocytes. Am J Physiol Gastrointest Liver Physiol 2008; 295: G996-G1003.
50. Kurosu H, Kuro-o M,. The Klotho gene family and the endocrine fibroblast growth factors. Mol Cell Endocrinol 2009; 299: 72-78.
51. Wang Y, Sun Z,. Current understanding of klotho. Ageing Res Rev 2009; 8: 43-51.
52. Kuro-o M,. Klotho and the aging process. Korean J Intern Med 2011; 26: 113-122.
53. John GB, Cheng CY, Kuro-o M,. Role of Klotho in aging, phosphate metabolism, and CKD. Am J Kidney Dis 2011; 58: 127-134.
54. Chen CD, Sloane JA, Li H, et al. The antiaging protein Klotho enhances oligodendrocyte maturation and myelination of the CNS. J Neurosci 2013; 33: 1827-1939.
55. Armstrong SM, Redman JR,. Melatonin: a chronobiotic with anti-aging properties? Med Hypotheses 1991; 34: 300-309.
56. Rúzsás C, Mess B,. Melatonin and aging. A brief survey. Neuro Endocrinol Lett 2000; 21: 17-23.
57. Spindler SR, Mote PL,. Screening candidate longevity therapeutics using gene-expression arrays. Gerontology 2007; 53: 306-321.
58. Rodríguez MI, Escames G, Lõpez LC, et al. Improved mitochondrial function and increased life span after chronic melatonin treatment in senescent prone mice. Exp Gerontol 2008; 43: 749-756.
59. Magnanou E, Attia J, Fons R, et al. The timing of the shrew: continuous melatonin treatment maintains youthful rhythmic activity in aging Crocidura russula. PLoS ONE 2009; 4: e5904.
60. Poeggeler B, Reiter RJ, Tan D-X, et al. Melatonin, hydroxyl radical-mediated oxidative damage, and aging: a hypothesis. J Pineal Res 1993; 14: 151-168.
61. Ferrari CK,. Functional foods, herbs and nutraceuticals: towards biochemical mechanisms of healthy aging. Biogerontology 2004; 5: 275-289.
62. Harrod CG, Bendok BR, Batjer HH,. Interactions between melatonin and estrogen may regulate cerebrovascular function in women: clinical implications for the effective use of HRT during menopause and aging. Med Hypotheses 2005; 64: 725-735.
63. Ferrari E, Cravello L, Falvo F, et al. Neuroendocrine features in extreme longevity. Exp Gerontol 2008; 43: 88-94.
64. Korkmaz A, Reiter RJ, Topal T, et al. Melatonin: an established antioxidant worthy of use in clinical trials. Mol Med 2009; 15: 43-50.
65. Sánchez-Barcelõ EJ, Mediavilla MD, Tan D-X, et al. Clinical uses of melatonin: evaluation of human trials. Curr Med Chem 2010; 17: 2070-2095.
66. Rodella LF, Favero G, Rossini C, et al. Aging and vascular dysfunction: beneficial melatonin effects. Age (Dordr) 2013; 35: 103-115.
67. Reiter RJ, Tan D-X, Fuentes-Broto L,. Melatonin: a multitasking molecule. Prog Brain Res 2010; 181: 127-151.
68. Hardeland R, Cardinali DP, Srinivasan V, et al. Melatonin-a pleiotropic, orchestrating regulator molecule. Prog Neurobiol 2011; 93: 350-384.
69. Kowald A, Kirkwood TB,. A network theory of ageing: the interactions of defective mitochondria, aberrant proteins, free radicals and scavengers in the ageing process. Mutat Res 1996; 316: 209-236.
70. Ying W,. A new hypothesis of neurodegenerative diseases: the deleterious network hypothesis. Med Hypotheses 1996; 47: 307-313.
71. Ying W,. Deleterious network hypothesis of aging. Med Hypotheses 1997; 48: 143-148.
72. Kirkwood TB, Kowald A,. Network theory of aging. Exp Gerontol 1997; 32: 395-399.
73. Coppé JP, Patil CK, Rodier F, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogeneic RAS and p53 tumor suppressor. PLoS Biol 2008; 6: 2853-2868.
74. Fumagalli M, d'Adda di Fagagna F,. SASPense and DDRama in cancer and ageing. Nat Cell Biol 2009; 11: 921-923.
75. Young ARJ, Narita M,. SASP reflects senescence. EMBO Rep 2009; 10: 228-230.
76. Coppé JP, Desprez PY, Krtolica A, et al. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 2010; 5: 99-118.
77. Olivieri F, Rippo MR, Prattichizzo F, et al. Toll like receptor signaling in "inflammaging": microRNA as new players. Immun Ageing 2013; 10: 11.
78. Olivieri F, Rippo MR, Monsurrò V, et al. MicroRNAs linking inflamm-aging, cellular senescence and cancer. Ageing Res Rev 2013 [Epub ahead of print, May 17; pii:S1568-S1637(13)00023-8. doi: 10.1016/j.arr.2013.05.001 ].
79. Olivieri F, Lazzarini R, Babini L, et al. Anti-inflammatory effect of ubiquitinol-10 on young and senescent endothelial cells via miRNA-146a modulation. Free Radic Biol Med 2013; 63: 410-420.
80. Hardeland R,. Neuroprotection by radical avoidance: search for suitable agents. Molecules 2009; 14: 5054-5102.
81. Sansoni P, Vescovini R, Fagnoni F, et al. The immune system in extreme longevity. Exp Gerontol 2008; 43: 61-65.
82. Candore G, Caruso C, Colonna-Romano G,. Inflammation, genetic background and longevity. Biogerontology 2010; 11: 565-573.
83. Alonso-Fernández P, De la Fuente M,. Role of the immune system in aging and longevity. Curr Aging Sci 2011; 4: 78-100.
84. Salvioli S, Monti D, Lanzarini C, et al. Immune system, cell senescence, aging and longevity-inflamm-aging reappraised. Curr Pharm Des 2013; 19: 1675-1679.
85. Ungvari Z, Krasnikov BF, Csiszar A, et al. Testing hypotheses of aging in long-lived mice of the genus Peromyscus: association between longevity and mitochondrial stress resistance, ROS detoxification pathways, and DNA repair efficiency. Age (Dordr) 2008; 30: 121-133.
86. Ungvari Z, Buffenstein R, Austad SN, et al. Oxidative stress in vascular senescence: lessons from successfully aging species. Front Biosci 2008; 13: 5056-5070.
87. Shimokawa I, Chiba T, Yamaza H, et al. Longevity genes: insights from calorie restriction and genetic longevity models. Mol Cells 2008; 26: 427-435.
88. Guarente L,. Sirtuins in aging and disease. Cold Spring Harb Symp Quant Biol 2007; 72: 483-488.
89. Chen D, Bruno J, Easlon E, et al. Tissue-specific regulation of SIRT1 by calorie restriction. Genes Dev 2008; 22: 1753-1757.
90. Finley LW, Haigis MC,. The coordination of nuclear and mitochondrial communication during aging and calorie restriction. Ageing Res Rev 2009; 8: 173-188.
91. Jørgensen JO, Rubeck KZ, Nielsen TS, et al. Effects of GH in human muscle and fat. Pediatr Nephrol 2010; 25: 705-709.
92. Berryman DE, Glad CA, List EO, et al. The GH/IGF-1 axis in obesity: pathophysiology and therapeutic considerations. Nat Rev Endocrinol 2013; 9: 346-356.
93. Salminen A, Kaamiranta K,. Insulin/IGF-1 paradox of aging: regulation via AKT/IKK/NF-κB signaling. Cell Signal 2010; 22: 573-577.
94. Lombard DB, Alt FW, Cheng HL, et al. Mammalian Sir2 homolog SIRT3 regulates global mitochondrial lysine acetylation. Mol Cell Biol 2007; 27: 8807-8814.
95. Jacobs KM, Pennington JD, Bisht KS, et al. SIRT3 interacts with the daf-16 homolog FOXO3a in the mitochondria, as well as increases FOXO3a dependent gene expression. Int J Biol Sci 2008; 4: 291-299.
96. Ahn BH, Kim HS, Song S, et al. A role for the mitochondrial deacetylase Sirt3 in regulating energy homeostasis. Proc Natl Acad Sci USA 2008; 105: 14447-14452.
97. Dilova I, Easlon E, Lin SJ,. Calorie restriction and the nutrient sensing signaling pathways. Cell Mol Life Sci 2007; 64: 752-767.
98. Fulco M, Sartorelli V,. Comparing and contrasting the roles of AMPK and SIRT1 in metabolic tissues. Cell Cycle 2008; 7: 3669-3679.
99. Lõpez-Lluch G, Irusta PM, Navas P, et al. Mitochondrial biogenesis and healthy aging. Exp Gerontol 2008; 43: 813-819.
100. Csiszar A, Labinskyy N, Pinto JT, et al. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am J Physiol Heart Circ Physiol 2009; 297: H13-H20.
101. McCarty MF, Barroso-Aranda J, Contreras F,. The "rejuvenatory" impact of lipoic acid on mitochondrial function in aging rats may reflect induction and activation of PPAR-γ coactivator-1α. Med Hypotheses 2009; 72: 29-33.
102. Festuccia WT, Oztezcan S, Laplante M, et al. Peroxisome proliferator-activated receptor-γ-mediated positive energy balance in the rat is associated with reduced sympathetic drive to adipose tissues and thyroid status. Endocrinology 2008; 149: 2121-2130.
103. Ramirez SH, Heilman D, Morsey B, et al. Activation of peroxisome proliferator-activated receptor γ (PPARγ) suppresses Rho GTPases in human brain microvascular endothelial cells and inhibits adhesion and transendothelial migration of HIV-1 infected monocytes. J Immunol 2008; 180: 1854-1865.
104. Hyong A, Jadhav V, Lee S, et al. Rosiglitazone, a PPARγ agonist, attenuates inflammation after surgical brain injury in rodents. Brain Res 2008; 1215: 218-224.
105. Tsukuda K, Mogi M, Iwanami J, et al. Cognitive deficit in amyloid-β-injected mice was improved by pretreatment with a low dose of telmisartan partly because of peroxisome proliferator-activated receptor-γ activation. Hypertension 2009; 54: 782-787.
106. Wang CH, Lee WJ, Ghanta VK, et al. Molecules involved in the self-protection of neurons against glucose-oxygen-serum deprivation (GOSD)-induced cell damage. Brain Res Bull 2009; 79: 169-176.
107. Meng B, Zhang Q, Huang C, et al. Effects of a single dose of methylprednisolone versus three doses of rosiglitazone on nerve growth factor levels after spinal cord injury. J Int Med Res 2011; 39: 805-814.
108. Kishi T, Hirooka Y, Sunagawa J,. Telmisartan protects against cognitive decline via up-regulation of brain-derived neurotrophic factor/tropomyosin- related kinase B in hippocampus of hypertensive rats. J Cardiol 2012; 60: 489-494.
109. Wang SH, Guo YJ, Yuan Y, et al. PPARγ-mediated advanced glycation end products regulate neural stem cell proliferation but not neural differentiation through the BDNF-CREB pathway. Toxicol Lett 2011; 206: 339-346.
110. Izquierdo-Claros RM, Boyano-Adánez MC, Torrecillas G, et al. Acute modulation of somatostatin receptor function by melatonin in the rat frontoparietal cortex. J Pineal Res 2001; 31: 46-56.
111. Valcavi R, Dieguez C, Azzarito C, et al. Effect of oral administration of melatonin on GH response to GRF 1-44 in normal subjects. Clin Endocrinol (Oxf) 1987; 26: 453-458.
112. Nassar E, Mulligan C, Taylor L, et al. Effects of a single dose in N-Acetyl-5-methoxytryptamine (Melatonin) and resistance exercise on the growth hormone/IGF-1 axis in young males and females. J Int Soc Sports Nutr 2007; 4: 14.
113. Leproult R, Van Onderbergen A, L'Hermite-Balériaux M, et al. Phase-shifts of 24-h rhythms of hormonal release and body temperature following early evening administration of the melatonin agonist agomelatine in healthy older men. Clin Endocrinol 2005; 63: 298-304.
114. Mazzoccoli G, Sothern RB, Pazienza V, et al. Circadian aspects of growth hormone-insulin-like growth factor axis function in patients with lung cancer. Clin Lung Cancer 2012; 13: 68-74.
115. Schernhammer ES, Giobbie-Hurder A, Gantman K, et al. A randomized controlled trial of oral melatonin supplementation and breast cancer biomarkers. Cancer Causes Control 2012; 23: 609-616.
116. Picinato MC, Hirata AE, Cipolla-Neto J, et al. Activation of insulin and IGF-1 signaling pathways by melatonin through MT1 receptor in isolated rat pancreatic islets. J Pineal Res 2008; 44: 88-94.
117. Leibowitz A, Peleg E, Sharabi Y, et al. The role of melatonin in the pathogenesis of hypertension in rats with metabolic syndrome. Am J Hypertens 2008; 21: 348-351.
118. Kitagawa A, Ohta Y, Ohashi K,. Melatonin improves metabolic syndrome induced by high fructose intake in rats. J Pineal Res 2012; 52: 403-413.
119. Cardinali DP, Bernasconi PA, Reynoso R, et al. Melatonin may curtail the metabolic syndrome: studies on initial and fully established fructose-induced metabolic syndrome in rats. Int J Mol Sci 2013; 14: 2502-2514.
120. Agil A, Rosado I, Ruiz R, et al. Melatonin improves glucose homeostasis in young Zucker diabetic fatty rats. J Pineal Res 2012; 52: 203-210.
121. Vinogradova I, Anisimov V,. Melatonin prevents the development of the metabolic syndrome in male rats exposed to different light/dark regimens. Biogerontology 2013; 14: 401-409.
122. Oxenkrug GF, Summergrad P,. Ramelteon attenutates age-associated hypertension and weight gain in spontaneously hypertensive rats. Ann N Y Acad Sci 2010; 1199: 114-120.
123. Laudon M, She M, Deng X, et al. NEU-P11, a novel melatonin agonists inhibits weight gain and improves metabolic profiles in high-fat/high-sucrose- fed rats. Sleep 2009; 32: A39.
124. She M, Deng X, Guo Z, et al. NEU-P11, a novel melatonin agonist, inhibits weight gain and improves insulin sensitivity in high-fat/high-sucrose-fed rats. Pharmacol Res 2009; 59: 248-253.
125. Agil A, Reiter RJ, Juménez-Aranda A, et al. Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats. J Pineal Res 2012; 54: 381-388.
126. Hardeland R, Madrid JA, Tan D-X, et al. Melatonin, the circadian multioscillator system and health: the need for detailed analyses of peripheral melatonin signaling. J Pineal Res 2012; 52: 139-166.
127. Hardeland R,. Melatonin in aging and disease-multiple consequences of reduced secretion, options and limits of treatment. Aging Dis 2012; 3: 194-225.
128. Peschke E, Stumpf I, Bazwinsky I, et al. Melatonin and type 2 diabetes-a possible link? J Pineal Res 2007; 42: 350-358.
129. Peschke E,. Melatonin, endocrine pancreas and diabetes. J Pineal Res 2008; 44: 26-40.
130. Cardinali DP, Cano P, Jiménez-Ortega V, et al. Melatonin and the metabolic syndrome: pathophysiologic and therapeutical implications. Neuroendocrinology 2011; 93: 133-142.
131. Nduhirabandi F, du Toit EF, Lochner A,. Melatonin and the metabolic syndrome: a tool for effective therapy in obesity-associated abnormalities? Acta Physiol (Oxf) 2012; 205: 209-223.
132. Reiter RJ, Tan D-X, Korkmaz A, et al. Obesity and metabolic syndrome: association with chronodisruption, sleep deprivation, and melatonin suppression. Ann Med 2012; 44: 564-577.
133. Srinivasan V, Ohta Y, Espino J, et al. Metabolic syndrome, its pathophysiology and the role of melatonin. Recent Pat Edocr Metab Immune Drug Discov 2013; 7: 11-25.
134. Gutierrez-Cuesta J, Tajes M, Jiménez A, et al. Evaluation of potential pro-survival pathways regulated by melatonin in a murine senescence model. J Pineal Res 2008; 45: 497-505.
135. Chang H-M, Wu U-I, Lan C-T,. Melatonin preserves longevity protein (sirtuin 1) expression in the hippocampus of total sleep-deprived rats. J Pineal Res 2009; 47: 211-220.
136. Tajes M, Gutierrez-Cuesta J, Ortuño-Sahagun D, et al. Anti-aging properties of melatonin in an in vitro murine senescence model: involvement of the sirtuin 1 pathway. J Pineal Res 2009; 47: 228-237.
137. Jung-Hynes B, Ahmad N,. SIRT1 controls circadian clock circuitry and promotes cell survival: a connection with age-related neoplasms. FASEB J 2009; 23: 2803-2809.
138. Jung-Hynes B, Reiter RJ, Ahmad N,. Sirtuins, melatonin and circadian rhythms: building a bridge between aging and cancer. J Pineal Res 2010; 48: 9-19.
139. Jung-Hynes B, Schmit TL, Reagan-Shaw SR, et al. Melatonin, a novel Sirt1 inhibitor, imparts proliferative effects against prostate cancer cells in vitro culture and in vivo in TRAMP model. J Pineal Res 2011; 50: 140-149.
140. Cheng Y, Cai L, Jiang P, et al. SIRT1 inhibition by melatonin exerts antitumor activity in human osteosarcoma cells. Eur J Pharmacol 2013; 715: 219-229.
141. Hill SM, Frasch T, Xiang S, et al. Molecular mechanisms of melatonin anticancer effects. Integr Cancer Ther 2009; 8: 337-346.
142. Lim HD, Kim YS, Ko SH, et al. Cytoprotective and anti-inflammatory effects of melatonin in hydrogen peroxide-stimulated CHON-001 human chondrocyte cell line and rabbit model of osteoarthritis via the SIRT1 pathway. J Pineal Res 2012; 53: 225-237.
143. Wang X,. The antiapoptotic activity of melatonin in neurodegenerative diseases. CNS Neurosci Ther 2009; 15: 345-357.
144. Maity P, Bindu S, Dey S, et al. Melatonin reduces indomethacin-induced gastric mucosal cell apoptosis by preventing mitochondrial oxidative stress and the activation of mitochondrial pathway of apoptosis. J Pineal Res 2009; 46: 314-323.
145. Luchetti F, Canonico B, Betti M, et al. Melatonin signaling and cell protection function. FASEB J 2010; 24: 3603-3624.
146. Tuñõn MJ, San Miguel B, Crespo I, et al. Melatonin attenuates apoptotic liver damage in fulminant hepatic failure induced by the rabbit hemorrhagic disease virus. J Pineal Res 2011; 50: 38-45.
147. Kim CH, Kim KH, Yoo YM,. Melatonin protects against apoptotic and autophagic cell death in C2C12 murine myoblast cells. J Pineal Res 2011; 50: 241-249.
148. Lanoix D, Lacasse AA, Reiter RJ, et al. Melatonin: the smart killer: the human trophoblast as a model. Mol Cell Endocrinol 2012; 348: 1-11.
149. Mohseni M, Mihandoost E, Shirazi A, et al. Melatonin may play a role in modulation of bax and bcl-2 expression levels to protect rat peripheral blood lymphocytes from gamma irradiation induced apoptosis. Mutat Res 2012; 738/739: 19-27.
150. Bejarano I, Redondo PC, Espino J, et al. Melatonin induces mitochondrial-mediated apoptosis in human myeloid HL-60 cells. J Pineal Res 2009; 46: 392-400.
151. Mediavilla MD, Sanchez-Barcelo EJ, Tan D-X, et al. Basic mechanisms involved in the anti-cancer effects of melatonin. Curr Med Chem 2010; 17: 4462-4481.
152. Mao L, Cheng Q, Guardiola-Lemaître B, et al. In vitro and in vivo antitumor activity of melatonin receptor agonists. J Pineal Res 2010; 49: 210-221.
153. Sánchez-Hidalgo M, Guerrero JM, Villegas I, et al. Melatonin, a natural programmed cell death inducer in cancer. Curr Med Chem 2012; 19: 3805-3821.
154. Rodriguez C, Martín V, Herrera F, et al. Mechanisms involved in the pro-apoptotic effect of melatonin in cancer cells. Int J Mol Sci 2013; 14: 6597-6613.
155. Tan D-X, Hardeland R, Manchester LC, et al. The changing biological roles of melatonin during evolution: from an antioxidant to signals of darkness, sexual selection and fitness. Biol Rev Camb Philos Soc 2010; 85: 607-623.
156. Asher G, Gatfield D, Stratmann M, et al. SIRT1 regulates circadian clock gene expression through PER2 deacetylation. Cell 2008; 134: 317-328.
157. Belden WJ, Dunlap JC,. SIRT1 is a circadian deacetylase for core clock components. Cell 2008; 134: 212-214.
158. +-dependent deacetylase SIRT1 modulates CLOCK-mediated chromatin remodeling and circadian control. Cell 2008; 134: 329-340.
159. Grimaldi B, Nakahata Y, Kaluzova M, et al. Chromatin remodeling, metabolism and circadian clocks: the interplay of CLOCK and SIRT1. Int J Biochem Cell Biol 2009; 41: 81-86.
160. + salvage pathway by CLOCK-SIRT1. Science 2009; 324: 654-657.
161. + biosynthesis. Science 2009; 324: 651-654.
162. Wijnen H,. Circadian rhythms. A circadian loop asSIRTs itself. Science 2009; 324: 598-599.
163. Wyse CA, Coogan AN,. Impact of aging on diurnal expression patterns of CLOCK and BMAL1 in the mouse brain. Brain Res 2010; 1337: 21-31.
164. Kondratov RV, Vykhovanets O, Kondratova AA, et al. Antioxidant N-acetyl-L-cysteine ameliorates symptoms of premature aging associated with the deficiency of the circadian protein BMAL1. Aging (Albany) 2009; 1: 979-987.
165. Gerstner JR,. The aging clock: to 'BMAL'icious toward learning and memory. Aging (Albany) 2010; 2: 251-254.
166. Somanath PR, Podrez EA, Chen J, et al. Deficiency in core circadian protein Bmal1 is associated with a prothrombotic and vascular phenotype. J Cell Physiol 2011; 226: 132-140.
167. Marcheva B, Ramsey KM, Buhr ED, et al. Disruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes. Nature 2010; 466: 627-631.
168. Kondratov RV, Kondratova AA, Gorbacheva VY, et al. Early aging and age-related pathologies in mice deficient in BMAL1, the core componentof the circadian clock. Genes Dev 2006; 20: 1868-1873.
169. Dubrovsky YV, Samsa WE, Kondratov RV,. Deficiency of circadian protein CLOCK reduces lifespan and increases age-related cataract development in mice. Aging (Albany) 2010; 2: 936-944.
170. Ha E, Yim SV, Chung JH, et al. Melatonin stimulates glucose transport via insulin receptor substrate 1/phosphatidylinositol 3-kinase pathway in C2C12 murine skeletal muscle cells. J Pineal Res 2006; 41: 67-72.
171. Shieh JM, Wu HAT, Cheng KC, et al. Melatonin ameliorates high fat diet-induced diabetes and stimulates glycogen synthesis via PKCζ-Akt- GSK3β pathway in hepatic cells. J Pineal Res 2009; 47: 339-344.
172. Yoo YM,. Melatonin-mediated insulin synthesis during endoplasmic reticulum stress involves HuD expression in rat insulinoma INS-1E cells. J Pineal Res 2013; 55: 207-220.
173. Kwon KJ, Kim HJ, Shin CY, et al. Melatonin potentiates the neuroprotective properties of resveratrol against beta-amyloid-induced neurodegeneration by modulating AMP-activated protein kinase pathways. J Clin Neurol 2010; 6: 127-137.
174. Zaouali MA, Boncompagni E, Reiter RJ, et al. AMPK involvement in endoplasmic reticulum stress and autiphagy modulation after fatty liver graft preservation: a role for melatonin and trimetazidine cocktail. J Pineal Res 2013; 55: 65-78.
175. Mendes C, Lopes AM, do Amaral FG, et al. Adaptations of the aging animal to exercise: role of daily supplementation with melatonin. J Pineal Res 2013; 55: 229-239.
176. Menassol JB, Tautou C, Collet A, et al. The effect of an intracerebroventricular injection of metformin or AICAR on the plasma concentrations of melatonin in the ewe: potential involvement of AMPK? BMC Neurosci 2011; 12: 76.
177. Gurd BJ,. Deactylation of PGC-1α by SIRT1: importance for skeletal muscle function and exercise-induced mitochondrial biogenesis. Appl Physiol Nutr Metab 2011; 36: 589-597.
178. Brenmoehl J, Hoeflich A,. Dual control of mitochondrial biogenesis by sirtuin 1 amd sirtuin 3. Mitochondrion 2013 [Epub ahaed of print, Apr 11; pii: S1567-7249(13)00065-2. doi: 10.1016/j.mito.2013.04.002 ].
179. González-Sánchez E, Martín-Caballero J, Flores JM, et al. Lkb1 loss promotes tumor progression of BRAF(V600E)-induced lung adenomas. PLoS ONE 2013; 8: e66933.
180. Ekizoglu S, Dalay N, Karaman E, et al. LKB1 downregulation may be independent of promoter methylation of FOXO3 expression in head and neck cancer. Transl Res 2013; 162: 122-129.
181. Randy LH, Guoying B,. Agonism for peroxisosme proliferator receptor-γ may have therapeutic potential for neuroinflammation and Parkinson's Disease. Curr Neuropharmacol 2007; 5: 35-46.
182. Das UN,. A defect in the activity of Delta6 and Delta5 desaturases may be a factor predisposing to the development of insulin resistance syndrome. Prostaglandins Leukot Essent Fatty Acids 2005; 72: 343-350.
183. Mendoza J, Graff C, Dardente H, et al. Feeding cues alter clock gene oscillations and photic responses in the suprachiasmatic nuclei of mice exposed to a light/dark cycle. J Neurosci 2005; 25: 1514-1522.
184. Zanquetta MM, Seraphim PM, Sumida DH, et al. Calorie restriction reduces pinealectomy-induced insulin resistance by improving GLUT4 gene expression and its translocation to the plasma membrane. J Pineal Res 2003; 35: 141-148.
185. Mattison JA, Lane MA, Roth GS, et al. Calorie restriction in rhesus monkeys. Exp Gerontol 2003; 38: 35-46.
186. Sethi S, Radio NM, Kotlarczyk MP, et al. Determination of the minimal melatonin exposure required to induce osteoblast differentiation from human mesenchymal stem cells and these effects on downstream signaling pathways. J Pineal Res 2010; 49: 222-238.
187. Zhang L, Su P, Xu C, et al. Melatonin inhibits adipogenesis and enhances osteogenesis of human mesenchymal stem cells by suppressing PPARγ expression and enhancing Rux2 expression. J Pineal Res 2010; 49: 364-372.
188. Kennaway DJ, Owens JA, Voultsios A, et al. Adipokines and adipocyte function in Clock mutant mice that retain melatonin rhythmicity. Obesity (Silver Spring) 2012; 20: 295-305.
189. Alonso-Vale MIC, Peres SB, Vernochet C, et al. Adipocyte differentiation is inhibited by melatonin through the regulation of C/EBPβ transcriptional activity. J Pineal Res 2009; 47: 221-227.
190. González A, Alvarez-García V, Martínez-Campa C, et al. Melatonin promotes differentiation of 3T3-L1 fibroblasts. J Pineal Res 2012; 52: 12-20.
191. Hardeland R,. Melatonin: signaling mechanisms of a pleiotropic agent. BioFactors 2009; 35: 183-192.
192. Niles LP, Pan Y, Kang S, et al. Melatonin induces histone hyperacetylation in the rat brain. Neurosci Lett 2013; 541: 49-53.
193. Proietti S, Cucina A, D'Anselmi F, et al. Melatonin and vitamin D3 synergistically down-regulate Akt and MDM2 leading to TGFβ-1-dependent growth inhibition of breast cancer cells. J Pineal Res 2011; 50: 150-158.
194. Fan L, Sun G, Ma T, et al. Melatonin reverses tunicamycin-induced endoplasmic reticulum stress in human hepatocellular carcinoma cells and improves cytotoxic response to doxorubicin by increasing CHOP and decreasing Survivin. J Pineal Res 2013; 55: 184-194.
195. Kimball SR, Abbas A, Jefferson LS,. Melatonin represses oxidative stress-induced activation of the MAP kinase and mTOR signaling pathways in H411E hepatoma cells through inhibition of Ras. J Pineal Res 2008; 44: 379-386.
196. Min KJ, Jang JH, Kwon TK,. Inhibitory effects of melatonin on the lipopolysaccharide-induced CC chemokine expression in BV2 murine microglial
197. Xia MZ, Liang XL, Wang H, et al. Melatonin modulates TLR4-mediated inflammatory genes through MyD88- and TRIF-dependent signaling pathways in lipopolysaccharide-stimulated RAW264.7 cells. J Pineal Res 2012; 53: 325-334.
198. Imbezi M, Uz T, Dzitoyeva S, et al. Melatonin signaling in mouse cerebellar granule cells with variable MT1 and MT2 melatonin receptors. Brain Res 2008; 1227: 19-25.
199. Kong PJ, Byun JS, Lim SY, et al. Melatonin induces Akt phosphorylation through melatonin receptor- and PI3K-dependent pathways in primary astrocytes. Korean J Physiol Pharmacol 2008; 12: 37-41.
200. Faria JA, Kinote A, Ignacio-Souza LM, et al. Melatonin acts through MT1/MT2 receptors to activate hypothalamic AKT and suppress hepatic gluconeogenesis. Am J Physiol Endocrinol Metab 2013; 305: E230-E242.
201. Lee SH, Chun W, Kong PJ, et al. Sustained activation of Akt by melatonin contributes to the protection against kainic acid-induced neuronal death in hippocampus. J Pineal Res 2006; 40: 79-85.
202. Koh PO,. Melatonin prevents the injury-induced decline of Akt/forkhead transcription factors phosphorylation. J Pineal Res 2008; 45: 199-203.
203. Kilic U, Yilmaz B, Reiter RJ, et al. Effects of memantine and melatonin on signal transduction pathways vascular leakage and brain injury after focal cerebral ischemia in mice. Neuroscience 2013; 237: 268-276.
204. Kilic U, Kilic E, Reiter RJ, et al. Signal transduction pathways involved in melatonin-induced neuroprotection after focal cerebral ischemia in mice. J Pineal Res 2005; 38: 67-71.
205. Kilic E, Kilic U, Reiter RJ, et al. Tissue-plasminogen activator-induced ischemic brain injury is reversed by melatonin: role of iNOS and Akt. J Pineal Res 2005; 39: 151-155.
206. Bai J, Dong L, Song Z, et al. The role of melatonin as an antioxidant in human lens epithelial cells. Free Radic Res 2013; 47: 635-642.
207. Kim CH, Yoo YM,. Fluid shear stress and melatonin in combination activate anabolic proteins in MC3T3-E1 osteoblast cells. J Pineal Res 2013; 55: 453-461.
208. Alonso-Vale MIC, Andreotti A, Peres SB, et al. Melatonin enhances leptin expression by rat adipocytes in the presence of insulin. Am J Physiol Endocrinol Metab 2005; 288: E805-E812.
209. Hsu JT, Kuo CJ, Chen TH, et al. Melatonin prevents hemorrhagic shock-induced liver injury in rats through an Akt-dependent HO-1 pathway. J Pineal Res 2012; 53: 410-416.
210. Koh PO,. Melatonin prevents hepatic injury-induced decrease in Akt downstream targets phosphorylations. J Pineal Res 2011; 51: 214-219.
211. Jiang T, Chang Q, Zhao Z, et al. Melatonin-mediated cytoprotection against hyperglycemic injury in Müller cells. PLoS ONE 2012; 7: e50661.
212. Sartori C, Dessen P, Mathieu C, et al. Melatonin improves glucose homeostasis and endothelial vascular function in high-fat diet-fed insulin-resistant mice. Endocrinology 2009; 150: 5311-5317.
213. Nduhirabandi F, du Toit EF, Blackhurst D, et al. Chronic melatonin consumption prevents obesity-related metabolic abnormalities and protects the heart against myocardial ischemia and reperfusion injury in a prediabetic model of diet-induced obesity. J Pineal Res 2011; 50: 171-182.
214. Genade S, Genis A, Ytrehus K, et al. Melatonin receptor-mediated protection against myocardial ischaemia/reperfusion injury: role of its anti-adrenergic actions. J Pineal Res 2008; 45: 449-458.
215. Kanki T, Nakayama H, Sasaki N, et al. Mitochondrial nucleoid and transcription factor A. Ann N Y Acad Sci 2004; 1011: 61-68.
216. Ekstrand MI, Falkenberg M, Rantanen A, et al. Mitochondrial transcription factor A regulates mtDNA copy number in mammals. Hum Mol Genet 2004; 13: 935-944.
217. Kang D, Hamasaki N,. Mitochondrial transcription factor A in the maintenance of mitochondrial DNA: overview of its multiple roles. Ann N Y Acad Sci 2005; 1042: 101-108.
218. Kienhöfer J, Häussler DJ, Ruckelshausen F, et al. Association of mitochondrial antioxidant enzymes with mitochondrial DNA as integral nucleoid constituents. FASEB J 2009; 23: 2034-2044.
219. Fukui H, Moraes CT,. The mitochondrial impairment, oxidative stress and neurodegeneration connection: reality or just an attractive hypothesis? Trends Neurosci 2008; 31: 251-256.
220. Thompson LV,. Oxidative stress, mitochondria and mtDNA-mutator mice. Exp Gerontol 2006; 41: 1220-1222.
221. Hardeland R, Poeggeler B, Pappolla MA,. Mitochondrial actions of melatonin-an endeavor to identify their adaptive and cytoprotective mechanisms. Abh Sächs Akad Wiss Math-Nat Kl, Endokrinologie Pt 4, 2009; 65: 14-31.
222. Hardeland R,. Melatonin, mitochondrial electron flux and leakage: recent findings and resolution of contradictory results. Adv Stud Biol 2009; 1: 207-230.
223. Hardeland R,. Antioxidative protection by melatonin-multiplicity of mechanisms from radical detoxification to radical avoidance. Endocrine 2005; 27: 119-130.
224. Boveris A, Alvarez S, Navarro A,. The role of mitochondrial nitric oxide synthase in inflammation and septic shock. Free Radic Biol Med 2002; 33: 1186-1193.
225. Escames G, Acuña-Castroviejo D, Lõpez LC, et al. Pharmacological utility of melatonin in the treatment of septic shock: experimental and clinical evidence J Pharm Pharmacol 2006; 58: 1153-1165.
226. Alvarez S, Evelson PA,. Nitric oxide and oxygen metabolism in inflammatory conditions: sepsis and exposition to polluted ambients. Front Biosci 2007; 12: 964-974.
227. Brown GC, Bal-Price A,. Inflammatory neurodegeneration mediated by nitric oxide, glutamate, and mitochondria. Mol Neurobiol 2003; 27: 325-355.
228. Dahm CC, Moore K, Murphy MP,. Persistent S-nitrosation of complex I and other mitochondrial membrane proteins by S-nitrosothiols but not nitric oxide or peroxynitrite: implications for the interaction of nitric oxide with mitochondria. J Biol Chem 2006; 281: 10056-10065.
229. Radi R, Cassina A, Hodara R, et al. Peroxynitrite reactions and formation in mitochondria. Free Radic Biol Med 2002; 33: 1451-1464.
230. Trujillo M, Folkes L, Bartesaghi S, et al. Peroxynitrite-derived carbonate and nitrogen dioxide radicals readily react with lipoic and dihydrolipoic acid. Free Radic Biol Med 2005; 39: 279-288.
231. Ferrer-Sueta G, Radi R,. Chemical biology of peroxynitrite: kinetics, diffusion, and radicals. ACS Chem Biol 2009; 4: 161-177.
232. Hardeland R,. Melatonin and its metabolites as anti-nitrosating and anti-nitrating agents. J Exp Integr Med 2011; 1: 67-81.
233. Klingen AR, Palsdottir H, Hunte C, et al. Redox-linked protonation state changes in cytochrome bc1 identified by Poisson-Boltzmann electrostatics calculations. Biochim Biophys Acta 2007; 1767: 204-221.
234. Lesnefsky EJ, Hoppel CL,. Cardiolipin as an oxidative target in cardiac mitochondria in the aged rat. Biochim Biophys Acta 2008; 1777: 1020-1027.
235. Lesnefsky EJ, Minkler P, Hoppel CL,. Enhanced modification of cardiolipin during ischemia in the aged heart. J Mol Cell Cardiol 2009; 46: 1008-1015.
236. 1 complex catalysis and supercomplex formation. Biochim Biophys Acta 2009; 1787: 609-616.
237. Petrosillo G, Matera M, Moro N, et al. Mitochondrial complex I dysfunction in rat heart with aging: critical role of reactive oxygen species and cardiolipin. Free Radic Biol Med 2009; 46: 88-94.
238. Basova LV, Kurnikov IV, Wang L, et al. Cardiolipin switch in mitochondria: shutting off the reduction of cytochrome c and turning on the peroxidase activity. Biochemistry 2007; 46: 3423-3434.
239. Ott M, Gogvadze V, Orrenius S, et al. Mitochondria, oxidative stress and cell death. Apoptosis 2007; 12: 913-922.
240. Bayir H, Tyurin VA, Tyurina YY, et al. Selective early cardiolipin peroxidation after traumatic brain injury: an oxidative lipidomics analysis. Ann Neurol 2007; 62: 154-169.
241. Kagan VE, Bayir A, Bayir H, et al. Mitochondria-targeted disruptors and inhibitors of cytochrome c/cardiolipin peroxidase complexes: a new strategy in anti-apoptotic drug discovery. Mol Nutr Food Res 2009; 53: 104-114.
242. Kagan VE, Bayir HA, Belikova NA, et al. Cytochrome c/cardiolipin relations in mitochondria: a kiss of death. Free Radic Biol Med 2009; 46: 1439-1453.
243. Samhan-Arias AK, Tyurina YY, Kagan VE,. Lipid antioxidants: free radical scavenging versus regulation of enzymatic lipid peroxidation. J Clin Biochem Nutr 2011; 48: 91-95.
244. Ji J, Kline AE, Amoscato A, et al. Lipidomics indentifies cardiolipin oxidation as a mitochondrial target for redox therapy of brain injury. Nat Neurosci 2012; 15: 1407-1413.
245. Kagan VE,. Emerging free radical optimism: translational oxidative lipidomics. Eur J Clin Invest 2013; 43 (Suppl 1): 57.
246. Petrosillo G, Di Venosa N, Pistolese M, et al. Protective effect of melatonin against mitochondrial dysfunction associated with cardiac ischemia-reperfusion: role of cardiolipin. FASEB J 2006; 20: 269-276.
247. Luchetti F, Canonico B, Mannello F, et al. Melatonin reduces early changes in intramitochondrial cardiolipin during apoptosis in U937 cell line. Toxicol In Vitro 2007; 21: 293-301.
248. Petrosillo G, Fattoretti P, Matera M, et al. Melatonin prevents age-related mitochondrial dysfunction in rat brain via cardiolipin protection. Rejuvenation Res 2008; 11: 935-943.
249. 2+, and lipid insults in NARP cybrids: a potential therapeutic target for melatonin. J Pineal Res 2012; 52: 93-106.
250. Wakatsuki A, Okatani Y, Shinohara K, et al. Melatonin protects fetal rat brain against oxidative mitochondrial damage. J Pineal Res 2001; 30: 22-28.
251. Reiter RJ, Acuña-Castroviejo D, Tan DX, et al. Free radical-mediated molecular damage. Mechanisms for the protective actions of melatonin in the central nervous system. Ann N Y Acad Sci 2001; 939: 200-215.
252. Okatani Y, Wakatsuki A, Reiter RJ, et al. Protective effect of melatonin against mitochondrial injury induced by ischemia and reperfusion of rat liver. Eur J Pharmacol 2003; 469: 145-152.
253. Acuña-Castroviejo D, Escames G, Rodríguez MI, et al. Melatonin role in the mitochondrial function. Front Biosci 2007; 12: 947-963.
254. Reiter RJ, Tan D-X, Manchester LC, et al. Melatonin reduces oxidant damage and promotes mitochondrial respiration: implications for aging. Ann N Y Acad Sci 2002; 959: 238-250.
255. Rodríguez MI, Carretero M, Escames G, et al. Chronic melatonin treatment prevents age-dependent cardiac mitochondrial dysfunction in senescence-accelerated mice. Free Radic Res 2007; 41: 15-24.
256. Rodriguez MI, Escames G, Lõpez LC, et al. Melatonin administration prevents cardiac and diaphragmatic mitochondrial oxidative damage in senescence-accelerated mice. J Endocrinol 2007; 194: 637-643.
257. Liang H, Ran Q, Jang YC, et al. Glutathione peroxidase 4 differentially regulates the release of apoptogenic proteins from mitochondria. Free Radic Biol Med 2009; 47: 312-320.
258. Kim SC, Sprung R, Chen Y, et al. Substrate and functional diversity of lysine acetylation revealed by a proteomics survey. Mol Cell 2006; 23: 607-618.
259. Schlicker C, Gertz M, Papatheodorou P, et al. Substrates and regulation mechanisms for the human mitochondrial sirtuins Sirt3 and Sirt5. J Mol Biol 2008; 382: 790-801.
260. Staniek K, Gille L, Kozlov AV, et al. Mitochondrial superoxide radical formation is controlled by electron bifurcation to the high and low potential pathways. Free Radic Res 2002; 36: 381-387.
261. Gong X, Yu L, Xia D, et al. Evidence for electron equilibrium between the two hemes bL in the dimeric cytochrome bc1 complex. J Biol Chem 2005; 280: 9251-9257.
262. Dungel P, Mittermayr R, Haindl S, et al. Illumination with blue light reactivates respiratory activity of mitochondria inhibited by nitric oxide, but not by glycerol trinitrate. Arch Biochem Biophys 2008; 471: 109-115.
263. Wang W, Fang H, Groom L, et al. Superoxide flashes in single mitochondria. Cell 2008; 134: 279-290.
264. Sheu SS, Wang W, Cheng H, et al. Superoxide flashes: illuminating new insights into cardiac ischemia/reperfusion injury. Future Cardiol 2008; 4: 551-554.
265. 2+ stress in astrocyte. J Pineal Res 2011; 50: 427-435.
266. 2+- mediated permeability transition and beyond in rat brain astrocytes. J Pineal Res 2010; 48: 20-38.
267. Andrabi SA, Sayeed I, Siemen D, et al. Direct inhibition of the mitochondrial permeability transition pore: a possible mechanism responsible for anti-apoptotic effects of melatonin. FASEB J 2004; 18: 869-871.
268. Lõpez A, García JA, Escames G, et al. Melatonin protects the mitochondria from oxidative damage reducing oxygen consumption, membrane potential, and superoxide anion production. J Pineal Res 2009; 46: 188-198.
269. Paradies G, Petrosillo G, Paradies V, et al. Melatonin, cardiolipin and mitochondrial bioenergetics in health and disease. J Pineal Res 2010; 48: 297-310.
270. Venegas C, García JA, Escames G, et al. Extrapineal melatonin: analysis of its subcellular distribution and daily fluctuations. J Pineal Res 2012; 52: 217-227.
271. Messner M, Hardeland R, Rodenbeck A, et al. Tissue retention and subcellular distribution of continuously infused melatonin in rats under near physiological conditions. J Pineal Res 1998; 25: 251-259.
272. Iñarrea P, Casanova A, Alava MA, et al. Melatonin and steroid hormones activate Cu,Zn-superoxide dismutase by means of mitochondrial cytrochrome P450. Free Radic Biol Med 2011; 50: 1575-1581.
273. Iñarrea P, Moini H, Han D, et al. Mitochondrial respiratory chain and thioredoxin reductase regulate intermembrane Cu,Zn-superoxide dismutase activity: implications for mitochondrial energy metabolism and apoptosis. Biochem J 2007; 405: 173-179.
274. Reyes-Toso CF, Ricci CR, de Mignone IR, et al. In vitro effect of melatonin on oxygen consumption in liver mitochondria of rats. Neuro Endocrinol Lett 2003; 24: 341-344.
275. Reyes-Toso CF, Rebagliati IR, Ricci CR, et al. Effect of melatonin treatment on oxygen consumption by rat liver mitochondria. Amino Acids 2006; 31: 299-302.
276. Rakhit RD, Mojet MH, Marber MS, et al. Mitochondria as targets for nitric oxide-induced protection during simulated ischemia and reoxygenation in isolated neonatal cardiomyocytes. Circulation 2001; 103: 2617-2623.
277. Acuña-Castroviejo D, Escames G, Carazo A, et al. Melatonin, mitochondrial homeostasis and mitochondrial-related diseases. Curr Top Med Chem 2002; 2: 133-151.
278. Acuña-Castroviejo D, Escames G, Leõn J, et al. Mitochondrial regulation by melatonin and its metabolites. Adv Exp Med Biol 2003; 527: 549-557.
279. Reiter RJ, Paredes SD, Korkmaz A, et al. Melatonin combats molecular terrorism at the mitochondrial level. Interdiscipl Toxicol 2008; 1: 137-149.
280. Escames G, Lõpez A, García JA, et al. The role of mitochondria in brain aging and the effects of melatonin. Curr Neuropharmacol 2010; 8: 182-193.
281. Srinivasan V, Spence DW, Pandi-Perumal SR, et al. Melatonin in mitochondrial dysfunction and related disorders. Int J Alzheimers Dis 2011; 2011: 326320.
282. Acuña-Castroviejo D, Lõpez LC, Escames G, et al. Melatonin-mitochondria interplay in health and disease. Curr Top Med Chem 2011; 11: 221-240.
283. Cardinali DP, Pagano ES, Scacchi Bernasconi PA, et al. Melatonin and mitochondrial dysfunction in the central nervous system. Horm Behav 2013; 63: 322-330.
284. Feng YM, Jia YF, Su LY, et al. Decreased mitochondrial DNA copy number in the hippocampus and peripheral blood during opiate addiction is mediated by autophagy and can be salvaged by melatonin. Autophagy 2013; 9: 18-29.
285. Chang CF, Huang HJ, Lee HC, et al. Melatonin attenuates kainic acid-induced neurotoxicity in mouse hippocampus via inhibition of autophagy and α-synuclein aggregation. J Pineal Res 2012; 52: 312-321.
286. Osseni RA, Rat P, Bogdan A, et al. Evidence of prooxidant and antioxidant action of melatonin on human liver cell line HepG2. Life Sci 2000; 68: 387-399.
287. Cos S, Mediavilla MD, Fernández R, et al. Does melatonin induce apoptosis in MCF-7 human breast cancer cells in vitro? J Pineal Res 2002; 32: 90-96.
288. Albertini MC, Radogna F, Accorsi A, et al. Intracellular pro-oxidant activity of melatonin deprives U937 cells of reduced glutathione without affecting glutathione peroxidase activity. Ann N Y Acad Sci 2006; 1091: 10-16.
289. Martín-Renedo J, Mauriz JL, Jorquera F, et al. Melatonin induces cell cycle arrest and apoptosis in hepatocarcinoma HepG2 cell line. J Pineal Res 2008; 45: 532-540.
290. Cucina A, Proietti S, D'Anselmi F, et al. Evidence for a biphasic apoptotic pathway induced by melatonin in MCF-7 breast cancer cells. J Pineal Res 2009; 46: 172-180.
291. Gonzalez A, del Castillo-Vaguero A, Miro-Moran A, et al. Melatonin reduces pancreatic tumor cell viability by altering mitochondrial physiology. J Pineal Res 2011; 50: 250-260.
292. Bejarano I, Espino J, Barriga C, et al. Pro-oxidant effect of melatonin in tumor leucocytes: relation with its cytotoxic and pro-apoptotic effects. Basic Clin Pharmacol Toxicol 2011; 108: 14-20.
293. Bonmati-Carrion MA, Alvarez-Sanchez N, Hardeland R, et al. A comparison of B16 melanoma cells and 3T3 fibroblasts concerning cell viability and ROS production in the presence of melatonin, tested over a wide range of concentrations. Int J Mol Sci 2013; 14: 3901-3920.
294. Perdomo J, Cabrera J, Estévez F, et al. Melatonin induces apoptosis through a caspase-dependent but reactive oxygen species-independent mechanism in human leukemia Molt-3 cells. J Pineal Res 2013; 55: 195-206.
295. Zhang HM, Zhang Y, Zhang BX,. The role of mitochondrial complex III in melatonin-induced ROS production in cultured mesangial cells. J Pineal Res 2011; 50: 78-82.
296. Ames BN, Shigenaga MK, Hagen TM,. Mitochondrial decay in aging. Biochim Biophys Acta 1995; 1271: 165-170.
297. Terzioglu M, Larsson NG,. Mitochondrial dysfunction in mammalian ageing. Novartis Found Symp 2007; 287: 197-208.
298. Figueiredo PA, Mota MP, Appell HJ, et al. The role of mitochondria in aging of skeletal muscle. Biogerontology 2008; 9: 67-84.
299. Fannin SW, Lesnefsky EJ, Slabe TJ, et al. Aging selectively decreases oxidative capacity in rat heart interfibrillar mitochondria. Arch Biochem Biophys 1999; 372: 399-407.
300. Lesnefsky EJ, Gudz TI, Moghaddas S, et al. Aging decreases electron transport complex III activity in heart interfibrillar mitochondria by alteration of the cytochrome c binding site. J Mol Cell Cardiol 2001; 33: 37-47.
301. Hoppel CL, Moghaddas S, Lesnefsky EJ,. Interfibrillar cardiac mitochondrial complex III defects in the aging rat heart. Biogerontology 2002; 3: 41-44.
302. Moghaddas S, Stoll MS, Minkler PE, et al. Preservation of cardiolipin content during aging in rat heart interfibrillar mitochondria. J Gerontol A Biol Sci Med Sci 2002; 57: B22-B28.
303. O site of complex III augments oxyradical production in rat heart interfibrillar mitochondria. Arch Biochem Biophys 2003; 414: 59-66.
304. 2+-induced permeability transition and cytochrome c release in rat heart mitochondria with aging: effect of melatonin. J Pineal Res 2010; 48: 340-346.
305. Öztürk G, Akbulut KG, Güney S, et al. Age-related changes in the rat brain mitochondrial antioxidative enzyme ratios: modulation by melatonin. Exp Gerontol 2012; 47: 706-711.
306. Srinivasan V, Pandi-Perumal SR, Cardinali DP, et al. Melatonin in Alzheimer's disease and other neurodegenerative disorders. Behav Brain Funct 2006; 2: 15.
307. Dragicevic N, Copes N, O'Neal-Moffit G, et al. Melatonin treatment restores mitochondrial function in Alzheimer's mice: a mitochondrial protective role of melatonin receptor signaling. J Pineal Res 2011; 51: 75-86.
308. Rosales-Corral S, Acuña-Castroviejo D, Tan D-X, et al. Accumulation of exogenous amyloid-beta peptide in hippocampal mitochondria causes their dysfunction: a protective role for melatonin. Oxid Med Cell Longev 2012; 2012: 843649.
309. Liu Y, He J, Ji S, et al. Comparative studies of early liver dysfunction in senescence-accelerated mouse using mitochondrial proteomics approaches. Mol Cell Proteomics 2008; 7: 1737-1747.
310. Okatani Y, Wakatsuki A, Reiter RJ, et al. Acutely administered melatonin restores hepatic mitochondrial physiology in old mice. Int J Biochem Cell Biol 2003; 35: 367-375.
311. Nishikawa T, Takahashi JA, Fujibayashi Y, et al. An early stage mechanism of the age-associated mitochondrial dysfunction in the brain of SAMP8 mice; an age-associated neurodegeneration animal model. Neurosci Lett 1998; 254: 69-72.
312. Omata N, Murata T, Fujibayashi Y, et al. Age-related changes in energy production in fresh senescence-accelerated mouse brain slices as revealed by positron autoradiography. Dement Geriatr Cogn Disord 2001; 12: 78-84.
313. Boveris A, Navarro A,. Brain mitochondrial dysfunction in aging. IUBMB Life 2008; 60: 308-314.
314. Tomobe K, Nomura Y,. Neurochemistry, neuropathology, and heredity in SAMP8: a mouse model of senescence. Neurochem Res 2009; 34: 660-669.
315. Carretero M, Escames G, Lõpez LC, et al. Long-term melatonin administration protects brain mitochondria from aging. J Pineal Res 2009; 47: 192-200.
316. Okatani Y, Wakatsuki A, Reiter RJ,. Melatonin protects hepatic mitochondrial respiratory chain activity in senescence-accelerated mice. J Pineal Res 2002; 32: 143-148.
317. Okatani Y, Wakatsuki A, Reiter RJ, et al. Hepatic mitochondrial dysfunction in senescence-accelerated mice: correction by long-term, orally administered physiological levels of melatonin. J Pineal Res 2002; 33: 127-133.
318. Acuña-Castroviejo D, Carretero M, Doerrier C, et al. Melatonin protects lung mitochondria from aging. Age (Dordr) 2012; 34: 681-692.
319. García JJ, Piñol-Ripoll G, Martínez-Ballarín E, et al. Melatonin reduces membrane regidity and oxidative damage in the brain of SAMP8 mice. Neurobiol Aging 2011; 32: 2045-2054.
320. Cristòfol R, Porquet D, Corpas R, et al. Neurons from senescence-accelerated SAMP8 mice are protected against frailty by the sirtuin 1 promoting agents melatonin and resveratrol. J Pineal Res 2012; 52: 271-281.
321. Cuesta S, Kireev R, García C, et al. Melatonin can improve insulin resistance and aging-induced pancreas alterations in senescence-accelerated prone male mice (SAMP8). Age (Dordr) 2013; 35: 659-671.
322. Cheng S, Ma C, Qu H, et al. Differential effects of melatonin on hippocampal neurodegeneration in different aged accelerated senescence prone mouse-8. Neuro Endocrinol Lett 2008; 29: 91-99.
323. De la Fuente M,. Effects of antioxidants on immune system ageing. Eur J Clin Nutr 2002; 56 (Suppl 3): S5-S8.
324. Franceschi C, Bonafè M,. Centenarians as a model for healthy aging. Biochem Soc Trans 2003; 31: 457-461.
325. DelaRosa O, Pawelec G, Peralbo R, et al. Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology 2006; 7: 471-481.
326. Strindhall J, Nilsson BO, Löfgren S, et al. No Immune Risk Profile among individuals who reach 100 years of age: findings from the Swedish NONA immune longitudinal study. Exp Gerontol 2007; 42: 753-761.
327. Ponnappan S, Ponnappan U,. Aging and immune function: molecular mechanisms to interventions. Antioxid Redox Signal 2011; 14: 1551-1585.
328. Pfister G, Savino W,. Can the immune system still be efficient in the elderly? An immunological and immunoendocrine therapeutic perspective. Neuroimmunomodulation 2008; 15: 351-364.
329. Listi F, Candore G, Modica MA, et al. A study of serum immunoglobin levels in elderly persons that provides new insights into B cell immunosenescence. Ann N Y Acad Sci 2006; 1089: 487-495.
330. Colonna-Romano G, Buffa S, Bulati M, et al. B cells compartment in centenarian offspring and old people. Curr Pharm Des 2010; 16: 604-608.
331. Franceschi C, Monti D, Barbieri D, et al. Successful immunosenescence and the remodelling of immune responses with ageing. Nephrol Dial Transplant 1996; 11 (Suppl 9): 18-25.
332. Ginaldi L, De Martinis M, D'Ostillo A, et al. Immunological changes in the elderly. Aging (Milano) 1999; 11: 281-286.
333. Pinti M, Nasi M, Lugli E, et al. T cell homeostasis in centenarians: from the thymus to the periphery. Curr Pharm Des 2010; 16: 597-603.
334. Gayoso I, Sanchez-Correa B, Campos C, et al. Immunosenescence of human natural killer cells. J Innate Immun 2011; 3: 337-343.
335. Dewan SK, Zheng SB, Xia SJ, et al. Senescent remodeling of the immune system and its contribution to the predisposition of the elderly to infections. Chin Med J (Engl) 2012; 125: 3325-3331.
336. Mocchegiani E, Giacconi R, Muti R, et al. Zinc-bound metallothioneins and immune plasticity: lessons from very old mice and humans. Immun Ageing 2007; 4: 7.
337. Mocchegiani E, Giacconi R, Cipriano C, et al. NK and NKT cells in aging and longevity: role of zinc and metallothioneins. J Clin Immunol 2009; 29: 416-425.
338. + cells in humans. Mech Ageing Dev 2006; 127: 560-566.
339. - B cells in centenarian offspring and elderly people. Age (Dordr) 2012 [Epub ahead of print, Nov 7; doi: 10.1007/s11357-012-9488-5 ].
340. Guerrero JM, Reiter RJ,. Melatonin-immune system relationships. Curr Top Med Chem 2002; 2: 167-179.
341. Carrillo-Vico A, Guerrero JM, Lardone PJ, et al. A review of the multiple actions of melatonin on the immune system. Endocrine 2005; 27: 189-200.
342. Carrillo-Vico A, Reiter RJ, Lardone PJ, et al. The modulatory role of melatonin on immune responsiveness. Curr Opin Investig Drugs 2006; 7: 423-431.
343. Szczepanik M,. Melatonin and its influence on immune system. J Physiol Pharmacol 2007; 58 (Suppl 6): 115-124.
344. Cardinali DP, Esquifino AI, Srinivasan V, et al. Melatonin and the immune system in aging. NeuroImmunoModulation 2008; 15: 272-278.
345. Carrillo-Vico A, Lardone PJ, Álvarez-Sánchez N, et al. Melatonin: buffering the immune system. Int J Mol Sci 2013; 14: 8638-8683.
346. Lardone PJ, Carrillo-Vico A, Molinero P, et al. A novel interplay between membrane and nuclear melatonin receptors in human lymphocytes: significance in IL-2 production. Cell Mol Life Sci 2009; 66: 516-525.
347. Morrey KM, McLachlan JA, Serkin CD, et al. Activation of human monocytes by the pineal hormone melatonin. J Immunol 1994; 153: 2671-2680.
348. Castrillõn P, Cardinali DP, Pazo D, et al. Effect of superior cervical ganglionectomy on 24-h variations in hormone secretion from anterior hypophysis and in hypothalamic monoamine turnover, during the preclinical phase of Freund's adjuvant arthritis in rats. J Neuroendocrinol 2001; 13: 288-295.
349. Barjavel MJ, Mamdouh Z, Raghbate N, et al. Differential expression of the melatonin receptor in human monocytes. J Immunol 1998; 160: 1191-1197.
350. García-Mauriño S, Pozo D, Carrillo-Vico A, et al. Melatonin activates Th1 lymphocytes by increasing IL-12 production. Life Sci 1999; 65: 2143-2150.
351. + T cells but failed to stimulate LPS primed B cells. Clin Exp Immunol 2001; 124: 414-422.
352. Černyšiov V, Gerasimčik N, Mauricas M, et al. Regulation of T-cell-independent and T-cell-dependent antibody production by circadian rhythm and melatonin. Int Immunol 2010; 22: 25-34.
353. Shaji AV, Kulkarni SK, Agrewala JN,. Regulation of secretion of IL-4 and IgG1 isotype by melatonin-stimulated ovalbumin-specific T cells. Clin Exp Immunol 1998; 111: 181-185.
354. Liu F, Ng TB, Fung MC,. Pineal indoles stimulate the gene expression of immunomodulating cytokines. J Neural Transm 2001; 108: 397-405.
355. Drazen DL, Nelson RJ,. Melatonin receptor subtype mt2 (mel 1b) and not mt1 (mel 1a) is associated with melatonin-induced enhancement of cell-mediated and humoral immunity. Neuroendocrinology 2001; 74: 178-184.
356. Rai S, Haldar C, Singh SS,. Trade-off between L-thyroxin and melatonin in immune regulation of the Indian palm squirrel, Funambulus pennanti during the reproductively inactive phase. Neuroendocrinology 2005; 82: 103-110.
357. Ahmad R, Haldar C, Gupta S,. Melatonin receptor type MT1 modulates cell-mediated immunity in the seasonally breeding tropical rodent Funambulus pennanti. NeuroImmunoModulation 2012; 19: 50-59.
358. Molinero P, Soutto M, Benot S, et al. Melatonin is responsible for the nocturnal increase observed in serum and thymus of thymosin α1 and thymulin concentrations: observations in rats and humans. J Neuroimmunol 2000; 103: 180-188.
359. Hardeland R,. Neurobiology, pathophysiology, and treatment of melatonin deficiency and dysfunction. ScientificWorldJournal 2012; 2012: 640389.
360. Kang JW, Koh EJ, Lee SM,. Melatonin protects liver against ischemia and reperfusion injury through inhibition of toll-like receptor signaling pathway. J Pineal Res 2011; 50: 403-411.
361. Yip HK, Chang YC, Wallace CG, et al. Melatonin treatment improves adipose-derived mesenchymal stem cell therapy for acute lung ischemia-reperfusion injury. J Pineal Res 2013; 54: 207-221.
362. Tsai MC, Chen WJ, Tsai MS, et al. Melatonin attenuates brain contusion-induced oxidative insult, inactivation of signal transducers and activators of transcription 1, and upregulation of suppressor of cytokine signaling-3 in rats. J Pineal Res 2011; 51: 233-245.
363. Yang FL, Subeq YM, Lee CJ, et al. Melatonin ameliorates hemorrhagic shock-induced organ damage in rats. J Surg Res 2011; 167: 315-321.
364. Mei Q, Yu JP, Xu JM, et al. Melatonin reduces colon immunological injury in rats by regulating activity of macrophages. Acta Pharmacol Sin 2002; 23: 882-886.
365. Jung KH, Hong SW, Zheng HM, et al. Melatonin ameliorates cerulein-induced pancreatitis by the modulation of nuclear erythroid 2-related factor 2 and nuclear factor-kappaB in rats. J Pineal Res 2010; 48: 239-250.
366. Tyagi E, Agrawal R, Nath C, et al. Effect of melatonin on neuroinflammation and acetylcholinesterase activity induced by LPS in rat brain. Eur J Pharmacol 2010; 640: 206-210.
367. Escames G, Lõpez LC, Tapias V, et al. Melatonin counteracts inducible mitochondrial nitric oxide synthase-dependent mitochondrial dysfunction in skeletal muscle of septic mice. J Pineal Res 2006; 40: 71-78.
368. Lõpez LC, Escames G, Ortiz F, et al. Melatonin restores the mitochondrial production of ATP in septic mice. Neuro Endocrinol Lett 2006; 27: 623-630.
369. Lõpez LC, Escames G, Tapias V, et al. Identification of an inducible nitric oxide synthase in diaphragm mitochondria from septic mice: its relation with mitochondrial dysfunction and prevention by melatonin. Int J Biochem Cell Biol 2006; 38: 267-278.
370. Escames G, Lõpez LC, Ortiz F, et al. Attenuation of cardiac mitochondrial dysfunction by melatonin in septic mice. FEBS J 2007; 274: 2135-2147.
371. Ozen IO, Ekingen G, Taslipinar MY, et al. Effect of melatonin on healing of colonic anastomosis in a rat model of peritonitis. Eur Surg Res 2007; 39: 122-127.
372. Mayo JC, Sainz RM, Tan D-X, et al. Anti-inflammatory actions of melatonin and its metabolites, N1-acetyl-N2-formyl-5-methoxykynuramine (AFMK) and N1-acetyl-5-methoxykynuramine (AMK), in macrophages. J Neuroimmunol 2005; 165: 139-149.
373. Deng WG, Tang ST, Tseng HP, et al. Melatonin suppresses macrophage cyclooxygenase-2 and inducible nitric oxide synthase expression by inhibiting p52 acetylation and binding. Blood 2006; 108: 518-524.
374. Chen CF, Wang D, Reiter RJ, et al. Oral melatonin attenuates lung inflammation and airway hyperreactivity induced by inhalation of aerosolized pancreatic fluids in rats. J Pineal Res 2011; 50: 46-53.
375. Leõn J, Vives F, Crespo E, et al. Modification of nitric oxide synthase activity and neuronal response in rat striatum by melatonin and kynurenine derivatives. J Neuroendocrinol 1998; 10: 297-302.
376. Reiter RJ, Tan D-X, Burkhardt S,. Reactive oxygen and nitrogen species and cellular and organismal decline: amelioration with melatonin. Mech Ageing Dev 2002; 123: 1007-1019.
377. 1-acetyl-5- methoxykynuramine, a brain metabolite of melatonin. J Neurochem 2006; 98: 2023-2033.
378. Arese M, Magnifico MC, Mastronicola D, et al. Nanomolar melatonin enhances nNOS expression and controls HaCaT-cells bioenergetics. IUBMB Life 2012; 64: 251-258.
379. Sarti P, Magnifico MC, Altieri F, et al. New evidence for cross talk between melatonin and mitochondria mediated by a circadian-compatible interaction with nitric oxide. Int J Mol Sci 2013; 14: 11259-11276.
380. Hardeland R, Coto-Montes A, Poeggeler B,. Circadian rhythms, oxidative stress and antioxidative defense mechanisms. Chronobiol Int 2003; 20: 921-962.
381. Cristofanon S, Uguccioni F, Cerella C, et al. Intracellular prooxidant activity of melatonin induces a survival pathway involving NF-κB activation. Ann N Y Acad Sci 2009; 1171: 472-478.
382. Radogna F, Paternoster L, De Nicola M, et al. Rapid and transient stimulation of intracellular reactive oxygen species by melatonin in normal and tumor leukocytes. Toxicol Appl Pharmacol 2009; 239: 37-45.
383. + cells: a possible nuclear receptor-mediated mechanism involving T helper type 1 lymphocytes and monocytes. J Immunol 1997; 159: 574-581.
384. García-Mauriño S, González-Haba MG, Calvo JR, et al. Involvement of nuclear binding sites for melatonin in the regulation of IL-2 and IL-6 production by human blood mononuclear cells. J Neuroimmunol 1998; 92: 76-84.
385. Carrillo-Vico A, Lardone PJ, Fernandez-Santos JM, et al. Human lymphocyte-synthesized melatonin is involved in the regulation of the interleukin-2/interleukin-2 receptor system. J Clin Endocrinol Metab 2005; 90: 992-1000.
386. Lardone PJ, Carrillo-Vico A, Naranjo MC, et al. Melatonin synthesized by Jurkat human leukemic T cell line is implicated in IL-2 production. J Cell Physiol 2006; 206: 273-279.
387. Carrillo-Vico A, García-Mauriño S, Calvo JR, et al. Melatonin counteracts the inhibitory effect of PGE2 on IL-2 production in human lymphocytes via its mt1 membrane receptor. FASEB J 2003; 17: 755-757.
388. Kühlwein E, Irwin M,. Melatonin modulation of lymphocyte proliferation and Th1/Th2 cytokine expression. J Neuroimmunol 2001; 117: 51-57.
389. Raghavendra V, Singh V, Kulkarni SK, et al. Melatonin enhances Th2 cell mediated immune responses: lack of sensitivity to reversal by naltrexone or benzodiazepine receptor antagonists. Mol Cell Biochem 2001; 221: 57-62.
390. Carlberg C, Wiesenberg I,. The orphan receptor family RZR/ROR, melatonin and 5-lipoxygenase: an unexpected relationship. J Pineal Res 1995; 18: 171-178.
391. Steinhilber D, Brungs M, Werz O, et al. The nuclear receptor for melatonin represses 5-lipoxygenase gene expression in human B lymphocytes. J Biol Chem 1995; 270: 7037-7040.
392. Radogna F, Sestili P, Martinelli C, et al. Lipoxygenase-mediated pro-radical effect of melatonin via stimulation of arachidonic acid metabolism. Toxicol Appl Pharmacol 2009; 238: 170-177.
393. Radogna F, Diederich M, Ghibelli L,. Melatonin: a pleiotropic molecule regulating inflammation. Biochem Pharmacol 2010; 80: 1844-1852.
394. Davalos AR, Coppe JP, Campisi J, et al. Senescent cells as a source of inflammatory factors for tumor progression. Cancer Metastasis Rev 2010; 29: 273-283.
395. Acosta JC, Banito A, Wuestefeld T, et al. A complex secretory program orchestrated by the inflammasome controls paracrine senescence. Nat Cell Biol 2013; 15: 978-990.
396. Salminen A, Ojala J, Suuronen T, et al. Amyloid-beta oligomers set fire to inflammasomes and induce Alzheimer's pathology. J Cell Mol Med 2008; 12: 2255-2262.
397. Pizza V, Agresta A, D'Acunto CW, et al. Neuroinflammation and ageing: current theories and an overview of the data. Rev Recent Clin Trials 2011; 6: 189-203.
398. Maestroni GJM, Cardinali DP, Esquifino AI, et al. Does melatonin play a disease-promoting role in rheumatoid arthritis? J Neuroimmunol 2005; 158: 106-111.
399. Kireev RA, Tresguerres AC, Garcia C, et al. Melatonin is able to prevent the liver of old castrated female rats from oxidative and pro-inflammatory damage. J Pineal Res 2008; 45: 394-402.
400. Rai S, Haldar C, Singh R,. Modulation of immunity in young-adult and aged squirrel, Funambulus pennanti by melatonin and p-chlorophenylalanine. Immun Ageing 2009; 6: 5.
401. Ahmad R, Gupta S, Haldar C,. Age dependent expression of melatonin membrane receptor (MT1, MT2) and its role in regulation of nitrosative stress in tropical rodent Funambulus pennanti. Free Radic Res 2012; 46: 194-203.
402. Cuesta S, Kireev R, Forman K, et al. Melatonin improves inflammation processes in liver of senescence-accelerated prone male mice (SAMP8). Exp Gerontol 2010; 45: 950-956.
403. Cuesta S, Kireev R, García C, et al. Beneficial effect of melatonin treatment on inflammation, apoptosis and oxidative stress on pancreas of a senescence accelerated mice model. Mech Ageing Dev 2011; 132: 573-582.
404. Forman K, Vara E, García C, et al. Beneficial effects of melatonin on cardiological alterations in a murine model of accelerated aging. J Pineal Res 2010; 49: 312-320.
405. Forman K, Vara E, García C, et al. Effects of combined treatment with growth hormone and melatonin in the cardiological aging on male SAMP8 mice. J Gerontol A Biol Med Sci 2011; 66: 823.
406. Eşrefoǧlu M, Gül M, Ateş B, et al. The effects of caffeic acid phenethyl ester and melatonin on age-related vascular remodeling and cardiac damage. Fundam Clin Pharmacol 2011; 25: 580-590.
407. Kagawa Y,. From clock genes to telomeres in the regulation of the healthspan. Nutr Rev 2012; 70: 459-471.
408. Andrews NP, Fujii H, Goronzy JJ, et al. Telomeres and immunological diseases of aging. Gerontology 2010; 56: 390-403.
409. Tümpel S, Rudolph KL,. The role of telomere shortening in somatic stem cells and tissue aging: lessons from telomerase model systems. Ann N Y Acad Sci 2012; 1266: 28-39.
410. Wang FW, Wang Z, Zhang YM, et al. Protective effect of melatonin on bone marrow mesenchymal stem cells against hydrogen peroxide-induced apoptosis in vitro. J Cell Biochem 2013; 114: 2346-2355.
411. Yoo YM, Jung EM, Choi KC, et al. Effect of melatonin on mRNA expressions of transcription factors in murine embryonic stem cells. Brain Res 2011; 1385: 1-7.
412. Hardeland R, Poeggeler B,. Melatonin and synthetic melatonergic agonists: actions and metabolism in the central nervous system. Cent Nerv Syst Agents Med Chem 2012; 12: 189-216.
413. Ramírez-Rodríguez G, Klemoin F, Babu H, et al. Melatonin modulates cell survival of new neurons in the hippocampus of adult mice. Neuropsychopharmacology 2009; 34: 2180-2191.
414. Moriya T, Horie N, Mitome M, et al. Melatonin influences the proliferative and differentiative activity of neural stem cells. J Pineal Res 2007; 42: 411-418.
415. Chern CM, Liao JF, Wang YH, et al. Melatonin ameliorates neural function by promoting endogenous neurogenesis through the MT2 melatonin receptor in ischemic-stroke mice. Free Radic Biol Med 2012; 52: 1634-1647.
416. Fu J, Zhao SD, Liu HJ, et al. Melatonin promotes proliferation and differentiation of neural stem cells subjected to hypoxia in vitro. J Pineal Res 2011; 51: 104-112.
417. Sotthibundhu A, Phansuwan-Pujito P, Govitrapong P,. Melatonin increases proliferation of cultured neural stem cells obtained from adult mouse subventricular zone. J Pineal Res 2010; 49: 291-300.
418. Kong X, Li X, Cai Z, et al. Melatonin regulates the viability and differentiation of rat midbrain neural stem cells. Cell Mol Neurobiol 2008; 28: 569-579.
419. Tang Y, Cai B, Yuan F, et al. Melatonin pretreatment improves the survival and function of transplanted mesenchymal stem cells after focal cerebral ischemia. Cell Transplant 2013 [Epub ahead of print, Apr 29; doi: 10.3727/096368913x667510 ].
420. Stratos I, Richter N, Rotter R, et al. Melatonin restores muscle regeneration and enhances muscle function after crush injury in rats. J Pineal Res 2012; 52: 62-70.
421. Kannen V, Marini T, Zanette DL, et al. The melatonin action on stromal stem cells within pericryptal area in colon cancer model under constant light. Biochem Biophys Res Commun 2011; 405: 593-598.
422. Gao S, Wang ZL, Di KQ, et al. Melatonin imprives the reprogramming efficiency of murine-induced pluripotent stel cells using a secondary inducible system. J Pineal Res 2013; 55: 31-39.
423. 1/2 signaling cascade. J Pineal Res 2006; 40: 332-342.
424. Sanchez-Hidalgo M, Lu Z, Tan D-X, et al. Melatonin inhibits fatty acid-induced triglyceride accumulation in ROS17/2.8 cells: implications for osteoblast differentiation and osteoporosis. Am J Physiol Regul Integr Comp Physiol 2007; 292: R2208-R2215.
425. Amstrup AK, Sikjaer T, Mosekilde L, et al. Melatonin and the skeleton. Osteoporos Int 2013 [Epub ahead of print, May 29; doi: 10.1007/s00198-013-2404-8 ].
426. Liu X, Gong Y, Xiong K, et al. Melatonin mediates protective effects on inflammatory response induced by interleukin-1 beta on human mesenchymal stem cells. J Pineal Res 2013; 55: 14-25.
427. Zaminy A, Kashani IR, Barbarestani M, et al. Effects of melatonin on the proliferation and differentiation of rat adipose-derived stem cells. Indian J Plast Surg 2008; 41: 8-14.
428. Alvarez-García V, González A, Alonso-González C, et al. Melatonin interferes in the desmoplastic reaction in breast cancer by regulating cytokine production. J Pineal Res 2012; 52: 282-290.
429. Stehle JH, von Gall C, Korf HW,. Melatonin: a clock-output, a clock-input. J Neuroendocrinol 2003; 15: 383-389.
430. Skene DJ, Swaab DF,. Melatonin rhythmicity: effect of age and Alzheimer's disease. Exp Gerontol 2003; 38: 199-206.
431. Srinivasan V, Pandi-Perumal SR, Maestroni GJM, et al. Role of melatonin in neurodegenerative diseases. Neurotox Res 2005; 7: 293-318.
432. Wu YH, Fischer DF, Kalsbeek A, et al. Pineal clock gene oscillation is disturbed in Alzheimer's disease, due to functional disconnection from the "master clock". FASEB J 2006; 20: 1874-1876.
433. Wu YH, Swaab DF,. Disturbance and strategies for reactivation of the circadian rhythm system in aging and Alzheimer's disease. Sleep Med 2007; 8: 623-636.
434. Fu L, Pelicano H, Liu J, et al. The circadian gene Period2 plays an important role in tumor suppression and DNA damage response in vivo. Cell 2002; 111: 41-50.
435. Gery S, Gombart AF, Yi WS, et al. Transcription profiling of C/EBP targets identifies Per2 as a gene implicated in myeloid leukemia. Blood 2005; 106: 2827-2836.
436. Hua H, Wang Y, Wan C, et al. Inhibition of tumorigenesis by intratumoral delivery of the circadian gene mPer2 in C57BL/6 mice. Cancer Gene Ther 2007; 14: 815-818.
437. Chen-Goodspeed M, Lee CC,. Tumor suppression and circadian function. J Biol Rhythms 2007; 22: 291-298.
438. Min/+ tumorigenesis. Mol Cancer Res 2008; 6: 1786-1793.
439. Yang X, Wood PA, Ansell C, et al. Circadian time-dependent tumor suppressor function of period genes. Integr Cancer Ther 2009; 8: 309-316.
440. Sahar S, Sassone-Corsi P,. Metabolism and cancer: the circadian clock connection. Nat Rev Cancer 2009; 9: 886-896.
441. Lee S, Donehower LA, Herron AJ, et al. Disrupting circadian homeostasis of sympathetic signaling promotes tumor development in mice. PLoS ONE 2010; 5: e10995.
442. Scheiermann C, Kunisaki Y, Frenette PS,. Circadian control of the immune system. Nat Rev Immunol 2013; 13: 190-198.
443. Hashiramoto A, Yamane T, Tsumiyama K, et al. Mammalian clock gene Cryptochrome regulates arthritis via proinflammatory cytokine TNF-α. J Immunol 2010; 184: 1560-1565.
444. Yoshida K, Hashiramoto A, Okano T, et al. TNFα modulates expression of the circadian clock gene Per2 in rheumatoid synovial arthritis. Scand J Rheumatol 2013; 42: 276-280.
445. Rahman I, Kinnula VL, Gorbunova V, et al. SIRT1 as a therapeutic target in inflammaging of the pulmonary disease. Prev Med 2012; 54: S20-S28.
446. Yao H, Rahman I,. Perspectives in translational and therapeutic aspects of SIRT1 in inflammaging and senescence. Biochem Pharmacol 2012; 84: 1332-1339.
447. Yao H, Chung S, Hwang JW, et al. SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice. J Clin Invest 2012; 122: 2032-2045.
448. Swaab DF, Bao AM,. (Re-)activation of neurons in aging in dementia: lessons from the hypothalamus. Exp Gerontol 2011; 46: 178-184.
449. Asai M, Ikeda M, Akiyama M, et al. Administration of melatonin in drinking water promotes the phase advance of light-dark cycle in senescence-accelerated mice, SAMR1 but not SAMP8. Brain Res 2000; 876: 220-224.
450. Silver R, Schwartz WJ,. The suprachiasmatic nucleus is a functionally heterogeneous timekeeping organ. Methods Enzymol 2005; 393: 451-465.
451. Belle MD, Diekman CO, Forger DB, et al. Daily electrical silencing in the mammalian circadian clock. Science 2009; 326: 281-284.
452. Torres-Farfan C, Serõn-Ferré M, Dinet V, et al. Immunocytochemical demonstration of day/night changes of clock gene protein levels in the murine adrenal gland: differences between melatonin-proficient (C3H) and melatonin-deficient (C57BL) mice. J Pineal Res 2006; 40: 64-70.
453. Poeggeler B,. Melatonin, aging, and age-related diseases. Endocrine 2005; 27: 201-212.