Mediterranean diet and inflammaging within the hormesis paradigm

Nutrition Reviews

Volumn 75, Issue 6, 2017, Pages 442-455

  Martucci, Morena ^a   Ostan, Rita ^a   Biondi, Fiammetta ^a   Bellavista, Elena ^a   Fabbri, Cristina ^a   Bertarelli, Claudia ^a   Salvioli, Stefano ^a   Capri, Miriam ^a   Franceschi, Claudio ^b   Santoro, Aurelia ^a  

^a UNIVERSITY OF BOLOGNA   (Italy)

^b RIZZOLI ORTHOPAEDIC INSTITUTE   (Italy)

Author keywords

Hormesis; Inflammaging; Mediterranean diet; Nrf2; Stress

Indexed keywords

ALPHA TOCOPHEROL; ANTIOXIDANT; ASCORBIC ACID; CAFFEINE; CARBOHYDRATE; CARNOSIC ACID; CAROTENOID; EXTRA VIRGIN OLIVE OIL; FERULIC ACID; LIPID; LUTEOLIN; OLIVE OIL; OMEGA 3 FATTY ACID; PHENETHYL ISOTHIOCYANATE; PHYTOSTEROL; POLYPHENOL; PREBIOTIC AGENT; RESVERATROL; RETINOL; SULFUR; TERPENOID; TRANSCRIPTION FACTOR NRF2; NFE2L2 PROTEIN, HUMAN; PHYTOCHEMICAL; VITAMIN;

AGE; ANTIINFLAMMATORY ACTIVITY; ARTICLE; AUBERGINE; CALORIC RESTRICTION; CEREAL; CHRONIC STRESS; CONCEPTUAL FRAMEWORK; CULTURAL FACTOR; DIETARY FIBER; ETHNICITY; FISH; GARLIC; GRAPE; HEREDITY; HORMESIS; HUMAN; INFLAMMATION; LEAFY VEGETABLE; LEGUME; MEDITERRANEAN DIET; NONHUMAN; NUT; NUTRITION; ONION; RED WINE; SEX; TOMATO; VEGETABLE; WHOLE GRAIN; ADMINISTRATION AND DOSAGE; AGING; CARBOHYDRATE DIET; DIET THERAPY; GENETICS; HEALTHY LIFESTYLE; INTESTINE FLORA; OBSERVATIONAL STUDY; PHYSIOLOGICAL STRESS; PHYSIOLOGY; RANDOMIZED CONTROLLED TRIAL (TOPIC);

AGING; DIET, MEDITERRANEAN; DIETARY CARBOHYDRATES; DIETARY FIBER; GASTROINTESTINAL MICROBIOME; HEALTHY LIFESTYLE; HORMESIS; HUMANS; INFLAMMATION; NF-E2-RELATED FACTOR 2; OBSERVATIONAL STUDIES AS TOPIC; PHYTOCHEMICALS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; STRESS, PHYSIOLOGICAL; VITAMINS;

EID: 85020549511     PISSN: 00296643     EISSN: 17534887     Source Type: Journal    
DOI: 10.1093/nutrit/nux013     Document Type: Article

References (195)

1. Selye H. The Stress of Life. New York: McGraw-Hill Book Co; 1978.
2. Ottaviani E, Franceschi C. The neuroimmunology of stress from invertebrates to man. Prog Neurobiol. 1996;48:421-440.
3. Ottaviani E, Franchini A, Franceschi C. Pro-opiomelanocortin-derived peptides, cytokines, and nitric oxide in immune responses and stress: an evolutionary approach. Int Rev Cytol. 1997;170:79-141.
4. Ottaviani E, Franceschi C. A new theory on the common evolutionary origin of natural immunity, inflammation and stress response: the invertebrate phagocytic immunocyte as an eye-witness. Domest Anim Endocrinol. 1998;15:291-296.
5. Ottaviani E, Malagoli D, Capri M, et al. Ecoimmunology: is there any room for the neuroendocrine system? Bioessays. 2008;30:868-874.
6. Franceschi C, Bonafe M, Valensin S, et al. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann N Y Acad Sci. 2000;908:244-254.
7. Ostan R, Bucci L, Capri M, et al. Immunosenescence and immunogenetics of human longevity. Neuroimmunomodulation. 2008;15 :224-240.
8. Prenderville JA, Kennedy PJ, Dinan TG, et al. Adding fuel to the fire: the impact of stress on the ageing brain. Trends Neurosci. 2015;38:13-25.
9. Schulz H. Über Hefegifte. Pflugers Arch Ges Physiol Mensch Tiere. 1888;42:517-541.
10. Calabrese EJ, Baldwin LA. Defining hormesis. Hum Exp Toxicol. 2002;21:91-97.
11. Calabrese EJ, Bachmann KA, Bailer AJ, et al. Biological stress response terminology: integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework. Toxicol Appl Pharmacol. 2007;222:122-128.
12. Le Bourg E, Suresh R, eds. Mild Stress and Healthy Aging: Applying Hormesis in Aging Research and Intervention. Dordrecht, The Netherlands: Springer; 2008.
13. Calabrese EJ, Dhawan G, Kapoor R, et al. What is hormesis and its relevance to healthy aging and longevity? Biogerontology. 2015;16:693-707.
14. Rattan SI, Demirovic D. Hormesis can and does work in humans. Dose Response. 2009;8:58-63.
15. Demirovic D, Rattan SI. Establishing cellular stress response profiles as biomarkers of homeodynamics, health and hormesis. Exp Gerontol. 2013;48:94-98.
16. Franceschi C, Campisi J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J Gerontol A Biol Sci Med Sci. 2014;69(suppl 1):S4-S9.
17. Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell. 2014;159:709-713.
18. Spazzafumo L, Olivieri F, Abbatecola AM, et al. Remodelling of biological parameters during human aging: evidence for complex regulation in longevity and in type 2 diabetes. Age (Dordr). 2013;35:419-429.
19. Pall ML, Levine S. Nrf2, a master regulator of detoxification and also antioxidant, anti-inflammatory and other cytoprotective mechanisms, is raised by health promoting factors. Sheng Li Xue Bao. 2015;67:1-18.
20. Wakabayashi N, Itoh K, Wakabayashi J, et al. Keap1-null mutation leads to postnatal lethality due to constitutive Nrf2 activation. Nat Genet. 2003;35:238-245.
21. Rajasekaran NS, Connell P, Christians ES, et al. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Cell. 2007;130:427-439.
22. Maher J, Yamamoto M. The rise of antioxidant signaling-the evolution and hormetic actions of Nrf2. Toxicol Appl Pharmacol. 2010;244:4-15.
23. Rajasekaran NS, Varadharaj S, Khanderao GD, et al. Sustained activation of nuclear erythroid 2-related factor 2/antioxidant response element signaling promotes reductive stress in the human mutant protein aggregation cardiomyopathy in mice. Antioxid Redox Signal. 2011;14:957-971.
24. Tan NS, Wahli W. The emerging role of Nrf2 in dermatotoxicology. EMBO Mol Med. 2014;6:431-433.
25. Mattson MP, Cheng A. Neurohormetic phytochemicals: low dose toxins that induce adaptive neuronal stress responses. Trends Neurosci. 2006; 29:632-639.
26. Calabrese V, Cornelius C, Mancuso C, et al. Cellular stress response: a novel target for chemoprevention and nutritional neuroprotection in aging, neurodegenerative disorders and longevity. Neurochem Res. 2008;33:2444-2471.
27. Calabrese V, Butterfield DA, Giuffrida Stella AM. Aging and oxidative stress response in the CNS. In A Lajtha, P-PJ Regino, S Rossner, eds. Development and Aging Changes in the Nervous System. Handbook of Neurochemistry and Molecular Neurobiology, 3rd ed. New York: Springer; 2008:128-234.
28. Calabrese V, Cornelius C, Mancuso C, et al. Redox homeostasis and cellular stress response in aging and neurodegeneration. In: RM Uppu, SN Murthy, WA Pryor, et al., eds. Free Radical and Antioxidant Protocols, 2nd ed. Los Angeles: Humana Press; 2008.
29. Calabrese V, Cornelius C, Mancuso C, et al. Redox homeostasis and cellular stress response in aging and neurodegeneration. Methods Mol Biol. 2010;610:285-308.
30. Mancuso C, Bates TE, Butterfield DA, et al. Natural antioxidants in Alzheimer's disease. Expert Opin Investig Drugs. 2007;16:1921-1931.
31. Cornelius C, Perrotta R, Graziano A, et al. Stress responses, vitagenes and hormesis as critical determinants in aging and longevity: mitochondria as a "chi." Immun Ageing. 2013;10:15.
32. Hayes JD, Dinkova-Kostova AT. The Nrf2 regulatory network provides an interface between redox and intermediary metabolism. Trends Biochem Sci. 2014;39:199-218.
33. Kumar H, Kim IS, More SV, et al. Natural product-derived pharmacological modulators of Nrf2/ARE pathway for chronic diseases. Nat Prod Rep. 2014;31:109-139.
34. Landry J, Sutton A, Tafrov ST, et al. The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. Proc Natl Acad Sci U S A. 2000;97:5807-5811.
35. Michan S, Sinclair D. Sirtuins in mammals: insights into their biological function. Biochem J. 2007;404:1-13.
36. Dali-Youcef N, Lagouge M, Froelich S, et al. Sirtuins: the "magnificent seven," function, metabolism and longevity. Ann Med. 2007;39:335-345.
37. Calabrese V, Cornelius C, Dinkova-Kostova AT, et al. Vitagenes, cellular stress response, and acetylcarnitine: relevance to hormesis. Biofactors. 2009;35:146-160.
38. Villalba JM, Alcaín FJ. Sirtuin activators and inhibitors. Biofactors. 2012;38:349-359.
39. Calabrese EJ, Baldwin LA. Chemical hormesis: its historical foundations as a biological hypothesis. Toxicol Pathol. 1999;27:195-216.
40. Calabrese EJ, Baldwin LA. Hormesis: the dose-response revolution. Annu Rev Pharmacol Toxicol. 2003;43:175-197.
41. Calabrese EJ. Hormesis and medicine. Br J Clin Pharmacol. 2008;66:594-617.
42. Calabrese V, Pierluigi M, Cornelius C, et al. Phenolics in aging and neurodegenerative disorders. In: CG Fraga, ed. Phenolic Compounds of Plant Origin and Health: The Biochemistry Behind Their Nutritional and Pharmacological Value. New York: Wiley & Sons; 2009.
43. Calabrese V, Cornelius C, Mancuso C, et al. Vitagenes, dietary antioxidants and neuroprotection in neurodegenerative diseases. Front Biosci (Landmark Ed). 2009;14:376-397.
44. Bellia F, Calabrese V, Guarino F, et al. Carnosinase levels in aging brain: redox state induction and cellular stress response. Antioxid Redox Signal. 2009;11:2759-2775.
45. Calabrese V, Cornelius C, Trovato A, et al. The hormetic role of dietary antioxidants in free radical-related diseases. Curr Pharm Des. 2010;16:877-883.
46. Liu J, Head E, Gharib AM, et al. Memory loss in old rats is associated with brain mitochondrial decay and RNA/DNA oxidation: partial reversal by feeding acetyl- L-carnitine and/or R-alpha -lipoic acid. Proc Natl Acad Sci U S A. 2002;99:2356-2361.
47. Calabrese V, Guagliano E, Sapienza M, et al. Redox regulation of cellular stress response in aging and neurodegenerative disorders: role of vitagenes. Neurochem Res. 2007;32:757-773.
48. Mattson MP, Son TG, Camandola S. Viewpoint: mechanisms of action and therapeutic potential of neurohormetic phytochemicals. Dose Response. 2007;5:174-186.
49. Son TG, Camandola S, Mattson MP. Hormetic dietary phytochemicals. Neuromolecular Med. 2008;10:236-246.
50. Mattson MP. Dietary factors, hormesis and health. Ageing Res Rev. 2008;7:43-48.
51. Calabrese EJ, Blain R. The occurrence of hormetic dose responses in the toxicological literature, the hormesis database: an overview. Toxicol Appl Pharmacol. 2005;202:289-301.
52. Rattan SI. Hormesis in aging. Ageing Res Rev. 2008;7:63-78.
53. Calabrese EJ, Dhawan G, Kapoor R, et al. What is hormesis and its relevance to healthy aging and longevity? Biogerontology. 2015;16:693-707.
54. Grayson BE, Hakala-Finch AP, Kekulawala M, et al. Weight loss by calorie restriction versus bariatric surgery differentially regulates the hypothalamo-pituitaryadrenocortical axis in male rats. Stress. 2014;17:484-493.
55. Pijl H. Longevity. The allostatic load of dietary restriction. Physiol Behav. 2012;106:51-57.
56. Mockett RJ, Cooper TM, Orr WC, et al. Effects of caloric restriction are speciesspecific. Biogerontology. 2006;7:157-160.
57. Liao CY, Rikke BA, Johnson TE, et al. Genetic variation in the murine lifespan response to dietary restriction: from life extension to life shortening. Aging Cell. 2010;9:92-95.
58. Keys A, Menotti A, Aravanis C, et al. The seven countries study: 2,289 deaths in 15 years. Prev Med. 1984;13:141-154.
59. Korre M, Tsoukas MA, Frantzeskou E, et al. Mediterranean diet and workplace health promotion. Curr Cardiovasc Risk Rep. 2014;8:416.
60. Intergovernmental Committee for the Safeguarding of the Intangible Cultural Heritage. Decision of the Intergovernmental Committee: 8.COM 8.10. Published 2013. http://www.unesco.org/culture/ich/en/decisions/8.COM/8.10. Accessed June 15, 2016.
61. Bach-Faig A, Berry EM, Lairon D, et al. Mediterranean Diet Foundation Expert Group. Mediterranean diet pyramid today. Science and cultural updates. Public Health Nutr. 2011;14:2274-2284.
62. Calabrese V, Cornelius C, Dinkova-Kostova AT, et al. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal. 2010;13:1763-1811.
63. Lee J, Jo DG, Park D, et al. Adaptive cellular stress pathways as therapeutic targets of dietary phytochemicals: focus on the nervous system. Pharmacol Rev. 2014;66:815-868.
64. Zhao B. Natural antioxidants protect neurons in Alzheimer's disease and Parkinson's disease. Neurochem Res. 2009;34:630-638.
65. Calabrese EJ. Alzheimer's disease drugs: an application of the hormetic doseresponse model. Crit Rev Toxicol. 2008;38:419-451.
66. Srinivasan M, Sudheer AR, Menon VP. Ferulic acid: therapeutic potential through its antioxidant property. J Clin Biochem Nutr. 2007;40:92-100.
67. Ou L, Kong LY, Zhang XM, et al. Oxidation of ferulic acid by Momordica charantia peroxidase and related anti-inflammation activity changes. Biol Pharm Bull. 2003;26:1511-1516.
68. Tetsuka T, Baier LD, Morrison AR. Antioxidants inhibit interleukin-1-induced cyclooxygenase and nitric-oxide synthase expression in rat mesangial cells. Evidence for post-transcriptional regulation. J Biol Chem. 1996;271:11689-11693.
69. Murakami A, Nakamura Y, Koshimizu K, et al. FA15, a hydrophobic derivative of ferulic acid, suppresses inflammatory responses and skin tumor promotion: comparison with ferulic acid. Cancer Lett. 2002;180:121-129.
70. Kawabata K, Yamamoto T, Hara A, et al. Modifying effects of ferulic acid on azoxymethane-induced colon carcinogenesis in F344 rats. Cancer Lett. 2000;157:15-21.
71. Asanoma M, Takahashi K, Miyabe M, et al. Inhibitory effect of topical application of polymerized ferulic acid, a synthetic lignin, on tumor promotion in mouse skin two-stage tumorigenesis. Carcinogenesis. 1994;15:2069-2071.
72. Kim HS, Cho JY, Kim DH, et al. Inhibitory effects of long-term administration of ferulic acid on microglial activation induced by intracerebroventricular injection of beta-amyloid peptide (1-42) in mice. Biol Pharm Bull. 2004;27:120-121.
73. Nakamura Y, Torikai K, Ohto Y, et al. A simple phenolic antioxidant protocatechuic acid enhances tumor promotion and oxidative stress in female ICR mouse skin: dose-and timing-dependent enhancement and involvement of bioactivation by tyrosinase. Carcinogenesis. 2000;21:1899-1907.
74. Murakami A, Kadota M, Takahashi D, et al. Suppressive effects of novel ferulic acid derivatives on cellular responses induced by phorbol ester, and by combined lipopolysaccharide and interferon-gamma. Cancer Lett. 2000;157:77-85.
75. Ueda H, Yamazaki C, Yamazaki M. Inhibitory effect of Perilla leaf extract and luteolin on mouse skin tumor promotion. Biol Pharm Bull. 2003;26:560-563.
76. Huang YT, Hwang JJ, Lee PP, et al. Effects of luteolin and quercetin, inhibitors of tyrosine kinase, on cell growth and metastasis-associated properties in A431 cells overexpressing epidermal growth factor receptor. Br J Pharmacol. 1999;128:999-1010.
77. Ko WG, Kang TH, Lee SJ, et al. Effects of luteolin on the inhibition of proliferation and induction of apoptosis in human myeloid leukaemia cells. Phytother Res. 2002;16:295-298.
78. Dajas F, Rivera F, Blasina F, et al. Cell culture protection and in vivo neuroprotective capacity of flavonoids. Neurotox Res. 2003;5:425-432.
79. Wruck CJ, Claussen M, Fuhrmann G, et al. Luteolin protects rat PC12 and C6 cells against MPP+ induced toxicity via an ERK dependent Keap1-Nrf2-ARE pathway. J Neural Transm Suppl. 2007;72:57-67.
80. Tookey HL, VanEtten CH, Daxenbichler ME. Glucosinolates. In: IE Liener, ed. Toxic Constituents of Plant Staffs. New York: Academic Press; 1980:103-142.
81. Carlson DG, Daxenbichler ME, VanEtten CH, et al. Glucosinolates in crucifer vegetables: turnips and rutabagas. J Agric Food Chem. 1981;29:1235-1239.
82. Wattenberg LW. Inhibition of carcinogenic effects of polycyclic hydrocarbons by benzyl isothiocyanate and related compounds. J Natl Cancer Inst. 1977;58:395-398.
83. Morse MA, Eklind KI, Amin SG, et al. Effects of alkyl chain length on the inhibition of NNK-induced lung neoplasia in A/J mice by arylalkyl isothiocyanates. Carcinogenesis. 1989;10:1757-1759.
84. Morse MA, Wang CX, Stoner GD, et al. Inhibition of 4-(methylnitrosamino)-1-(3-pyridyl)- 1-butanone-induced DNA adduct formation and tumorigenicity in the lung of F344 rats by dietary phenethyl isothiocyanate. Cancer Res. 1989;49:549-553.
85. Su JC, Lin K, Wang Y, et al. In vitro studies of phenethyl isothiocyanate against the growth of LN229 human glioma cells. Int J Clin Exp Pathol. 2015;8:4269-4276.
86. Yeh YT, Yeh H, Su SH, et al. Phenethyl isothiocyanate induces DNA damageassociated G2/M arrest and subsequent apoptosis in oral cancer cells with varying p53 mutations. Free Radic Biol Med. 2014;74:1-13.
87. Pawlik A, Szczepanski MA, Klimaszewska A, et al. Phenethyl isothiocyanateinduced cytoskeletal changes and cell death in lung cancer cells. Food Chem Toxicol. 2012;50:3577-3594.
88. Hecht SS. Inhibition of carcinogenesis by isothiocyanates. Drug Metab Rev. 2000;32:395-411.
89. Conaway CC, Yang YM, Chung FL. Isothiocyanates as cancer chemopreventive agents: their biological activities and metabolism in rodents and humans. Curr Drug Metab. 2002;3:233-255.
90. Kleszczyński K, Ernst IM, Wagner AE, et al. Sulforaphane and phenylethyl isothiocyanate protect human skin against UVR-induced oxidative stress and apoptosis: role of Nrf2-dependent gene expression and antioxidant enzymes. Pharmacol Res. 2013;78:28-40.
91. Harikumar KB, Aggarwal BB. Resveratrol: a multitargeted agent for ageassociated chronic diseases. Cell Cycle. 2008;7:1020-1035.
92. Mukherjee S, Dudley JI, Das DK. Dose-dependency of resveratrol in providing health benefits. Dose Response. 2010;8:478-500.
93. Goldberg, DM, Yan J, Soleas GJ. Absorption of three wine-related polyphenols in three different matrices by healthy subjects. Clin Biochem. 2003;36:79-87.
94. Pazoki-Toroudi H, Amani H, Ajami M, et al. Targeting mTOR signaling by polyphenols: a new therapeutic target for ageing. Ageing Res Rev. 2016;31:55-66.
95. Calabrese EJ, Mattson MP, Calabrese V. Dose response biology: the case of resveratrol. Hum Exp Toxicol. 2010;29:1034-1037.
96. Mark PM, Aiwu C. Neurohormetic phytochemicals: low-dose toxins that induce adaptive neuronal stress responses. Trends Neurosci. 2006;29:632-639.
97. Wood JG, Rogina B, Lavu S, et al. Sirtuin activators mimic caloric restriction and delay ageing in metazoans. Nature. 2004;430:686-689.
98. Bonkowski MS, Sinclair DA. Slowing ageing by design: the rise of NAD(+) and sirtuin-activating compounds. Nat Rev Mol Cell Biol. 2016;17:679-690.
99. Testa G, Biasi F, Poli G, et al. Calorie restriction and dietary restriction mimetics: a strategy for improving healthy aging and longevity. Curr Pharm Des. 2014;20:2950-2977.
100. Jang JH, Surh YJ. Protective effect of resveratrol on beta-amyloid-induced oxidative PC12 cell death. Free Radic Biol Med. 2003;34:1100-1110.
101. Capiralla H, Vingtdeux V, Zhao H, et al. Resveratrol mitigates lipopolysaccharideand Ab-mediated microglial inflammation by inhibiting the TLR4/NF-jB/STAT signaling cascade. J Neurochem. 2012;120:461-472.
102. Zhong LM, Zong Y, Sun L, et al. Resveratrol inhibits inflammatory responses via the mammalian target of rapamycin signaling pathway in cultured LPSstimulated microglial cells. PLoS One. 2012;7:e32195.
103. Corbi G, Conti V, Davinelli S, et al. Dietary phytochemicals in neuroimmunoaging: a new therapeutic possibility for humans? Front Pharmacol. 2016;7:364.
104. Conti V, Izzo V, Corbi G, et al. Antioxidant supplementation in the treatment of aging-associated diseases. Front Pharmacol. 2016;7:24.
105. Liu K, Zhou R, Wang B, et al. Effect of resveratrol on glucose control and insulin sensitivity: a meta-analysis of 11 randomized controlled trials. Am J Clin Nutr. 2014;99:1510-1519.
106. Timmers S, de Ligt M, Phielix E, et al. Resveratrol as add-on therapy in subjects with well-controlled type 2 diabetes: a randomized controlled trial. Diabetes Care. 2016;39:2211-2217.
107. Lee J, Torosyan N, Silverman DH. Examining the impact of grape consumption on brain metabolism and cognitive function in patients with mild decline in cognition: a double-blinded placebo controlled pilot study. Exp Gerontol. 2017(Pt2):121-128.
108. Suresh R, Le Bourg E, eds. Hormesis in Health and Disease. Boca Raton, FL: CRC Press; 2014.
109. Kafatos A, Verhagen H, Moschandreas J, et al. Mediterranean diet of Crete: foods and nutrient content. J Am Diet Assoc. 2000;100:1487-1493.
110. Simopoulos AP. The Mediterranean diets: what is so special about the diet of Greece? The scientific evidence. J Nutr. 2001;131(suppl 11):3065S-3073S.
111. Willcox DC, Willcox BJ, Todoriki H, et al. The Okinawan diet: health implications of a low-calorie, nutrient-dense, antioxidant-rich dietary pattern low in glycemic load. J Am Coll Nutr. 2009;28(suppl):500S-516S.
112. Cipollina C, Salvatore SR, Muldoon MF, et al. Generation and dietary modulation of anti-inflammatory electrophilic omega-3 fatty acid derivatives. PLoS One. 2014;9:e94836.
113. Willett WC, Sacks F, Trichopoulou A, et al. Mediterranean diet pyramid: a cultural model for healthy eating. Am J Clin Nutr. 1995;61(suppl 6):1402S-1406S.
114. Salvioli S, Sikora E, Cooper EL, et al. Curcumin in cell death processes: a challenge for CAM of age-related pathologies. Evid Based Complement Alternat Med. 2007;4:181-190.
115. Bellavista E, Andreoli F, Parenti MD, et al. Immunoproteasome in cancer and neuropathologies: a new therapeutic target? Curr Pharm Des. 2013;19:702-718.
116. Chondrogianni N, Voutetakis K, Kapetanou M, et al. Proteasome activation: an innovative promising approach for delaying aging and retarding age-related diseases. Ageing Res Rev. 2015;23(pt A):37-55.
117. Chondrogianni N, Chinou I, Rivett AJ, et al. The olive constituent oleuropein exhibits proteasome stimulatory properties in vitro and confers life span extension of human embryonic fibroblasts. Rejuvenation Res. 2007;10:157-172.
118. Chondrogianni N, Kapeta S, Chinou I, et al. Anti-ageing and rejuvenating effects of quercetin. Exp Gerontol. 2010;45:763-771.
119. Höhn TJ, Grune T. The proteasome and the degradation of oxidized proteins: part III-redox regulation of the proteasomal system. Redox Biol. 2014;2:388-394.
120. Eaton DL, Klaassen CD. Principles of toxicology. In: CD Klassen, ed. Casarett and Doull's Toxicology. The Basic Science of Poisons. 6th ed. New York, McGraw-Hill; 2001:11-34.
121. Hayes DP. Nutritional hormesis. Eur J Clin Nutr. 2007;61:147-159.
122. Kodentsova VM, Vrzhesinskaia OA, Mazo VK. Vitamins and oxidative stress. Vopr Pitan. 2013;82:11-18.
123. Álvarez R, Vaz B, Gronemeyer H, et al. Functions, therapeutic applications, and synthesis of retinoids and carotenoids. Chem Rev. 2014;114:1-125.
124. Amir AB, Ghobadi S. Studies on oxidants and antioxidants with a brief glance at their relevance to the immune system. Life Sci. 2016;146:163-173.
125. Traber MG, Stevens JF. Vitamins C and E: Beneficial effects from a mechanistic perspective. Free Radic Biol Med. 2011;51:1000-1013.
126. Wu D, Meydani SN. Age-associated changes in immune function: impact of vitamin E intervention and the underlying mechanisms. Endocr Metab Immune Disord Drug Targets. 2014;14:283-289.
127. Chauhan SS, Celi P, Fahri FT, et al. Dietary antioxidants at supranutritional doses modulate skeletal muscle heat shock protein and inflammatory gene expression in sheep exposed to heat stress. J Anim Sci. 2014;92:4897-4908.
128. Bierhaus A, Wolf J, Andrassy M, et al. A mechanism converting psychosocial stress into mononuclear cell activation. Proc Natl Acad Sci U S A. 2003;100:1920-1925.
129. Elisia I, Kitts DD. Tocopherol isoforms (a-, c-, and d-) show distinct capacities to control Nrf-2 and NfjB signaling pathways that modulate inflammatory response in Caco-2 intestinal cells. Mol Cell Biochem. 2015;404:123-131.
130. De Lorgeril M, Salen P. New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids. BMC Med. 2012;10:50.
131. Ferraz AC, Delattre AM, Almendra RG, et al. Chronic omega- 3 fatty acids supplementation promotes beneficial effects on anxiety, cognitive and depressive-like behaviors in rats subjected to a restraint stress protocol. Behav Brain Res 2011;219:116-122.
132. Parker G, Gibson NA, Brotchie H, et al. Omega-3 fatty acids and mood disorders. Am J Psychiatry. 2006;163:969-978.
133. Martins JG. EPA but not DHA appears to be responsible for the efficacy of omega-3 long chain polyunsaturated fatty acid supplementation in depression: evidence from a meta-analysis of randomized controlled trials. J Am Coll Nutr. 2009;28:525-542.
134. Giles GE, Mahoney CR, Kanarek RB. Omega-3 fatty acids influence mood in healthy and depressed individuals. Nutr Rev. 2013;71:727-741.
135. Delarue J, Matzinger O, Binnert C, et al. Fish oil prevents the adrenal activation elicited by mental stress in healthy men. Diabetes Metab. 2003;29:289-295.
136. Lin PY, Huang SY, Su KP. A meta-analytic review of polyunsaturated fatty acid compositions in patients with depression. Biol Psychiatry. 2010;68:140-147.
137. Jolly CA, Muthukumar A, Avula CP, et al. Life span is prolonged in food-restricted autoimmune-prone (NZB×NZW)F(1) mice fed a diet enriched with (n-3) fatty acids. J Nutr. 2001;131:2753-2760.
138. Zhao Y, Joshi-Barve S, Barve S, et al. Eicosapentaenoic acid prevents LPS-induced TNF-alpha expression by preventing NF-kappaB activation. J Am Coll Nutr. 2004;23:71-78.
139. Wall R, Ross RP, Fitzgerald GF, et al. Fatty acids from fish: the anti-inflammatory potential of long-chain omega-3 fatty acids. Nutr Rev. 2010;68:280-289.
140. Saw CL, Yang AY, Guo Y, et al. Astaxanthin and omega-3 fatty acids individually and in combination protect against oxidative stress via the Nrf2-ARE pathway. Food Chem Toxicol. 2013;62:869-875.
141. Aparicio-Soto M, Sánchez-Hidalgo M, Rosillo MÁ, et al. Extra virgin olive oil: a key functional food for prevention of immune-inflammatory diseases. Food Funct. 2016;7:4492-4505.
142. Estruch R, Ros E, Salas-Salvado J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279-1290.
143. Turner R, Etienne N, Alonso MG, et al. Antioxidant and anti-atherogenic activities of olive oil phenolics. Int J Vitam Nutr Res. 2005;75:61-70.
144. Piroddi M, Albini A, Fabiani R, et al. Nutrigenomics of extra-virgin olive oil: a review. Biofactors. 2017;43:17-41.
145. Galli F, Azzi A, Birringer M, et al. Vitamin E: emerging aspects and new directions. Free Radic Biol Med. 2016;102:16-36.
146. Ghanbari R, Anwar F, Alkharfy KM, et al. Valuable nutrients and functional bioactives in different parts of olive (Olea europaea L.)-a review. Int J Mol Sci. 2012;13:3291-3340.
147. Tsimidou MZ. Virgin olive oil (VOO) and other olive tree products as sources of atocopherol. Updating and perspective. In: A Catala, ed. Tocopherol: Sources, Uses and Health Benefits. New York: Nova Science Publisher; 2012:1-21.
148. Galli F. Interactions of polyphenolic compounds with drug disposition and metabolism. Curr Drug Metab. 2007;8:830-838.
149. Forman HJ, Davies KJ, Ursini F. How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radic Biol Med. 2014;66:24-35.
150. Martin MA, Ramos S, Granado-Serrano AB, et al. Hydroxytyrosol induces antioxidant/ detoxificant enzymes and Nrf2 translocation via extracellular regulated kinases and phosphatidylinositol-3-kinase/protein kinase B pathways in HepG2 cells. Mol Nutr Food Res. 2010;54:956-966.
151. Zou X, Feng Z, Li Y, et al. Stimulation of GSH synthesis to prevent oxidative stress-induced apoptosis by hydroxytyrosol in human retinal pigment epithelial cells: activation of Nrf2 and JNK-p62/SQSTM1 pathways. J Nutr Biochem. 2012;23:994-1006.
152. Parzonko A, Czerwinska ME, Kiss AK, et al. Oleuropein and oleacein may restore biological functions of endothelial progenitor cells impaired by angiotensin II via activation of Nrf2/heme oxygenase-1 pathway. Phytomedicine. 2013;20:1088-1094.
153. Bayram B, Ozcelik B, Grimm S, et al. A diet rich in olive oil phenolics reduces oxidative stress in the heart of SAMP8 mice by induction of Nrf2-dependent gene expression. Rejuvenation Res. 2012;15:71-81.
154. Menendez JA, Joven J, Aragone`s G, et al. Xenohormetic and anti-aging activity of secoiridoid polyphenols present in extra virgin olive oil: a new family of gerosuppressant agents. Cell Cycle. 2013;12:555-578.
155. Zhang B, Kang M, Xie Q, et al. Anthocyanins from Chinese bayberry extract protect b cells from oxidative stress-mediated injury via HO-1 upregulation. J Agric Food Chem. 2011;59:537-545.
156. Mirrahimi A, Chiavaroli L, Srichaikul K, et al. The role of glycemic index and glycemic load in cardiovascular disease and its risk factors: a review of the recent literature. Curr Atheroscler Rep. 2014;16:381.
157. Kalogeropoulos N, Chiou A, Ioannou M, et al. Nutritional evaluation and bioactive microconstituents (phytosterols, tocopherols, polyphenols, triterpenic acids) in cooked dry legumes usually consumed in the Mediterranean countries. Chemistry. 2010;121:682-690.
158. Lee JH, Gao J, Kosinski PA, et al. Heat shock protein 90 (HSP90) inhibitors activate the heat shock factor 1 (HSF1) stress response pathway and improve glucose regulation in diabetic mice. Biochem Biophys Res Commun. 2013;430:1109-1113.
159. Kurucz I, Morva A, Vaag A, et al. Decreased expression of heat shock protein 72 in skeletal muscle of patients with type 2 diabetes correlates with insulin resistance. Diabetes. 2002;51:1102-1109.
160. Ma Y, Griffith JA, Chasan-Taber L, et al. Association between dietary fiber and serum C-reactive protein. Am J Clin Nutr. 2006;83:760-766.
161. Ma Y, Hébert JR, Li W, et al. Association between dietary fiber and markers of systemic inflammation in the Women's Health Initiative Observational Study. Nutrition. 2008;24:941-949.
162. Chuang SC, Vermeulen R, Sharabiani MT, et al. The intake of grain fibers modulates cytokine levels in blood. Biomarkers. 2011;16:504-510.
163. Reddy BS, Hirose Y, Cohen LA, et al. Preventive potential of wheat bran fractions against experimental colon carcinogenesis: implications for human colon cancer prevention. Cancer Res. 2000;60:4792-4797.
164. Costa GT, Abreu GC, Guimarães AB, et al. Fructo-oligosaccharide effects on serum cholesterol levels. An overview. Acta Cir Bras. 2015;30:366-370.
165. Candela M, Turroni S, Garagnani P, et al. Ageing and gut microbes: perspectives for health maintenance and longevity. Pharmacol Res. 2013;69:11-20.
166. Joseph JA, Shukitt-Hale B, Casadesus G. Reversing the deleterious effects of aging on neuronal communication and behavior: beneficial properties of fruit polyphenolic compounds. Am J Clin Nutr. 2005;81(suppl 1):313S-316S.
167. Huang PL. Nitric oxide and cerebral ischemic preconditioning. Cell Calcium. 2004;36:323-329.
168. Doré S, Goto S, Sampei K, et al. Heme oxygenase-2 acts to prevent neuronal death in brain cultures and following transient cerebral ischemia. Neuroscience. 2000;99:587-592.
169. Jiang X, Tian F, Mearow K, et al. The excitoprotective effect of N-methyl-D-aspartate receptors is mediated by a brain-derived neurotrophic factor autocrine loop in cultured hippocampal neurons. J Neurochem. 2005;94:713-722.
170. Sée V, Boutillier AL, Bito H, et al. Calcium/calmodulin-dependent protein kinase type IV (CaMKIV) inhibits apoptosis induced by potassium deprivation in cerebellar granule neurons. FASEB J. 2001;15:134-144.
171. Chen C, Pung D, Leong V, et al. Induction of detoxifying enzymes by garlic organosulfur compounds through transcription factor Nrf2: effect of chemical structure and stress signals. Free Radic Biol Med. 2004;37:1578-1590.
172. Sun MM, Bu H, Li B, et al. Neuroprotective potential of phase II enzyme inducer diallyl trisulfide. Neurol Res. 2009;31:23-27.
173. Kosaka K, Yokoi T. Carnosic acid, a component of rosemary (Rosmarinus officinalis L.), promotes synthesis of nerve growth factor in T98G human glioblastoma cells. Biol Pharm Bull. 2003;26:1620-1622.
174. Satoh T, Kosaka K, Itoh K, et al. Carnosic acid, a catechol-type electrophilic compound, protects neurons both in vitro and in vivo through activation of the Keap1/Nrf2 pathway via S-alkylation of targeted cysteines on Keap1. J Neurochem. 2008;104:1116-1131.
175. Mimura J, Kosaka K, Maruyama A, et al. Nrf2 regulates NGF mRNA induction by carnosic acid in T98G glioblastoma cells and normal human astrocytes. J Biochem. 2011;150:209-217.
176. Tamaki Y, Tabuchi T, Takahashi T, et al. Activated glutathione metabolism participates in protective effects of carnosic acid against oxidative stress in neuronal HT22 cells. Planta Med. 2010;76:683-688.
177. Kosaka K, Mimura J, Itoh K, et al. Role of Nrf2 and p62/ZIP in the neurite outgrowth by carnosic acid in PC12h cells. J Biochem. 2010;147:73-81.
178. Sonsalla PK, Wong LY, Harris SL, et al. Delayed caffeine treatment prevents nigral dopamine neuron loss in a progressive rat model of Parkinson's disease. Exp Neurol. 2012;234:482-487.
179. Sallaberry C, Nunes F, Costa MS, et al. Chronic caffeine prevents changes in inhibitory avoidance memory and hippocampal BDNF immunocontent in middleaged rats. Neuropharmacology. 2013;64:153-159.
180. Laurent C, Eddarkaoui S, Derisbourg M, et al. Beneficial effects of caffeine in a transgenic model of Alzheimer's disease-like tau pathology. Neurobiol Aging. 2014;35:2079-2090.
181. Scapagnini G, Butterfield DA, Colombrita C, et al. Ethyl ferulate, a lipophilic polyphenol, induces HO-1 and protects rat neurons against oxidative stress. Antioxid Redox Signal. 2004;6:811-818.
182. Perluigi M, Joshi G, Sultana R, et al. In vivo protective effects of ferulic acid ethyl ester against amyloid-beta peptide 1-42-induced oxidative stress. J Neurosci Res. 2006;84:418-426.
183. Caracciolo B, Xu W, Collins S, et al. Cognitive decline, dietary factors and gutbrain interactions. Mech Ageing Dev. 2014;136-137:59-69.
184. Petra AI, Panagiotidou S, Hatziagelaki E, et al. Gut-microbiota-brain axis and its effect on neuropsychiatric disorders with suspected immune dysregulation. Clin Ther. 2015;37:984-995.
185. Berer K, Mues M, Koutrolos M, et al. Commensal microbiota and myelin autoantigen cooperate to trigger autoimmune demyelination. Nature. 2011;479:538-541.
186. Hornig M. The role of microbes and autoimmunity in the pathogenesis of neuropsychiatric illness. Curr Opin Rheumatol. 2013;25:488-795.
187. Sheedy JR, Wettenhall RE, Scanlon D, et al. Increased d-lactic Acid intestinal bacteria in patients with chronic fatigue syndrome. In Vivo. 2009;23:621-628.
188. Skowrońska M, Albrecht J. Alterations of blood brain barrier function in hyperammonemia: an overview. Neurotox Res. 2012;21:236-244.
189. Qureshi MO, Khokhar N, Shafqat F. Ammonia levels and the severity of hepatic encephalopathy. J Coll Physicians Surg Pak. 2014;24:160-163.
190. NU-AGE Consortium. European Project NU-AGE. http://www.nu-age.eu. Accessed January 10, 2017.
191. Santoro A, Pini E, Scurti M, et al. NU-AGE Consortium. Combating inflammaging through a Mediterranean whole diet approach: the NU-AGE project's conceptual framework and design. Mech Ageing Dev. 2014;136-137:3-13.
192. Berendsen A, Santoro A, Pini E, et al. Reprint of: a parallel randomized trial on the effect of a healthful diet on inflammageing and its consequences in European elderly people: design of the NU-AGE dietary intervention study. Mech Ageing Dev. 2014;136-137:14-21.
193. Santoro A, Brigidi P, Gonos ES, et al. (Eds.) Mediterranean diet and inflammaging in the elderly: the European project NU-AGE. Mech Ageing Dev. 2014;136-137 (Special Issue):1-162.
194. Franceschi C, Garagnani P, Vitale G, et al. Inflammaging and "garb-aging." Trends Endocrinol Metab. 2017;28:199-212.
195. Gems D, Partridge L. Stress-response hormesis and aging: "that which does not kill us makes us stronger." Cell Metab. 2008;7:200-203.