Olive oil and the hallmarks of aging

Molecules

Volumn 21, Issue 2, 2016, Pages

  Del Río, Lucía Fernández ^a   Gutiérrez Casado, Elena ^a   Varela López, Alfonso ^b   Villalba, José M ^a  

^a UNIVERSITY OF CÓRDOBA   (Spain)

^b UNIVERSITY OF GRANADA   (Spain)

Author keywords

DNA damage; Fatty acids; Hallmarks of aging; Mediterranean diet; Olive oil; Oxidative stress; Polyphenols; Senescence

Indexed keywords

EDIBLE OIL; OLIVE OIL;

AGING; ANIMAL; CELL AGING; CELL COMMUNICATION; DRUG EFFECTS; GENETIC EPIGENESIS; GENETICS; HUMAN;

AGING; ANIMALS; CELL AGING; CELL COMMUNICATION; DIETARY FATS, UNSATURATED; EPIGENESIS, GENETIC; HUMANS; OLIVE OIL;

EID: 84963685659     PISSN: None     EISSN: 14203049     Source Type: Journal    
DOI: 10.3390/molecules21020163     Document Type: Review

References (218)

1. Lopez-Otin, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The hallmarks of aging. Cell 2013, 153, 1194-1217. [CrossRef]
2. Li, M.; Izpisua Belmonte, J.C. Ageing: Genetic rejuvenation of old muscle. Nature 2014, 506, 304-305. [CrossRef] [PubMed]
3. Sousa-Victor, P.; Gutarra, S.; Garcia-Prat, L.; Rodriguez-Ubreva, J.; Ortet, L.; Ruiz-Bonilla, V.; Jardi, M.; Ballestar, E.; Gonzalez, S.; Serrano, A.L.; et al. Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 2014, 506, 316-321. [CrossRef] [PubMed]
4. Mitsui, A.; Hamuro, J.; Nakamura, H.; Kondo, N.; Hirabayashi, Y.; Ishizaki-Koizumi, S.; Hirakawa, T.; Inoue, T.; Yodoi, J. Overexpression of human thioredoxin in transgenic mice controls oxidative stress and life span. Antioxid. Redox Signal. 2002, 4, 693-696. [CrossRef] [PubMed]
5. Schriner, S.E.; Linford, N.J.; Martin, G.M.; Treuting, P.; Ogburn, C.E.; Emond, M.; Coskun, P.E.; Ladiges, W.; Wolf, N.; Van Remmen, H.; et al. Extension of murine life span by overexpression of catalase targeted to mitochondria. Science 2005, 308, 1909-1911. [CrossRef] [PubMed]
6. Sohal, R.S.; Weindruch, R. Oxidative stress, caloric restriction, and aging. Science 1996, 273, 59-63. [CrossRef] [PubMed]
7. Lopez-Miranda, J.; Perez-Jimenez, F.; Ros, E.; De Caterina, R.; Badimon, L.; Covas, M.I.; Escrich, E.; Ordovas, J.M.; Soriguer, F.; Abia, R.; et al. Olive oil and health: Summary of the ii international conference on olive oil and health consensus report, jaen and cordoba (Spain) 2008. Nutr. Metab. Cardiovasc. Dis. 2010, 20, 284-294. [CrossRef] [PubMed]
8. Visioli, F.; Galli, C. Biological properties of olive oil phytochemicals. Crit. Rev. Food Sci. Nutr. 2002, 42, 209-221. [CrossRef] [PubMed]
9. Giovanelli, L. Beneficial effects of olive oil phenols on the aging process. Experimental evidence and possible mechanisms of action. Nutr. Aging 2012, 1, 207-223.
10. Van Remmen, H.; Richardson, A. Oxidative damage to mitochondria and aging. Exp. Gerontol. 2001, 36, 957-968. [CrossRef]
11. Richter, C.; Park, J.W.; Ames, B.N. Normal oxidative damage to mitochondrial and nuclear DNA is extensive. Proc. Natl. Acad. Sci. USA 1988, 85, 6465-6467. [CrossRef] [PubMed]
12. Meissner, C.; Bruse, P.; Oehmichen, M. Tissue-specific deletion patterns of the mitochondrial genome with advancing age. Exp. Gerontol. 2006, 41, 518-524. [CrossRef] [PubMed]
13. Zapico, S.C.; Ubelaker, D.H. Relationship between mitochondrial DNA mutations and aging. Estimation of age-at-death. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2015. [CrossRef] [PubMed]
14. Srivastava, S.; Moraes, C.T. Double-strand breaks of mouse muscle mtdna promote large deletions similar to multiple mtdna deletions in humans. Hum. Mol. Genet. 2005, 14, 893-902. [CrossRef] [PubMed]
15. Quiles, J.L.; Ochoa, J.J.; Ramirez-Tortosa, C.; Battino, M.; Huertas, J.R.; Martin, Y.; Mataix, J. Dietary fat type (virgin olive vs. Sunflower oils) affects age-related changes in DNA double-strand-breaks, antioxidant capacity and blood lipids in rats. Exp. Gerontol. 2004, 39, 1189-1198. [CrossRef] [PubMed]
16. Quiles, J.L.; Ochoa, J.J.; Ramirez-Tortosa, C.; Huertas, J.R.; Mataix, J. Age-related mtdna deletion in rat liver depends on dietary fat unsaturation. J. Gerontol. 2006, 61A, 107-114. [CrossRef]
17. Fabiani, R.; Rosignoli, P.; de Bartolomeo, A.; Fuccelli, R.; Servili, M.; Montedoro, G.F.; Morozzi, G. Oxidative DNA damage is prevented by extracts of olive oil, hydroxytyrosol, and other olive phenolic compounds in human blood mononuclear cells and HL60 cells. J. Nutr. 2008, 138, 1411-1416. [PubMed]
18. Miro-Casas, E.; Covas, M.I.; Fito, M.; Farre-Albadalejo, M.; Marrugat, J.; de la Torre, R. Tyrosol and hydroxytyrosol are absorbed from moderate and sustained doses of virgin olive oil in humans. Eur. J. Clin. Nutr. 2003, 57, 186-190. [CrossRef] [PubMed]
19. Erol, O.; Arda, N.; Erdem, G. Phenols of virgin olive oil protects nuclear DNA against oxidative damage in hela cells. Food Chem. Toxicol. 2012, 50, 3475-3479. [CrossRef] [PubMed]
20. Blackburn, E.H. Structure and function of telomeres. Nature 1991, 350, 569-573. [CrossRef] [PubMed]
21. Blasco, M.A. Telomere length, stem cells and aging. Nat. Chem. Biol. 2007, 3, 640-649. [CrossRef] [PubMed]
22. Blasco, M.A. Telomeres and human disease: Ageing, cancer and beyond. Nat. Rev. Genet. 2005, 6, 611-622. [CrossRef] [PubMed]
23. Calado, R.T.; Young, N.S. Telomere diseases. N. Engl. J. Med. 2009, 361, 2353-2365. [CrossRef] [PubMed]
24. Haycock, P.C.; Heydon, E.E.; Kaptoge, S.; Butterworth, A.S.; Thompson, A.; Willeit, P. Leucocyte telomere length and risk of cardiovascular disease: Systematic review and meta-analysis. BMJ 2014, 349, g4227. [CrossRef] [PubMed]
25. Aviv, A.; Chen, W.; Gardner, J.P.; Kimura, M.; Brimacombe, M.; Cao, X.; Srinivasan, S.R.; Berenson, G.S. Leukocyte telomere dynamics: Longitudinal findings among young adults in the bogalusa heart study. Am. J. Epidemiol. 2009, 169, 323-329. [CrossRef] [PubMed]
26. Blackburn, E.H.; Greider, C.W.; Szostak, J.W. Telomeres and telomerase: The path from maize, tetrahymena and yeast to human cancer and aging. Nat. Med. 2006, 12, 1133-1138. [CrossRef] [PubMed]
27. Palm, W.; de Lange, T. How shelterin protects mammalian telomeres. Ann. Rev. Genet. 2008, 42, 301-334. [CrossRef] [PubMed]
28. Diez Roux, A.V.; Ranjit, N.; Jenny, N.S.; Shea, S.; Cushman, M.; Fitzpatrick, A.; Seeman, T. Race/ethnicity and telomere length in the multi-ethnic study of atherosclerosis. Aging Cell 2009, 8, 251-257. [CrossRef] [PubMed]
29. Adler, N.; Pantell, M.S.; O'Donovan, A.; Blackburn, E.; Cawthon, R.; Koster, A.; Opresko, P.; Newman, A.; Harris, T.B.; Epel, E. Educational attainment and late life telomere length in the health, aging and body composition study. Brain Behav. Immun. 2013, 27, 15-21. [CrossRef] [PubMed]
30. Carroll, J.E.; Diez-Roux, A.V.; Adler, N.E.; Seeman, T.E. Socioeconomic factors and leukocyte telomere length in a multi-ethnic sample: Findings from the multi-ethnic study of atherosclerosis (MESA). Brain Behav. Immun. 2013, 28, 108-114. [CrossRef] [PubMed]
31. Kiecolt-Glaser, J.K.; Epel, E.S.; Belury, M.A.; Andridge, R.; Lin, J.; Glaser, R.; Malarkey, W.B.; Hwang, B.S.; Blackburn, E. Omega-3 fatty acids, oxidative stress, and leukocyte telomere length: A randomized controlled trial. Brain behav. Immun. 2013, 28, 16-24. [CrossRef] [PubMed]
32. Du, M.; Prescott, J.; Kraft, P.; Han, J.; Giovannucci, E.; Hankinson, S.E.; de Vivo, I. Physical activity, sedentary behavior, and leukocyte telomere length in women. Am. J. Epidemiol. 2012, 175, 414-422. [CrossRef] [PubMed]
33. Okereke, O.I.; Prescott, J.; Wong, J.Y.; Han, J.; Rexrode, K.M.; de Vivo, I. High phobic anxiety is related to lower leukocyte telomere length in women. PLoS ONE 2012, 7, e40516. [CrossRef] [PubMed]
34. Prescott, J.; Du, M.; Wong, J.Y.Y.; Han, J.; de Vivo, I. Paternal age at birth is associated with offspring leukocyte telomere length in the nurses' health study. Hum. Reprod. 2012, 27, 3622-3631. [CrossRef] [PubMed]
35. Boccardi, V.; Esposito, A.; Rizzo, M.R.; Marfella, R.; Barbieri, M.; Paolisso, G. Mediterranean diet, telomere maintenance and health status among elderly. PLoS ONE 2013, 8, e62781.
36. Crous-Bou, M.; Fung, T.T.; Prescott, J.; Julin, B.; Du, M.; Sun, Q.; Rexrode, K.M.; Hu, F.B.; de Vivo, I. Mediterranean diet and telomere length in nurses' health study: Population based cohort study. BMJ 2014, 349, g6674. [CrossRef] [PubMed]
37. De Vos-Houben, J.M.J.; Ottenheim, N.R.; Kafatos, A.; Buijsse, B.; Hageman, G.J.; Kromhout, D.; Giltay, E.J. Telomere length, oxidative stress, and antioxidant status in elderly men in zutphen and crete. Mech. Ageing Dev. 2012, 133, 373-377. [CrossRef] [PubMed]
38. Gu, Y.; Honig, L.S.; Schupf, N.; Lee, J.H.; Luchsinger, J.A.; Stern, Y.; Scarmeas, N. Mediterranean diet and leukocyte telomere length in a multi-ethnic elderly population. Age 2015, 37, 24. [CrossRef] [PubMed]
39. Marin, C.; Delgado-Lista, J.; Ramirez, R.; Carracedo, J.; Caballero, J.; Perez-Martinez, P.; Gutierrez-Mariscal, F.M.; Garcia-Rios, A.; Delgado-Casado, N.; Cruz-Teno, C.; et al. Mediterranean diet reduces senescence-associated stress in endothelial cells. Age 2012, 34, 1309-1316. [CrossRef] [PubMed]
40. García-Calzón, S.; Gea, A.; Razquin, C.; Corella, D.; Lamuela-Raventós, R.M.; Martínez, J.A.; Martínez-González, M.A.; Zalba, G.; Marti, A. Longitudinal association of telomere length and obesity indices in an intervention study with a mediterranean diet: The predimed-navarra trial. Int. J. Obes. 2014, 38, 177-182. [CrossRef] [PubMed]
41. Armanios, M.; Blackburn, E.H. The telomere syndromes. Nat. Rev. Genet. 2012, 13, 693-704. [CrossRef] [PubMed]
42. Parzonko, A.; Czerwinska, M.E.; Kiss, A.K.; Naruszewicz, M. 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. [CrossRef] [PubMed]
43. Bird, A. Perceptions of epigenetics. Nature 2007, 447, 396-398. [CrossRef] [PubMed]
44. Zhi, D.; Aslibekyan, S.; Irvin, M.R.; Claas, S.A.; Borecki, I.B.; Ordovas, J.M.; Absher, D.M.; Arnett, D.K. SNPs located at CpG sites modulate genome-epigenome interaction. Epigenetics 2013, 8, 802-806. [CrossRef] [PubMed]
45. Campión, J.; Milagro, F.; Martinez, J.A. Epigenetics and obesity. Prog. Mol. Biol. Trans. Sci. 2009, 94, 291-347.
46. Di Francesco, A.; Falconi, A.; Di Germanio, C.; di Bonaventura, M.V.M.; Costa, A.; Caramuta, S.; del Carlo, M.; Compagnone, D.; Dainese, E.; Cifani, C.; et al. Extravirgin olive oil up-regulates CB 1 tumor suppressor gene in human colon cancer cells and in rat colon via epigenetic mechanisms. J. Nutr. Biochem. 2015, 26, 250-258. [CrossRef] [PubMed]
47. Shumaker, D.K.; Dechat, T.; Kohlmaier, A.; Adam, S.A.; Bozovsky, M.R.; Erdos, M.R.; Eriksson, M.; Goldman, A.E.; Khuon, S.; Collins, F.S.; et al. Mutant nuclear lamin a leads to progressive alterations of epigenetic control in premature aging. Proc. Natl. Acad. Sci. USA 2006, 103, 8703-8708. [CrossRef] [PubMed]
48. Osorio, F.G.; Varela, I.; Lara, E.; Puente, X.S.; Espada, J.; Santoro, R.; Freije, J.M.; Fraga, M.F.; Lopez-Otin, C. Nuclear envelope alterations generate an aging-like epigenetic pattern in mice deficient in Zmpste24 metalloprotease. Aging Cell 2010, 9, 947-957. [CrossRef] [PubMed]
49. Maegawa, S.; Hinkal, G.; Kim, H.S.; Shen, L.; Zhang, L.; Zhang, J.; Zhang, N.; Liang, S.; Donehower, L.A.; Issa, J.P. Widespread and tissue specific age-related DNA methylation changes in mice. Genome Res. 2010, 20, 332-340. [CrossRef] [PubMed]
50. Voisin, S.; Almén, M.S.; Moschonis, G.; Chrousos, G.P.; Manios, Y.; Schiöth, H.B. Dietary fat quality impacts genome-wide DNA methylation patterns in a cross-sectional study of greek preadolescents. Eur. J. Hum. Genet. 2015, 23, 654-662. [CrossRef] [PubMed]
51. Willett, W.C.; Sacks, F.; Trichopoulou, A.; Drescher, G.; Ferro-Luzzi, A.; Helsing, E.; Trichopoulos, D. Mediterranean diet pyramid: A cultural model for healthy eating. Am. J. Clin. Nutr. 1995, 61, 1402S-1406S. [PubMed]
52. Martín-Núñez, G.M.; Cabrera-Mulero, R.; Rubio-Martín, E.; Rojo-Martínez, G.; Olveira, G.; Valdés, S.; Soriguer, F.; Castaño, L.; Morcillo, S. Methylation levels of the SCD1 gene promoter and LINE-1 repeat region are associated with weight change: An intervention study. Mol. Nutr. Food Res. 2014, 58, 1528-1536. [CrossRef] [PubMed]
53. Oliveras-Ferraros, C.; Fernández-Arroyo, S.; Vazquez-Martin, A.; Lozano-Sánchez, J.; Cufí, S.; Joven, J.; Micol, V.; Fernández-Gutiérrez, A.; Segura-Carretero, A.; Menendez, J.A. Crude phenolic extracts from extra virgin olive oil circumvent de novo breast cancer resistance to HER1/HER2-targeting drugs by inducing GADD45-sensed cellular stress, G2/M arrest and hyperacetylation of histone H3. Int. J. Oncol. 2011, 38, 1533-1547. [PubMed]
54. Hoile, S.P.; Clarke-Harris, R.; Huang, R.C.; Calder, P.C.; Mori, T.A.; Beilin, L.J.; Lillycrop, K.A.; Burdge, G.C. Supplementation with N-3 long-chain polyunsaturated fatty acids or olive oil in men and women with renal disease induces differential changes in the DNA methylation of FADS2 and ELOVL5 in peripheral blood mononuclear cells. PLoS ONE 2014, 9, e109896. [CrossRef] [PubMed]
55. Hodson, L.; Fielding, B.A. Stearoyl-coa desaturase: Rogue or innocent bystander? Prog. Lipid Res. 2013, 52, 15-42. [CrossRef] [PubMed]
56. Schwenk, R.W.; Jonas, W.; Ernst, S.B.; Kammel, A.; Jähnert, M.; Schürmann, A. Diet-dependent alterations of hepatic scd1 expression are accompanied by differences in promoter methylation. Horm. Metab. Res. 2013, 45, 786-794. [CrossRef] [PubMed]
57. Ariyama, H.; Kono, N.; Matsuda, S.; Inoue, T.; Arai, H. Decrease in membrane phospholipid unsaturation induces unfolded protein response. J. Biol. Chem. 2010, 285, 22027-22035. [CrossRef] [PubMed]
58. Quiles, J.L.; Huertas, J.R.; Manas, M.; Battino, M.; Mataix, J. Physical exercise affects the lipid profile of mitochondrial membranes in rats fed with virgin olive oil or sunflower oil. Br. J. Nutr. 1999, 81, 21-24. [PubMed]
59. Milagro, F.I.; Gómez-Abellán, P.; Campión, J.; Martínez, J.A.; Ordovás, J.M.; Garaulet, M. Clock, PER2 and BMAL1 DNA methylation: Association with obesity and metabolic syndrome characteristics and monounsaturated fat intake. Chronobiol. Int. 2012, 29, 1180-1194. [CrossRef] [PubMed]
60. Cardinali, D.P.; Cano, P.; Jiménez-Ortega, V.; Esquifino, A.I. Melatonin and the metabolic syndrome: Physiopathologic and therapeutical implications. Neuroendocrinology 2011, 93, 133-142. [CrossRef] [PubMed]
61. Gómez-Santos, C.; Gómez-Abellán, P.; Madrid, J.A.; Hernández-Morante, J.J.; Lujan, J.A.; Ordovas, J.M.; Garaulet, M. Circadian rhythm of clock genes in human adipose explants. Obesity 2009, 17, 1481-1485. [CrossRef] [PubMed]
62. Mazeh, H.; Mizrahi, I.; Ilyayev, N.; Halle, D.; Brücher, B.L.D.M.; Bilchik, A.; Protic, M.; Daumer, M.; Stojadinovic, A.; Avital, I.; et al. The diagnostic and prognostic role of microrna in colorectal cancer-a comprehensive review. J. Cancer 2013, 4, 281-295. [CrossRef] [PubMed]
63. Bartel, D.P. Micrornas: Target recognition and regulatory functions. Cell 2009, 136, 215-233. [CrossRef] [PubMed]
64. Casas-Agustench, P.; Fernandes, F.S.; Tavares do Carmo, M.G.; Visioli, F.; Herrera, E.; Dávalos, A. Consumption of distinct dietary lipids during early pregnancy differentially modulates the expression of micrornas in mothers and offspring. PLoS ONE 2015, 10, e0117858.
65. Corella, D.; Ordovás, J.M. How does the mediterranean diet promote cardiovascular health? Current progress toward molecular mechanisms: Gene-diet interactions at the genomic, transcriptomic, and epigenomic levels provide novel insights into new mechanisms. Bioessays 2014, 36, 526-537. [CrossRef] [PubMed]
66. Hartl, F.U.; Bracher, A.; Hayer-Hartl, M. Molecular chaperones in protein folding and proteostasis. Nature 2011, 475, 324-332. [CrossRef] [PubMed]
67. Koga, H.; Kaushik, S.; Cuervo, A.M. Protein homeostasis and aging: The importance of exquisite quality control. Ageing Res. Rev. 2011, 10, 205-215. [CrossRef] [PubMed]
68. Mizushima, N.; Levine, B.; Cuervo, A.M.; Klionsky, D.J. Autophagy fights disease through cellular self-digestion. Nature 2008, 451, 1069-1075. [CrossRef] [PubMed]
69. Mayer, M.P.; Bukau, B. Hsp70 chaperones: Cellular functions and molecular mechanism. Cell. Mol. Life Sci. 2005, 62, 670-684. [CrossRef] [PubMed]
70. Brocchieri, L.; de Macario, E.C.; Macario, A.J.L. Hsp70 genes in the human genome: Conservation and differentiation patterns predict a wide array of overlapping and specialized functions. BMC Evol. Biol. 2008, 8, 19. [CrossRef] [PubMed]
71. Daugaard, M.; Rohde, M.; Jäättelä, M. The heat shock protein 70 family: Highly homologous proteins with overlapping and distinct functions. FEBS Lett. 2007, 581, 3702-3710. [CrossRef] [PubMed]
72. Neznanov, N.; Komarov, A.P.; Neznanova, L.; Stanhope-Baker, P.; Gudkov, A.V. Proteotoxic stress targeted therapy (PSTT): Induction of protein misfolding enhances the antitumor effect of the proteasome inhibitor bortezomib. Oncotarget 2011, 2, 209-221. [CrossRef] [PubMed]
73. Calderwood, S.K.; Murshid, A.; Prince, T. The shock of aging: Molecular chaperones and the heat shock response in longevity and aging-A mini-review. Gerontology 2009, 55, 550-558. [CrossRef] [PubMed]
74. Morrow, G.; Samson, M.; Michaud, S.; Tanguay, R.M. Overexpression of the small mitochondrial Hsp22 extends Drosophila life span and increases resistance to oxidative stress. FASEB J. 2004, 18, 598-599. [CrossRef] [PubMed]
75. Walker, G.A.; Lithgow, G.J. Lifespan extension in C. elegans by a molecular chaperone dependent upon insulin-like signals. Aging Cell 2003, 2, 131-139. [CrossRef] [PubMed]
76. Min, J.N.; Whaley, R.A.; Sharpless, N.E.; Lockyer, P.; Portbury, A.L.; Patterson, C. Chip deficiency decreases longevity, with accelerated aging phenotypes accompanied by altered protein quality control. Mol. Cell. Biol. 2008, 28, 4018-4025. [CrossRef] [PubMed]
77. Swindell, W.R.; Masternak, M.M.; Kopchick, J.J.; Conover, C.A.; Bartke, A.; Miller, R.A. Endocrine regulation of heat shock protein mRNA levels in long-lived dwarf mice. Mech. Ageing Dev. 2009, 130, 393-400. [CrossRef] [PubMed]
78. Powers, E.T.; Morimoto, R.I.; Dillin, A.; Kelly, J.W.; Balch, W.E. Biological and chemical approaches to diseases of proteostasis deficiency. Ann. Rev. Biochem. 2009, 78, 959-991. [CrossRef] [PubMed]
79. Daccache, A.; Lion, C.; Sibille, N.; Gerard, M.; Slomianny, C.; Lippens, G.; Cotelle, P. Oleuropein and derivatives from olives as tau aggregation inhibitors. Neurochem. Int. 2011, 58, 700-707. [CrossRef] [PubMed]
80. Rigacci, S.; Guidotti, V.; Bucciantini, M.; Parri, M.; Nediani, C.; Cerbai, E.; Stefani, M.; Berti, A. Oleuropein aglycon prevents cytotoxic amyloid aggregation of human amylin. J. Nutr. Biochem. 2010, 21, 726-735. [CrossRef] [PubMed]
81. Leung, T.K.; Rajendran, M.Y.; Monfries, C.; Hall, C.; Lim, L. The human heat-shock protein family. Expression of a novel heat-inducible Hsp70 (Hsp70b') and isolation of its cdna and genomic DNA. Biochem. J. 1990, 267, 125-132. [CrossRef] [PubMed]
82. Leung, T.K.C.; Hall, C.; Rajendran, M.; Spurr, N.K.; Lim, L. The human heat-shock genes Hspa6 and Hspa7 are both expressed and localize to chromosome 1. Genomics 1992, 12, 74-79. [CrossRef]
83. Noonan, E.J.; Place, R.F.; Giardina, C.; Hightower, L.E. Hsp70b' regulation and function. Cell Stress Chaperones 2007, 12, 219-229. [CrossRef] [PubMed]
84. Milner, C.M.; Campbell, R.D. Structure and expression of the three MHC-linked HSP70 genes. Immunogenetics 1990, 32, 242-251. [CrossRef] [PubMed]
85. Sargent, C.A.; Dunham, I.; Trowsdale, J.; Campbell, R.D. Human major histocompatibility complex contains genes for the major heat shock protein HSP70. Proc. Natl. Acad. Sci. USA 1989, 86, 1968-1972. [CrossRef] [PubMed]
86. Son, W.Y.; Hwang, S.H.; Han, C.T.; Lee, J.H.; Kim, S.; Kim, Y.C. Specific expression of heat shock protein HspA2 in human male germ cells. Mol. Hum. Reprod. 1999, 5, 1122-1126. [CrossRef] [PubMed]
87. Cañuelo, A.; Gilbert-López, B.; Pacheco-Liñán, P.; Martínez-Lara, E.; Siles, E.; Miranda-Vizuete, A. Tyrosol, a main phenol present in extra virgin olive oil, increases lifespan and stress resistance in caenorhabditis elegans. Mech. Ageing Dev. 2012, 133, 563-574. [CrossRef] [PubMed]
88. Chiang, W.C.; Ching, T.T.; Lee, H.C.; Mousigian, C.; Hsu, A.L. HSF-1 regulators DDL-1/2 link insulin-like signaling to heat-shock responses and modulation of longevity. Cell 2012, 148, 322-334. [CrossRef] [PubMed]
89. Hsu, A.L.; Murphy, C.T.; Kenyon, C. Regulation of aging and age-related disease by DAF-16 and heat-shock factor. Science 2003, 300, 1142-1145. [CrossRef] [PubMed]
90. Westerheide, S.D.; Anckar, J.; Stevens, S.M., Jr.; Sistonen, L.; Morimoto, R.I. Stress-inducible regulation of heat shock factor 1 by the deacetylase SIRT1. Science 2009, 323, 1063-1066. [CrossRef] [PubMed]
91. Lam, E.W.; Francis, R.E.; Petkovic, M. Foxo transcription factors: Key regulators of cell fate. Biochem. Soc. Trans. 2006, 34, 722-726. [CrossRef] [PubMed]
92. Arden, K.C.; Biggs, W.H., III. Regulation of the foxo family of transcription factors by phosphatidylinositol-3 kinase-activated signaling. Arch. Biochem. Biophys. 2002, 403, 292-298. [CrossRef]
93. Lim, J.H.; Gerhart-Hines, Z.; Dominy, J.E.; Lee, Y.; Kim, S.; Tabata, M.; Xiang, Y.K.; Puigserver, P. Oleic acid stimulates complete oxidation of fatty acids through protein kinase A-dependent activation of sirt1-pgc1α complex. J. Biol. Chem. 2013, 288, 7117-7126. [CrossRef] [PubMed]
94. Katsiki, M.; Chondrogianni, N.; Chinou, I.; Rivett, A.J.; Gonos, E.S. 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. [CrossRef] [PubMed]
95. Bullon, P.; Battino, M.; Varela-Lopez, A.; Perez-Lopez, P.; Granados-Principal, S.; Ramirez-Tortosa, M.C.; Ochoa, J.J.; Cordero, M.D.; Gonzalez-Alonso, A.; Ramirez-Tortosa, C.L.; et al. Diets based on virgin olive oil or fish oil but not on sunflower oil prevent age-related alveolar bone resorption by mitochondrial-related mechanisms. PLoS ONE 2013, 8, e74234.
96. Oliván, S.; Martínez-Beamonte, R.; Calvo, A.C.; Surra, J.C.; Manzano, R.; Arnal, C.; Osta, R.; Osada, J. Extra virgin olive oil intake delays the development of amyotrophic lateral sclerosis associated with reduced reticulum stress and autophagy in muscle of SOD1G93A mice. J. Nutr. Biochem. 2014, 25, 885-892. [CrossRef] [PubMed]
97. Blagosklonny, M.V. Aging: Ros or tor. Cell Cycle 2008, 7, 3344-3354. [CrossRef] [PubMed]
98. Harrison, D.E.; Strong, R.; Sharp, Z.D.; Nelson, J.F.; Astle, C.M.; Flurkey, K.; Nadon, N.L.; Wilkinson, J.E.; Frenkel, K.; Carter, C.S.; et al. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature 2009, 460, 392-395. [CrossRef] [PubMed]
99. Wilkinson, J.E.; Burmeister, L.; Brooks, S.V.; Chan, C.C.; Friedline, S.; Harrison, D.E.; Hejtmancik, J.F.; Nadon, N.; Strong, R.; Wood, L.K.; et al. Rapamycin slows aging in mice. Aging Cell 2012, 11, 675-682. [CrossRef] [PubMed]
100. Zou, X.; Feng, Z.; Li, Y.; Wang, Y.; Wertz, K.; Weber, P.; Fu, Y.; Liu, J. 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. [CrossRef] [PubMed]
101. Pluquet, O.; Pourtier, A.; Abbadie, C. The unfolded protein response and cellular senescence. A review in the theme: Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. Am. J. Physiol. Cell Physiol. 2015, 308, C415-C425. [CrossRef] [PubMed]
102. Kroemer, G.; Mariño, G.; Levine, B. Autophagy and the integrated stress response. Mol. Cell 2010, 40, 280-293. [CrossRef] [PubMed]
103. Sommerweiss, D.; Gorski, T.; Richter, S.; Garten, A.; Kiess, W. Oleate rescues INS-1E β-cells from palmitate-induced apoptosis by preventing activation of the unfolded protein response. Biochem. Biophys. Res. Commun. 2013, 441, 770-776. [CrossRef] [PubMed]
104. Sieber, J.; Lindenmeyer, M.T.; Kampe, K.; Campbell, K.N.; Cohen, C.D.; Hopfer, H.; Mundel, P.; Jehle, A.W. Regulation of podocyte survival and endoplasmic reticulum stress by fatty acids. Am. J. Physiol. Ren. Physiol. 2010, 299, F821-F829. [CrossRef] [PubMed]
105. Matos, L.; Gouveia, A.M.; Almeida, H. Er stress response in human cellular models of senescence. J. Gerontol. Ser. A Biol. Sci. Med. Sci. 2015, 70, 924-935. [CrossRef] [PubMed]
106. Benvenuti, S.; Cramer, R.; Quinn, C.C.; Bruce, J.; Zvelebil, M.; Corless, S.; Bond, J.; Yang, A.; Hockfield, S.; Burlingame, A.L.; et al. Differential proteome analysis of replicative senescence in rat embryo fibroblasts. Mol. Cell. Proteom. 2002, 1, 280-292. [CrossRef]
107. Dörr, J.R.; Yu, Y.; Milanovic, M.; Beuster, G.; Zasada, C.; Däbritz, J.H.M.; Lisec, J.; Lenze, D.; Gerhardt, A.; Schleicher, K.; et al. Synthetic lethal metabolic targeting of cellular senescence in cancer therapy. Nature 2013, 501, 421-425. [CrossRef] [PubMed]
108. Panganiban, R.A.M.; Mungunsukh, O.; Day, R.M. X-irradiation induces er stress, apoptosis, and senescence in pulmonary artery endothelial cells. Int. J. Radiat. Biol. 2013, 89, 656-667. [CrossRef] [PubMed]
109. Green, C.D.; Olson, L.K. Modulation of palmitate-induced endoplasmic reticulum stress and apoptosis in pancreatic β-cells by stearoyl-coa desaturase and elovl6. Am. J. Physiol. Endocrinol. Metab. 2011, 300, E640-E649. [CrossRef] [PubMed]
110. Svärd, M.; Biterova, E.I.; Bourhis, J.-M.; Guy, J.E. The crystal structure of the human co-chaperone P58 (IPK). PLoS ONE 2011, 6, e22337.
111. Yan, W.; Frank, C.L.; Korth, M.J.; Sopher, B.L.; Novoa, I.; Ron, D.; Katze, M.G. Control of PERK eIF2α kinase activity by the endoplasmic reticulum stress-induced molecular chaperone p58ipk. Proc. Natl. Acad. Sci. USA 2002, 99, 15920-15925. [CrossRef] [PubMed]
112. Wiseman, R.L.; Haynes, C.M.; Ron, D. Snapshot: The unfolded protein response. Cell 2010, 140, e590-e592. [CrossRef] [PubMed]
113. Ron, D.; Walter, P. Signal integration in the endoplasmic reticulum unfolded protein response. Nat. Rev. Mol. Cell Biol. 2007, 8, 519-529. [CrossRef] [PubMed]
114. Zhang, X.; Cao, J.; Zhong, L. Hydroxytyrosol inhibits pro-inflammatory cytokines, iNOS, and COX-2 expression in human monocytic cells. Naunyn Schmiedeberg's Arch. Pharmacol. 2009, 379, 581-586. [CrossRef] [PubMed]
115. Lozano-Sánchez, J.; Segura-Carretero, A.; Menendez, J.A.; Oliveras-Ferraros, C.; Cerretani, L.; Fernández-Gutiérrez, A. Prediction of extra virgin olive oil varieties through their phenolic profile. Potential cytotoxic activity against human breast cancer cells. J. Agric. Food Chem. 2010, 58, 9942-9955. [CrossRef] [PubMed]
116. Menendez, J.A.; Joven, J.; Aragonès, G.; Barrajón-Catalán, E.; Beltrán-Debón, R.; Borrás-Linares, I.; Camps, J.; Corominas-Faja, B.; Cufí, S.; Fernández-Arroyo, S.; 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. [CrossRef] [PubMed]
117. Barzilai, N.; Huffman, D.M.; Muzumdar, R.H.; Bartke, A. The critical role of metabolic pathways in aging. Diabetes 2012, 61, 1315-1322. [CrossRef] [PubMed]
118. Fontana, L.; Partridge, L.; Longo, V.D. Dietary restriction, growth factors and aging: From yeast to humans. Science 2010, 328, 321-326. [CrossRef] [PubMed]
119. Schumacher, B.; van der Pluijm, I.; Moorhouse, M.J.; Kosteas, T.; Robinson, A.R.; Suh, Y.; Breit, T.M.; van Steeg, H.; Niedernhofer, L.J.; van Ijcken, W.; et al. Delayed and accelerated aging share common longevity assurance mechanisms. PLoS Genet. 2008, 4, e1000161. [CrossRef] [PubMed]
120. Garinis, G.A.; van der Horst, G.T.; Vijg, J.; Hoeijmakers, J.H. DNA damage and ageing: New-age ideas for an age-old problem. Nat. Cell Biol. 2008, 10, 1241-1247. [CrossRef] [PubMed]
121. Rincon, M.; Rudin, E.; Barzilai, N. The insulin/IGF-1 signaling in mammals and its relevance to human longevity. Exp. Gerontol. 2005, 40, 873-877. [CrossRef] [PubMed]
122. Gonzalez, M.; Zarzuelo, A.; Gamez, M.J.; Utrilla, M.P.; Jimenez, J.; Osuna, I. Hypoglycemic activity of olive leaf. Planta Med. 1992, 58, 513-515. [CrossRef] [PubMed]
123. Al-Azzawie, H.F.; Alhamdani, M.S.S. Hypoglycemic and antioxidant effect of oleuropein in alloxan-diabetic rabbits. Life Sci. 2006, 78, 1371-1377. [CrossRef] [PubMed]
124. Hamden, K.; Allouche, N.; Damak, M.; Elfeki, A. Hypoglycemic and antioxidant effects of phenolic extracts and purified hydroxytyrosol from olive mill waste in vitro and in rats. Chem. Biol. Interact. 2009, 180, 421-432. [CrossRef] [PubMed]
125. Jemai, H.; el Feki, A.; Sayadi, S. Antidiabetic and antioxidant effects of hydroxytyrosol and oleuropein from olive leaves in alloxan-diabetic rats. J. Agric. Food Chem. 2009, 57, 8798-8804. [CrossRef] [PubMed]
126. De Bock, M.; Derraik, J.G.; Brennan, C.M.; Biggs, J.B.; Morgan, P.E.; Hodgkinson, S.C.; Hofman, P.L.; Cutfield, W.S. Olive (Olea europaea L.) leaf polyphenols improve insulin sensitivity in middle-aged overweight men: A randomized, placebo-controlled, crossover trial. PLoS ONE 2013, 8, e57622.
127. Johnson, S.C.; Rabinovitch, P.S.; Kaeberlein, M. mTOR is a key modulator of ageing and age-related disease. Nature 2013, 493, 338-345. [CrossRef] [PubMed]
128. Meric-Bernstam, F.; Gonzalez-Angulo, A.M. Targeting the mtor signaling network for cancer therapy. J. Clin. Oncol. 2009, 27, 2278-2287. [CrossRef] [PubMed]
129. Engelman, J.A. Targeting PI3K signalling in cancer: Opportunities, challenges and limitations. Nat. Rev. Cancer 2009, 9, 550-562. [CrossRef] [PubMed]
130. Caccamo, A.; Majumder, S.; Richardson, A.; Strong, R.; Oddo, S. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-β, and Tau: Effects on cognitive impairments. J. Biol. Chem. 2010, 285, 13107-13120. [CrossRef] [PubMed]
131. Chano, T.; Okabe, H.; Hulette, C.M. RB1CC1 insufficiency causes neuronal atrophy through mTOR signaling alteration and involved in the pathology of Alzheimer's diseases. Brain Res. 2007, 1168, 97-105. [CrossRef] [PubMed]
132. Zoncu, R.; Sabatini, D.M.; Efeyan, A. mTOR: From growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol. 2011, 12, 21-35. [CrossRef] [PubMed]
133. Don, A.S.; Zheng, X.F. Recent clinical trials of mtor-targeted cancer therapies. Rev. Recent Clin. Trials 2011, 6, 24-35. [PubMed]
134. Shaw, B.; Lambert, S.; Wong, M.H.; Ralston, J.C.; Stryjecki, C.; Mutch, D.M. Individual saturated and monounsaturated fatty acids trigger distinct transcriptional networks in differentiated 3T3-L1 preadipocytes. J. Nutrigenet. Nutrigenom. 2013, 6, 1-15. [CrossRef] [PubMed]
135. Khanfar, M.A.; Bardaweel, S.K.; Akl, M.R.; el Sayed, K.A. Olive oil-derived oleocanthal as potent inhibitor of mammalian target of rapamycin: Biological evaluation and molecular modeling studies. Phytother. Res. 2015, 29, 1776-1782. [CrossRef] [PubMed]
136. Harman, D. Aging: A theory based on free radical and radiation chemistry. J. Gerontol. 1956, 11, 298-300. [CrossRef] [PubMed]
137. Hekimi, S.; Lapointe, J.; Wen, Y. Taking a "good" look at free radicals in the aging process. Trends Cell Biol. 2011, 21, 569-576. [CrossRef] [PubMed]
138. Sena, L.A.; Chandel, N.S. Physiological roles of mitochondrial reactive oxygen species. Mol. Cell 2012, 48, 158-167. [CrossRef] [PubMed]
139. Quiles, J.L.; Huertas, J.R.; Manas, M.; Ochoa, J.J.; Battino, M.; Mataix, J. Oxidative stress induced by exercise and dietary fat modulates the coenzyme q and vitamin a balance between plasma and mitochondria. Int. J. Vitam. Nutr. Res. 1999, 69, 243-249. [CrossRef] [PubMed]
140. Mataix, J.; Ochoa, J.J.; Quiles, J.L. Olive oil and mitochondrial oxidative stress. International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. J. Int. Vitaminol. Nutr. 2006, 76, 178-183. [CrossRef] [PubMed]
141. Quiles, J.L.; Martinez, E.; Ibanez, S.; Ochoa, J.J.; Martin, Y.; Lopez-Frias, M.; Huertas, J.R.; Mataix, J. Ageing-related tissue-specific alterations in mitochondrial composition and function are modulated by dietary fat type in the rat. J. Bioenerget. Biomembr. 2002, 34, 517-524. [CrossRef]
142. Ochoa, J.J.; Quiles, J.L.; Ibanez, S.; Martinez, E.; Lopez-Frias, M.; Huertas, J.R.; Mataix, J. Aging-related oxidative stress depends on dietary lipid source in rat postmitotic tissues. J. Bioenerget. Biomembr. 2003, 35, 267-275. [CrossRef]
143. Barja, G. Rate of generation of oxidative stress-related damage and animal longevity. Free Radic. Biol. Med. 2002, 33, 1167-1172. [CrossRef]
144. Van der Loo, B.; Labugger, R.; Aebischer, C.P.; Skepper, J.N.; Bachschmid, M.; Spitzer, V.; Kilo, J.; Altwegg, L.; Ullrich, V.; Luscher, T.F. Cardiovascular aging is associated with vitamin E increase. Circulation 2002, 105, 1635-1638. [CrossRef] [PubMed]
145. Beckman, K.B.; Ames, B.N. The free radical theory of aging matures. Physiol. Rev. 1998, 78, 547-581. [PubMed]
146. Brown-Borg, H.M.; Rakoczy, S.G. Catalase expression in delayed and premature aging mouse models. Exp. Gerontol. 2000, 35, 199-212. [CrossRef]
147. Bronnikov, G.E.; Kulagina, T.P.; Aripovskii, A.V.; Kramarova, L.I. Correction of mitochondrial enzyme activities in the skeletal muscles of old rats in response to addition of olive oil to the ration. Bull. Exp. Biol. Med. 2015, 159, 266-268. [CrossRef] [PubMed]
148. Jeck, W.R.; Siebold, A.P.; Sharpless, N.E. Review: A meta-analysis of gwas studies and age-associated diseases. Aging Cell 2012, 11, 727-731. [CrossRef] [PubMed]
149. Hebert, L.E.; Scherr, P.A.; Bienias, J.L.; Bennett, D.A.; Evans, D.A. State-specific projections through 2025 of Alzheimer disease prevalence. Neurology 2004, 62, 1645. [CrossRef] [PubMed]
150. Panza, F.; Solfrizzi, V.; Colacicco, A.M.; D'Introno, A.; Capurso, C.; Torres, F.; del Parigi, A.; Capurso, S.; Capurso, A. Mediterranean diet and cognitive decline. Public Health Nutr. 2004, 7, 959-963. [CrossRef] [PubMed]
151. Solfrizzi, V.; Panza, F.; Capurso, A. The role of diet in cognitive decline. J. Neural Transm. 2003, 110, 95-110. [PubMed]
152. Scarmeas, N.; Luchsinger, J.A.; Schupf, N.; Brickman, A.M.; Cosentino, S.; Tang, M.X.; Stern, Y. Physical activity, diet, and risk of Alzheimer disease. JAMA 2009, 302, 627-637. [CrossRef] [PubMed]
153. Beauchamp, G.K.; Keast, R.S.; Morel, D.; Lin, J.; Pika, J.; Han, Q.; Lee, C.H.; Smith, A.B.; Breslin, P.A. Phytochemistry: Ibuprofen-like activity in extra-virgin olive oil. Nature 2005, 437, 45-46. [CrossRef] [PubMed]
154. Umeno, A.; Takashima, M.; Murotomi, K.; Nakajima, Y.; Koike, T.; Matsuo, T.; Yoshida, Y. Radical-scavenging activity and antioxidative effects of olive leaf components oleuropein and hydroxytyrosol in comparison with homovanillic alcohol. J. Oleo Sci. 2015, 64, 793-800. [CrossRef] [PubMed]
155. Visioli, F.; Bellomo, G.; Galli, C. Free radical-scavenging properties of olive oil polyphenols. Biochem. Biophys. Res. Commun. 1998, 247, 60-64. [CrossRef] [PubMed]
156. Rodríguez-Morató, J.; Xicota, L.; Fitó, M.; Farré, M.; Dierssen, M.; de la Torre, R. Potential role of olive oil phenolic compounds in the prevention of neurodegenerative diseases. Molecules 2015, 20, 4655-4680. [CrossRef] [PubMed]
157. Hardy, J. The amyloid hypothesis for Alzheimer's disease: A critical reappraisal. J. Neurochem. 2009, 110, 1129-1134. [CrossRef] [PubMed]
158. Lam, F.C.; Liu, R.; Lu, P.; Shapiro, A.B.; Renoir, J.M.; Sharom, F.J.; Reiner, P.B. β-amyloid efflux mediated by p-glycoprotein. J. Neurochem. 2001, 76, 1121-1128. [CrossRef] [PubMed]
159. Iqbal, K.; Liu, F.; Gong, C.X.; Alonso Adel, C.; Grundke-Iqbal, I. Mechanisms of Tau-induced neurodegeneration. Acta Neuropathol. 2009, 118, 53-69. [CrossRef] [PubMed]
160. Abuznait, A.H.; Cain, C.; Ingram, D.; Burk, D.; Kaddoumi, A. Up-regulation of p-glycoprotein reduces intracellular accumulation of beta amyloid: Investigation of p-glycoprotein as a novel therapeutic target for alzheimer's disease. J. Pharm. Pharmacol. 2011, 63, 1111-1118. [CrossRef] [PubMed]
161. Hardy, J. A hundred years of alzheimer's disease research. Neuron 2006, 52, 3-13. [CrossRef] [PubMed]
162. Okuyama, K.; Nishiura, C.; Mizushima, F.; Minoura, K.; Sumida, M.; Taniguchi, T.; Tomoo, K.; Ishida, T. Linkage-dependent contribution of repeat peptides to self-aggregation of three- or four-repeat microtubule-binding domains in tau protein. FEBS J. 2008, 275, 1529-1539. [CrossRef] [PubMed]
163. Mukrasch, M.D.; Biernat, J.; von Bergen, M.; Griesinger, C.; Mandelkow, E.; Zweckstetter, M. Sites of Tau important for aggregation populate β-structure and bind to microtubules and polyanions. J. Biol. Chem. 2005, 280, 24978-24986. [CrossRef] [PubMed]
164. Alonso, A.D.; di Clerico, J.; Li, B.; Corbo, C.P.; Alaniz, M.E.; Grundke-Iqbal, I.; Iqbal, K. Phosphorylation of Tau at Thr212, Thr231, and Ser262 combined causes neurodegeneration. J. Biol. Chem. 2010, 285, 30851-30860. [CrossRef] [PubMed]
165. Li, W.; Lee, V.M. Characterization of two vqixxk motifs for tau fibrillization in vitro. Biochemistry 2006, 45, 15692-15701. [CrossRef] [PubMed]
166. Li, W.; Sperry, J.B.; Crowe, A.; Trojanowski, J.Q.; Smith, A.B., III; Lee, V.M. Inhibition of Tau fibrillization by oleocanthal via reaction with the amino groups of Tau. J. Neurochem. 2009, 110, 1339-1351. [CrossRef] [PubMed]
167. Monti, M.C.; Margarucci, L.; Tosco, A.; Riccio, R.; Casapullo, A. New insights on the interaction mechanism between tau protein and oleocanthal, an extra-virgin olive-oil bioactive component. Food Funct. 2011, 2, 423-428. [CrossRef] [PubMed]
168. Monti, M.C.; Margarucci, L.; Riccio, R.; Casapullo, A. Modulation of tau protein fibrillization by oleocanthal. J. Nat. Prod. 2012, 75, 1584-1588. [CrossRef] [PubMed]
169. Abuznait, A.H.; Qosa, H.; Busnena, B.A.; el Sayed, K.A.; Kaddoumi, A. Olive-oil-derived oleocanthal enhances beta-amyloid clearance as a potential neuroprotective mechanism against Alzheimer's disease: In vitro and in vivo studies. ACS Chem. Neurosci. 2013, 4, 973-982. [CrossRef] [PubMed]
170. Qosa, H.; Mohamed, L.A.; Batarseh, Y.S.; Alqahtani, S.; Ibrahim, B.; LeVine, H., III; Keller, J.N.; Kaddoumi, A. Extra-virgin olive oil attenuates amyloid-β and tau pathologies in the brains of tgswdi mice. J. Nutr. Biochem. 2015, 26, 1479-1490. [CrossRef] [PubMed]
171. Davis, J.; Xu, F.; Deane, R.; Romanov, G.; Previti, M.L.; Zeigler, K.; Zlokovic, B.V.; van Nostrand, W.E. Early-onset and robust cerebral microvascular accumulation of amyloid β-protein in transgenic mice expressing low levels of a vasculotropic dutch/iowa mutant form of amyloid beta-protein precursor. J. Biol. Chem. 2004, 279, 20296-20306. [CrossRef] [PubMed]
172. Kline, A. Apolipoprotein e, amyloid-ss clearance and therapeutic opportunities in Alzheimer's disease. Alzheimer's Res. Ther. 2012, 4, 32. [CrossRef] [PubMed]
173. Wildsmith, K.R.; Holley, M.; Savage, J.C.; Skerrett, R.; Landreth, G.E. Evidence for impaired amyloid β clearance in Alzheimer's disease. Alzheimer's Res. Ther. 2013, 5, 33. [CrossRef] [PubMed]
174. Qosa, H.; Batarseh, Y.S.; Mohyeldin, M.M.; el Sayed, K.A.; Keller, J.N.; Kaddoumi, A. Oleocanthal enhances amyloid-beta clearance from the brains of TgSwDI mice and in vitro across a human blood-brain barrier model. ACS Chem. Neurosci. 2015, 6, 1849-1859. [CrossRef] [PubMed]
175. Verkhratsky, A.; Rodriguez, J.J.; Steardo, L. Astrogliopathology: A central element of neuropsychiatric diseases? Neuroscientist 2014, 20, 576-588. [CrossRef] [PubMed]
176. Heppner, F.L.; Ransohoff, R.M.; Becher, B. Immune attack: The role of inflammation in Alzheimer disease. Nat. Rev. Neurosci. 2015, 16, 358-372. [CrossRef] [PubMed]
177. Tong, L.; Balazs, R.; Soiampornkul, R.; Thangnipon, W.; Cotman, C.W. Interleukin-1β a impairs brain derived neurotrophic factor-induced signal transduction. Neurobiol. Aging 2008, 29, 1380-1393. [CrossRef] [PubMed]
178. Gruber, R.; Koch, H.; Doll, B.A.; Tegtmeier, F.; Einhorn, T.A.; Hollinger, J.O. Fracture healing in the elderly patient. Exp. Gerontol. 2006, 41, 1080-1093. [CrossRef] [PubMed]
179. Moerman, E.J.; Teng, K.; Lipschitz, D.A.; Lecka-Czernik, B. Aging activates adipogenic and suppresses osteogenic programs in mesenchymal marrow stroma/stem cells: The role of PPAR-2 transcription factor and TGF-β/BMP signaling pathways. Aging Cell 2004, 3, 379-389. [CrossRef] [PubMed]
180. Duque, G. Bone and fat connection in aging bone. Curr. Opin. Rheumatol. 2008, 20, 429-434. [CrossRef] [PubMed]
181. Santiago-Mora, R.; Casado-Diaz, A.; de Castro, M.D.; Quesada-Gomez, J.M. Oleuropein enhances osteoblastogenesis and inhibits adipogenesis: The effect on differentiation in stem cells derived from bone marrow. Osteoporos. Int. 2011, 22, 675-684. [CrossRef] [PubMed]
182. Franco, M.N.; Galeano-Diaz, T.; Lopez, O.; Fernandez-Bolanos, J.G.; Sanchez, J.; de Miguel, C.; Gil, M.V.; Martin-Vertedor, D. Phenolic compounds and antioxidant capacity of virgin olive oil. Food Chem. 2014, 163, 289-298. [CrossRef] [PubMed]
183. Bandyopadhyay, S.; Lion, J.M.; Mentaverri, R.; Ricupero, D.A.; Kamel, S.; Romero, J.R.; Chattopadhyay, N. Attenuation of osteoclastogenesis and osteoclast function by apigenin. Biochem. Pharmacol. 2006, 72, 184-197. [CrossRef] [PubMed]
184. Liu, H.; Huang, H.; Li, B.; Wu, D.; Wang, F.; Zheng, X.; Chen, Q.; Wu, B.; Fan, X. Olive oil in the prevention and treatment of osteoporosis after artificial menopause. Clin. Interv. Aging 2014, 9, 2087-2095. [CrossRef] [PubMed]
185. Shaw, A.C.; Joshi, S.; Greenwood, H.; Panda, A.; Lord, J.M. Aging of the innate immune system. Curr. Opin. Immunol. 2010, 22, 507-513. [CrossRef] [PubMed]
186. Aldelhay, E.; Pizzatti, L.; Binato, R. Networks establishing hepatopoietic stem cell multipotency and self-renewal. In Advances in Hematopoietic Stem Cell Research; Pelayo, R., Ed.; InTech: Vienna, Austria, 2012; pp. 3-38.
187. Samet, I. Effect of olive leaf components on the proliferation and viability of hematopoietic stem cells. Asian J. Biomed. Pharm. Sci. 2014, 4, 1-7. [CrossRef]
188. Cardoso, C.R.; Favoreto, S., Jr.; Oliveira, L.L.; Vancim, J.O.; Barban, G.B.; Ferraz, D.B.; Silva, J.S. Oleic acid modulation of the immune response in wound healing: A new approach for skin repair. Immunobiology 2011, 216, 409-415. [CrossRef] [PubMed]
189. Jung, Y.H.; Lee, S.J.; Oh, S.Y.; Lee, H.J.; Ryu, J.M.; Han, H.J. Oleic acid enhances the motility of umbilical cord blood derived mesenchymal stem cells through EphB2-dependent F-actin formation. Biochim. Biophys. Acta 2015, 1853, 1905-1917. [CrossRef] [PubMed]
190. Gulati, R.; Jevremovic, D.; Peterson, T.E.; Witt, T.A.; Kleppe, L.S.; Mueske, C.S.; Lerman, A.; Vile, R.G.; Simari, R.D. Autologous culture-modified mononuclear cells confer vascular protection after arterial injury. Circulation 2003, 108, 1520-1526. [CrossRef] [PubMed]
191. Levonen, A.L.; Inkala, M.; Heikura, T.; Jauhiainen, S.; Jyrkkanen, H.K.; Kansanen, E.; Maatta, K.; Romppanen, E.; Turunen, P.; Rutanen, J.; et al. Nrf2 gene transfer induces antioxidant enzymes and suppresses smooth muscle cell growth in vitro and reduces oxidative stress in rabbit aorta in vivo. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 741-747. [CrossRef] [PubMed]
192. Dulak, J.; Loboda, A.; Jozkowicz, A. Effect of heme oxygenase-1 on vascular function and disease. Curr. Opin. Lipidol. 2008, 19, 505-512. [CrossRef] [PubMed]
193. Rosignoli, P.; Fuccelli, R.; Fabiani, R.; Servili, M.; Morozzi, G. Effect of olive oil phenols on the production of inflammatory mediators in freshly isolated human monocytes. J. Nutr. Biochem. 2013, 24, 1513-1519. [CrossRef] [PubMed]
194. Frasca, D.; Blomberg, B.B. Inflammaging decreases adaptive and innate immune responses in mice and humans. Biogerontology 2016, 17, 7-19. [CrossRef] [PubMed]
195. Maiuri, M.C.; de Stefano, D.; di Meglio, P.; Irace, C.; Savarese, M.; Sacchi, R.; Cinelli, M.P.; Carnuccio, R. Hydroxytyrosol, a phenolic compound from virgin olive oil, prevents macrophage activation. Naunyn Schmiedeberg's Arch. Pharmacol. 2005, 371, 457-465. [CrossRef] [PubMed]
196. Dell'Agli, M.; Fagnani, R.; Galli, G.V.; Maschi, O.; Gilardi, F.; Ballosta, E.; Crestani, M.; Bosisio, E.; de Fabiani, E.; Caruso, D. Olive oil phenols modulate the expression of metalloproteinase 9 in Thp-1 cells by acting on nfkb signalling. J. Agric. Food Chem. 2010, 58, 2246-2252. [CrossRef] [PubMed]
197. Arango, D.; Diosa-Toro, M.; Rojas-Hernandez, L.S.; Cooperstone, J.L.; Schwartz, S.J.; Mo, X.; Jiang, J.; Schmittgen, T.D.; Doseff, A.I. Dietary apigenin reduces LPS-induced expression of miR-155 restoring immune balance during inflammation. Mol. Nutr. Food Res. 2015, 59, 763-772. [CrossRef] [PubMed]
198. Dell'Agli, M.; Fagnani, R.; Mitro, N.; Scurati, S.; Masciadri, M.; Mussoni, L.; Galli, G.V.; Bosisio, E.; Crestani, M.; de Fabiani, E.; et al. Minor components of olive oil modulate proatherogenic adhesion molecules involved in endothelial activation. J. Agric. Food Chem. 2006, 54, 3259-3264. [CrossRef] [PubMed]
199. Zambonin, L.; Caliceti, C.; Vieceli Dalla Sega, F.; Fiorentini, D.; Hrelia, S.; Landi, L.; Prata, C. Dietary phenolic acids act as effective antioxidants in membrane models and in cultured cells, exhibiting proapoptotic effects in leukaemia cells. Oxid. Med. Cell. Longev. 2012, 2012, 839298. [CrossRef] [PubMed]
200. Meza-Miranda, E.R.; Rangel-Zuniga, O.A.; Marin, C.; Perez-Martinez, P.; Delgado-Lista, J.; Haro, C.; Pena-Orihuela, P.; Jimenez-Morales, A.I.; Malagon, M.M.; Tinahones, F.J.; et al. Virgin olive oil rich in phenolic compounds modulates the expression of atherosclerosis-related genes in vascular endothelium. Eur. J. Nutr. 2015. [CrossRef] [PubMed]
201. Santos-Gonzalez, M.; Lopez-Miranda, J.; Perez-Jimenez, F.; Navas, P.; Villalba, J.M. Dietary oil modifies the plasma proteome during aging in the rat. Age 2012, 34, 341-358. [CrossRef] [PubMed]
202. Cunha, T.M.; Verri, W.A., Jr.; Silva, J.S.; Poole, S.; Cunha, F.Q.; Ferreira, S.H. A cascade of cytokines mediates mechanical inflammatory hypernociception in mice. Proc. Natl. Acad. Sci. USA 2005, 102, 1755-1760. [CrossRef] [PubMed]
203. Gong, D.; Geng, C.; Jiang, L.; Cao, J.; Yoshimura, H.; Zhong, L. Effects of hydroxytyrosol-20 on carrageenan-induced acute inflammation and hyperalgesia in rats. Phytother. Res. 2009, 23, 646-650. [CrossRef] [PubMed]
204. Sanchez-Fidalgo, S.; Sanchez de Ibarguen, L.; Cardeno, A.; Alarcon de la Lastra, C. Influence of extra virgin olive oil diet enriched with hydroxytyrosol in a chronic dss colitis model. Eur. J. Nutr. 2012, 51, 497-506. [CrossRef] [PubMed]
205. Silva, S.; Sepodes, B.; Rocha, J.; Direito, R.; Fernandes, A.; Brites, D.; Freitas, M.; Fernandes, E.; Bronze, M.R.; Figueira, M.E. Protective effects of hydroxytyrosol-supplemented refined olive oil in animal models of acute inflammation and rheumatoid arthritis. J. Nutr. Biochem. 2015, 26, 360-368. [CrossRef] [PubMed]
206. Schaffer, M.; Barbul, A. Lymphocyte function in wound healing and following injury. Br. J. Surg. 1998, 85, 444-460. [CrossRef] [PubMed]
207. Peranteau, W.H.; Zhang, L.; Muvarak, N.; Badillo, A.T.; Radu, A.; Zoltick, P.W.; Liechty, K.W. IL-10 overexpression decreases inflammatory mediators and promotes regenerative healing in an adult model of scar formation. J. Investig. Dermatol. 2008, 128, 1852-1860. [CrossRef] [PubMed]
208. Schwenke, D.C. Aging, menopause, and free radicals. Semin. Reprod. Endocrinol. 1998, 16, 281-308. [CrossRef] [PubMed]
209. Fitó, M.; Cladellas, M.; de la Torre, R.; Marti, J.; Munoz, D.; Schroder, H.; Alcantara, M.; Pujadas-Bastardes, M.; Marrugat, J.; Lopez-Sabater, M.C.; et al. Anti-inflammatory effect of virgin olive oil in stable coronary disease patients: A randomized, crossover, controlled trial. Eur. J. Clin. Nutr. 2008, 62, 570-574. [CrossRef] [PubMed]
210. Loued, S.; Berrougui, H.; Componova, P.; Ikhlef, S.; Helal, O.; Khalil, A. Extra-virgin olive oil consumption reduces the age-related decrease in hdl and paraoxonase 1 anti-inflammatory activities. Br. J. Nutr. 2013, 110, 1272-1284. [CrossRef] [PubMed]
211. Pacheco, Y.M.; Bemudez, B.; Lopez, S.; Abia, R.; Villar, J.; Muriana, F.J. Minor compounds of olive oil have postprandial anti-inflammatory effects. Br. J. Nutr. 2007, 98, 260-263. [CrossRef] [PubMed]
212. Camargo, A.; Ruano, J.; Fernandez, J.M.; Parnell, L.D.; Jimenez, A.; Santos-Gonzalez, M.; Marin, C.; Perez-Martinez, P.; Uceda, M.; Lopez-Miranda, J.; et al. Gene expression changes in mononuclear cells in patients with metabolic syndrome after acute intake of phenol-rich virgin olive oil. BMC Genom. 2010, 11, 253. [CrossRef] [PubMed]
213. Konstantinidou, V.; Covas, M.I.; Munoz-Aguayo, D.; Khymenets, O.; de la Torre, R.; Saez, G.; Tormos Mdel, C.; Toledo, E.; Marti, A.; Ruiz-Gutierrez, V.; et al. In vivo nutrigenomic effects of virgin olive oil polyphenols within the frame of the mediterranean diet: A randomized controlled trial. FASEB J. 2010, 24, 2546-2557. [CrossRef] [PubMed]
214. Aiello, A.; Guccione, G.D.; Accardi, G.; Caruso, C. What olive oil for healthy ageing? Maturitas 2015, 80, 117-118. [CrossRef] [PubMed]
215. Perri, E.; Raffaelli, A.; Sindona, G. Quantitation of oleuropein in virgin olive oil by ionspray mass spectrometry-selected reaction monitoring. J. Agric. Food Chem. 1999, 47, 4156-4160. [CrossRef] [PubMed]
216. Brenes, M.; Garcia, A.; Garcia, P.; Rios, J.J.; Garrido, A. Phenolic compounds in spanish olive oils. J. Agric. Food Chem. 1999, 47, 3535-3540. [CrossRef] [PubMed]
217. 1H-NMR. Establishment of a new index for the characterization of extra virgin olive oils. J. Agric. Food Chem. 2012, 60, 11696-11703. [CrossRef] [PubMed]
218. Karkoula, E.; Skantzari, A.; Melliou, E.; Magiatis, P. Quantitative measurement of major secoiridoid derivatives in olive oil using qnmr. Proof of the artificial formation of aldehydic oleuropein and ligstroside aglycon isomers. J. Agric. Food Chem. 2014, 62, 600-607. [CrossRef] [PubMed]