DNA damage: A main determinant of vascular aging

International Journal of Molecular Sciences

Volumn 17, Issue 5, 2016, Pages

  Bautista Niño, Paula K ^a   Portilla Fernandez, Eliana ^a   Vaughan, Douglas E ^b   Danser, A H Jan ^a   Roks, Anton J M ^a  

^a ERASMUS MEDICAL CENTER   (Netherlands)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Aging; Dietary restriction; DNA damage; Endothelium; eNOS; Genomic instability; PAI 1; Phosphodiesterase; Senescence; Vascular

Indexed keywords

CYCLIN DEPENDENT KINASE 2 INHIBITOR; CYCLIN DEPENDENT KINASE INHIBITOR 2A; CYCLIN DEPENDENT KINASE INHIBITOR 2B; HIGH MOBILITY GROUP B1 PROTEIN; PLASMINOGEN ACTIVATOR INHIBITOR 1; RAPAMYCIN; TELOMERIC REPEAT BINDING FACTOR 2;

AGING; AUTOPHAGY; CARDIOVASCULAR RISK; DIET RESTRICTION; DNA DAMAGE; DNA REPAIR; EXCISION REPAIR; GENE MUTATION; GENOMIC INSTABILITY; HUMAN; HYPERBARIC OXYGEN; NONHUMAN; OXIDATIVE STRESS; PROGERIA; REVIEW; SENESCENCE; SINGLE NUCLEOTIDE POLYMORPHISM; TELOMERE SHORTENING; VASCULAR AGING; ANIMAL; CARDIOVASCULAR DISEASE; GENETICS;

AGING; ANIMALS; CARDIOVASCULAR DISEASES; DNA DAMAGE; DNA REPAIR; GENOMIC INSTABILITY; HUMANS;

EID: 84969142177     PISSN: 16616596     EISSN: 14220067     Source Type: Journal    
DOI: 10.3390/ijms17050748     Document Type: Review

References (185)

1. Mozaffarian, D.; Benjamin, E.J.; Go, A.S.; Arnett, D.K.; Blaha, M.J.; Cushman, M.; de Ferranti, S.; Despres, J.-P.; Fullerton, H.J.; Howard, V.J. Heart disease and stroke statistics-2015 update: A report from the american heart association. Circulation 2015, 131, e29. [CrossRef] [PubMed]
2. Hadi, H.A.R.; Carr, C.S.; Al Suwaidi, J. Endothelial dysfunction: Cardiovascular risk factors, therapy, and outcome. Vasc. Health Risk Manag. 2005, 1, 183-198. [PubMed]
3. Cooney, M.T.; Dudina, A.L.; Graham, I.M. Value and limitations of existing scores for the assessment of cardiovascular risk: A review for clinicians. J. Am. Coll. Cardiol. 2009, 54, 1209-1227. [CrossRef] [PubMed]
4. North, B.J.; Sinclair, D.A. The intersection between aging and cardiovascular disease. Circ. Res. 2012, 110, 1097-1108. [CrossRef] [PubMed]
5. Donato, A.J.; Black, A.D.; Jablonski, K.L.; Gano, L.B.; Seals, D.R. Aging is associated with greater nuclear nf_b, reduced i_b_, and increased expression of proinflammatory cytokines in vascular endothelial cells of healthy humans. Aging Cell 2008, 7, 805-812. [CrossRef] [PubMed]
6. Hamilton, C.A.; Brosnan, M.J.; McIntyre, M.; Graham, D.; Dominiczak, A.F. Superoxide excess in hypertension and aging a common cause of endothelial dysfunction. Hypertension 2001, 37, 529-534. [CrossRef] [PubMed]
7. Tousoulis, D.; Kampoli, A.-M.; Tentolouris Nikolaos Papageorgiou, C.; Stefanadis, C. The role of nitric oxide on endothelial function. Curr. Vasc. Pharmacol. 2012, 10, 4-18. [CrossRef] [PubMed]
8. Wu, H.; Roks, A.J. Genomic instability and vascular aging: A focus on nucleotide excision repair. Trends Cardiovasc. Med. 2014, 24, 61-68. [CrossRef] [PubMed]
9. Lopez-Otin, C.; Blasco, M.A.; Partridge, L.; Serrano, M.; Kroemer, G. The hallmarks of aging. Cell 2013, 153, 1194-1217. [CrossRef] [PubMed]
10. Hakem, R. DNA-damage repair; the good, the bad, and the ugly. EMBO J. 2008, 27, 589-605. [CrossRef] [PubMed]
11. Lans, H.; Hoeijmakers, J.H. Cell biology: Ageing nucleus gets out of shape. Nature 2006, 440, 32-34. [CrossRef] [PubMed]
12. Hasty, P.; Campisi, J.; Hoeijmakers, J.; van Steeg, H.; Vijg, J. Aging and genome maintenance: Lessons from the mouse? Science 2003, 299, 1355-1359. [CrossRef] [PubMed]
13. Hoeijmakers, J.H. DNA damage, aging, and cancer. N. Engl. J. Med. 2009, 361, 1475-1485. [CrossRef] [PubMed]
14. Oeseburg, H.; de Boer, R.A.; van Gilst,W.H.; van der Harst, P. Telomere biology in healthy aging and disease. Pflug. Arch. 2010, 459, 259-268. [CrossRef] [PubMed]
15. Helleday, T.; Eshtad, S.; Nik-Zainal, S. Mechanisms underlying mutational signatures in human cancers. Nat. Rev. Genet. 2014, 15, 585-598. [CrossRef] [PubMed]
16. Marteijn, J.A.; Lans, H.; Vermeulen, W.; Hoeijmakers, J.H. Understanding nucleotide excision repair and its roles in cancer and ageing. Nat. Rev. Mol. Cell Biol. 2014, 15, 465-481. [CrossRef] [PubMed]
17. Childs, B.G.; Durik, M.; Baker, D.J.; van Deursen, J.M. Cellular senescence in aging and age-related disease: From mechanisms to therapy. Nat. Med. 2015, 21, 1424-1435. [CrossRef] [PubMed]
18. Baker, D.J.; Childs, B.G.; Durik, M.; Wijers, M.E.; Sieben, C.J.; Zhong, J.; Saltness, R.A.; Jeganathan, K.B.; Verzosa, G.C.; Pezeshki, A.; et al. Naturally occurring p16Ink4a-positive cells shorten healthy lifespan. Nature 2016, 530, 184-189. [CrossRef] [PubMed]
19. Vermeij,W.P.; Hoeijmakers, J.H.; Pothof, J. Genome integrity in aging: Human syndromes, mouse models, and therapeutic options. Annu. Rev. Pharmacol. Toxicol. 2016, 56, 427-445. [CrossRef] [PubMed]
20. Burtner, C.R.; Kennedy, B.K. Progeria syndromes and ageing: What is the connection? Nat. Rev. Mol. Cell Biol. 2010, 11, 567-578. [CrossRef] [PubMed]
21. Epstein, C.J.; Martin, G.M.; Schultz, A.L.; Motulsky, A.G. Werner’s syndrome a review of its symptomatology, natural history, pathologic features, genetics and relationship to the natural aging process. Medicine (Baltimore) 1966, 45, 177-221. [CrossRef] [PubMed]
22. Shen, J.C.; Gray, M.D.; Oshima, J.; Kamath-Loeb, A.S.; Fry, M.; Loeb, L.A. Werner syndrome protein. I. DNA helicase and dna exonuclease reside on the same polypeptide. J. Biol. Chem. 1998, 273, 34139-34144. [CrossRef] [PubMed]
23. Sanz, M.M.; German, J.; Cunniff, C. Bloom’s Syndrome. In GeneReviews 1993, eBook; Pagon, R.A., Adam, M.P., Ardinger, H.H., et al., Eds.; University ofWashington: Seattle, WA, USA, 2016. [PubMed]
24. Merideth, M.A.; Gordon, L.B.; Clauss, S.; Sachdev, V.; Smith, A.C.; Perry, M.B.; Brewer, C.C.; Zalewski, C.; Kim, H.J.; Solomon, B.; et al. Phenotype and course of hutchinson-gilford progeria syndrome. N. Engl. J. Med. 2008, 358, 592-604. [CrossRef] [PubMed]
25. Olive, M.; Harten, I.; Mitchell, R.; Beers, J.K.; Djabali, K.; Cao, K.; Erdos, M.R.; Blair, C.; Funke, B.; Smoot, L.; et al. Cardiovascular pathology in hutchinson-gilford progeria: Correlation with the vascular pathology of aging. Arterioscler. Thromb. Vasc. Biol. 2010, 30, 2301-2309. [CrossRef] [PubMed]
26. Ragnauth, C.D.; Warren, D.T.; Liu, Y.; McNair, R.; Tajsic, T.; Figg, N.; Shroff, R.; Skepper, J.; Shanahan, C.M. Prelamin A acts to accelerate smooth muscle cell senescence and is a novel biomarker of human vascular aging. Circulation 2010, 121, 2200-2210. [CrossRef] [PubMed]
27. Houtsmuller, A.B.; Rademakers, S.; Nigg, A.L.; Hoogstraten, D.; Hoeijmakers, J.H.; Vermeulen, W. Action of DNA repair endonuclease ERCC1/XPF in living cells. Science 1999, 284, 958-961. [CrossRef] [PubMed]
28. Ahmad, A.; Robinson, A.R.; Duensing, A.; van Drunen, E.; Beverloo, H.B.; Weisberg, D.B.; Hasty, P.; Hoeijmakers, J.H.; Niedernhofer, L.J. ERCC1-XPF endonuclease facilitates DNA double-strand break repair. Mol. Cell. Biol. 2008, 28, 5082-5092. [CrossRef] [PubMed]
29. Bergstralh, D.T.; Sekelsky, J. Interstrand crosslink repair: Can XPF-ERCC1 be let off the hook? Trends Genet. 2008, 24, 70-76. [CrossRef] [PubMed]
30. Kashiyama, K.; Nakazawa, Y.; Pilz, D.T.; Guo, C.; Shimada, M.; Sasaki, K.; Fawcett, H.;Wing, J.F.; Lewin, S.O.; Carr, L.; et al. Malfunction of nuclease ERCC1-XPF results in diverse clinical manifestations and causes cockayne syndrome, xeroderma pigmentosum, and fanconi anemia. Am. J. Hum. Genet. 2013, 92, 807-819. [CrossRef] [PubMed]
31. Gregg, S.Q.; Robinson, A.R.; Niedernhofer, L.J. Physiological consequences of defects in ERCC1-XPF DNA repair endonuclease. DNA Repair 2011, 10, 781-791. [CrossRef] [PubMed]
32. Borghini, A.; Cervelli, T.; Galli, A.; Andreassi, M.G. DNA modifications in atherosclerosis: From the past to the future. Atherosclerosis 2013, 230, 202-209. [CrossRef] [PubMed]
33. Borghini, A.; Mercuri, A.; Turchi, S.; Chiesa, M.R.; Piccaluga, E.; Andreassi, M.G. Increased circulating cell-free DNA levels and mtdna fragments in interventional cardiologists occupationally exposed to low levels of ionizing radiation. Environ. Mol. Mutagen. 2015, 56, 293-300. [CrossRef] [PubMed]
34. Andreassi, M.G.; Piccaluga, E.; Gargani, L.; Sabatino, L.; Borghini, A.; Faita, F.; Bruno, R.M.; Padovani, R.; Guagliumi, G.; Picano, E. Subclinical carotid atherosclerosis and early vascular aging from long-term low-dose ionizing radiation exposure: A genetic, telomere, and vascular ultrasound study in cardiac catheterization laboratory staff. JACC Cardiovasc. Interv. 2015, 8, 616-627. [CrossRef] [PubMed]
35. Preston, D.L.; Shimizu, Y.; Pierce, D.A.; Suyama, A.; Mabuchi, K. Studies of mortality of atomic bomb survivors. Report 13: Solid cancer and noncancer disease mortality: 1950-1997. Radiat. Res. 2003, 160, 381-407. [CrossRef] [PubMed]
36. Martinet, W.; Knaapen, M.W.; de Meyer, G.R.; Herman, A.G.; Kockx, M.M. Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation 2002, 106, 927-932. [CrossRef] [PubMed]
37. Botto, N.; Masetti, S.; Petrozzi, L.; Vassalle, C.; Manfredi, S.; Biagini, A.; Andreassi, M.G. Elevated levels of oxidative DNA damage in patients with coronary artery disease. Coron. Artery Dis. 2002, 13, 269-274. [CrossRef] [PubMed]
38. Durik, M.; Kavousi, M.; van der Pluijm, I.; Isaacs, A.; Cheng, C.; Verdonk, K.; Loot, A.E.; Oeseburg, H.; Bhaggoe, U.M.; Leijten, F.; et al. Nucleotide excision DNA repair is associated with age-related vascular dysfunction. Circulation 2012, 126, 468-478. [CrossRef] [PubMed]
39. Verschuren, J.J.; Trompet, S.; Deelen, J.; Stott, D.J.; Sattar, N.; Buckley, B.M.; Ford, I.; Heijmans, B.T.; Guchelaar, H.J.; Houwing-Duistermaat, J.J.; et al. Non-homologous end-joining pathway associated with occurrence of myocardial infarction: Gene set analysis of genome-wide association study data. PLoS ONE 2013, 8, e56262. [CrossRef] [PubMed]
40. Cervelli, T.; Borghini, A.; Galli, A.; Andreassi, M.G. DNA damage and repair in atherosclerosis: Current insights and future perspectives. Int. J. Mol. Sci. 2012, 13, 16929-16944. [CrossRef] [PubMed]
41. Mahmoudi, M.; Gorenne, I.; Mercer, J.; Figg, N.; Littlewood, T.; Bennett, M. Statins use a novel nijmegen breakage syndrome-1-dependent pathway to accelerateDNArepair in vascular smooth muscle cells. Circ. Res. 2008, 103, 717-725. [CrossRef] [PubMed]
42. Mahmoudi, M.; Mercer, J.; Bennett, M. DNA damage and repair in atherosclerosis. Cardiovasc. Res. 2006, 71, 259-268. [CrossRef] [PubMed]
43. O’Sullivan, R.J.; Karlseder, J. Telomeres: Protecting chromosomes against genome instability. Nat. Rev. Mol. Cell Biol. 2010, 11, 171-181. [CrossRef] [PubMed]
44. De Lange, T. Telomere-related genome instability in cancer. In Cold Spring Harbor Symposia on Quantitative Biology; Cold Spring Harbor Laboratory Press: New York, NY, USA, 2005; Volume 70, pp. 197-204.
45. Deng, Y.; Chang, S. Role of telomeres and telomerase in genomic instability, senescence and cancer. Lab. Investig. 2007, 87, 1071-1076. [CrossRef] [PubMed]
46. Liu, J.-P. Studies of the molecular mechanisms in the regulation of telomerase activity. FASEB J. 1999, 13, 2091-2104. [PubMed]
47. Polanská, E.; Dobšáková, Z.; Dvŏráčková, M.; Fajkus, J.; Štros, M. HMGB1 gene knockout in mouse embryonic fibroblasts results in reduced telomerase activity and telomere dysfunction. Chromosoma 2012, 121, 419-431. [CrossRef] [PubMed]
48. Butt, H.; Atturu, G.; London, N.; Sayers, R.; Bown, M. Telomere length dynamics in vascular disease: A review. Eur. J. Vasc. Endovasc. Surg. 2010, 40, 17-26. [CrossRef] [PubMed]
49. Atturu, G.; Brouilette, S.; Samani, N.; London, N.; Sayers, R.; Bown, M. Short leukocyte telomere length is associated with abdominal aortic aneurysm (AAA). Eur. J. Vasc. Endovasc. Surg. 2010, 39, 559-564. [CrossRef] [PubMed]
50. Ogami, M.; Ikura, Y.; Ohsawa, M.; Matsuo, T.; Kayo, S.; Yoshimi, N.; Hai, E.; Shirai, N.; Ehara, S.; Komatsu, R.; et al. Telomere shortening in human coronary artery diseases. Arterioscler. Thromb. Vasc. Biol. 2004, 24, 546-550. [CrossRef] [PubMed]
51. Samani, N.J.; Boultby, R.; Butler, R.; Thompson, J.R.; Goodall, A.H. Telomere shortening in atherosclerosis. Lancet 2001, 358, 472-473. [CrossRef]
52. Valdes, A.M.; Andrew, T.; Gardner, J.P.; Kimura, M.; Oelsner, E.; Cherkas, L.F.; Aviv, A.; Spector, T.D. Obesity, cigarette smoking, and telomere length in women. Lancet 2005, 366, 662-664. [CrossRef]
53. Fitzpatrick, A.L.; Kronmal, R.A.; Gardner, J.P.; Psaty, B.M.; Jenny, N.S.; Tracy, R.P.;Walston, J.; Kimura, M.; Aviv, A. Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. Am. J. Epidemiol. 2007, 165, 14-21. [CrossRef] [PubMed]
54. Jeanclos, E.; Krolewski, A.; Skurnick, J.; Kimura, M.; Aviv, H.; Warram, J.H.; Aviv, A. Shortened telomere length in white blood cells of patients with iddm. Diabetes 1998, 47, 482-486. [CrossRef] [PubMed]
55. Demissie, S.; Levy, D.; Benjamin, E.J.; Cupples, L.A.; Gardner, J.P.; Herbert, A.; Kimura, M.; Larson, M.G.; Meigs, J.B.; Keaney, J.F.; et al. Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the framingham heart study. Aging Cell 2006, 5, 325-330. [CrossRef] [PubMed]
56. Vasan, R.S.; Demissie, S.; Kimura, M.; Cupples, L.A.; Rifai, N.; White, C.; Wang, T.J.; Gardner, J.P.; Cao, X.; Benjamin, E.J.; et al. Association of leukocyte telomere length with circulating biomarkers of the renin-angiotensin-aldosterone system: The framingham heart study. Circulation 2008, 117, 1138-1144. [CrossRef] [PubMed]
57. Strazhesko, I.; Tkacheva, O.; Boytsov, S.; Akasheva, D.; Dudinskaya, E.; Vygodin, V.; Skvortsov, D.; Nilsson, P. Association of insulin resistance, arterial stiffness and telomere length in adults free of cardiovascular diseases. PLoS ONE 2015, 10, e0136676. [CrossRef] [PubMed]
58. Satoh, M.; Ishikawa, Y.; Takahashi, Y.; Itoh, T.; Minami, Y.; Nakamura, M. Association between oxidative DNA damage and telomere shortening in circulating endothelial progenitor cells obtained from metabolic syndrome patients with coronary artery disease. Atherosclerosis 2008, 198, 347-353. [CrossRef] [PubMed]
59. Brouilette, S.W.; Moore, J.S.; McMahon, A.D.; Thompson, J.R.; Ford, I.; Shepherd, J.; Packard, C.J.; Samani, N.J. West of Scotland Coronary Prevention Study Group. Telomere length, risk of coronary heart disease, and statin treatment in the west of scotland primary prevention study: A nested case-control study. Lancet 2007, 369, 107-114. [CrossRef]
60. 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]
61. Mather, K.A.; Jorm, A.F.; Parslow, R.A.; Christensen, H. Is telomere length a biomarker of aging? A review. J. Gerontol. A Biol. Sci. Med. Sci. 2011, 66, 202-213. [CrossRef] [PubMed]
62. Tchkonia, T.; Zhu, Y.; van Deursen, J.; Campisi, J.; Kirkland, J.L. Cellular senescence and the senescent secretory phenotype: Therapeutic opportunities. J. Clin. Investig. 2013, 123, 966-972. [CrossRef] [PubMed]
63. Kortlever, R.M.; Higgins, P.J.; Bernards, R. Plasminogen activator inhibitor-1 is a critical downstream target of p53 in the induction of replicative senescence. Nat. Cell Biol. 2006, 8, 877-884. [CrossRef] [PubMed]
64. Serrano, M.; Lin, A.W.; McCurrach, M.E.; Beach, D.; Lowe, S.W. Oncogenic ras provokes premature cell senescence associated with accumulation of p53 and p16INK4a. Cell 1997, 88, 593-602. [CrossRef]
65. Takeshita, K.; Yamamoto, K.; Ito, M.; Kondo, T.; Matsushita, T.; Hirai, M.; Kojima, T.; Nishimura, M.; Nabeshima, Y.; Loskutoff, D.J.; et al. Increased expression of plasminogen activator inhibitor-1 with fibrin deposition in a murine model of aging, "klotho" mouse. Semin. Thromb. Hemost. 2002, 28, 545-554. [CrossRef] [PubMed]
66. Aillaud, M.F.; Pignol, F.; Alessi, M.C.; Harle, J.R.; Escande, M.; Mongin, M.; Juhan-Vague, I. Increase in plasma concentration of plasminogen activator inhibitor, fibrinogen, von willebrand factor, factor VIII: C and in erythrocyte sedimentation rate with age. Thromb. Haemost. 1986, 55, 330-332. [PubMed]
67. Eren, M.; Boe, A.E.; Murphy, S.B.; Place, A.T.; Nagpal, V.; Morales-Nebreda, L.; Urich, D.; Quaggin, S.E.; Budinger, G.R.; Mutlu, G.M.; et al. PAI-1-regulated extracellular proteolysis governs senescence and survival in klotho mice. Proc. Natl. Acad. Sci. USA 2014, 111, 7090-7095. [CrossRef] [PubMed]
68. Boe, A.E.; Eren, M.; Murphy, S.B.; Kamide, C.E.; Ichimura, A.; Terry, D.; McAnally, D.; Smith, L.H.; Miyata, T.; Vaughan, D.E. Plasminogen activator inhibitor-1 antagonist TM5441 attenuates N!-nitro-L-arginine methyl ester-induced hypertension and vascular senescence. Circulation 2013, 128, 2318-2324. [CrossRef] [PubMed]
69. Tatar, M.; Bartke, A.; Antebi, A. The endocrine regulation of aging by insulin-like signals. Science 2003, 299, 1346-1351. [CrossRef] [PubMed]
70. Festa, A.; D’Agostino, R., Jr.; Tracy, R.P.; Haffner, S.M. Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: The insulin resistance atherosclerosis study. Diabetes 2002, 51, 1131-1137. [CrossRef] [PubMed]
71. Rosito, G.A.; D’Agostino, R.B.; Massaro, J.; Lipinska, I.; Mittleman, M.A.; Sutherland, P.; Wilson, P.W.; Levy, D.; Muller, J.E.; Tofler, G.H. Association between obesity and a prothrombotic state: The framingham offspring study. Thromb. Haemost. 2004, 91, 683-689. [CrossRef] [PubMed]
72. Olholm, J.; Paulsen, S.K.; Cullberg, K.B.; Richelsen, B.; Pedersen, S.B. Anti-inflammatory effect of resveratrol on adipokine expression and secretion in human adipose tissue explants. Int. J. Obes. (Lond.) 2010, 34, 1546-1553. [CrossRef] [PubMed]
73. Nagi, D.K.; Yudkin, J.S. Effects of metformin on insulin resistance, risk factors for cardiovascular disease, and plasminogen activator inhibitor in niddm subjects. A study of two ethnic groups. Diabetes Care 1993, 16, 621-629. [CrossRef] [PubMed]
74. Colman, R.J.; Beasley, T.M.; Kemnitz, J.W.; Johnson, S.C.;Weindruch, R.; Anderson, R.M. Caloric restriction reduces age-related and all-cause mortality in rhesus monkeys. Nat. Commun. 2014, 5, 3557. [CrossRef] [PubMed]
75. Velthuis-teWierik, E.J.; Meijer, P.; Kluft, C.; van den Berg, H. Beneficial effect of a moderately energy-restricted diet on fibrinolytic factors in non-obese men. Metabolism 1995, 44, 1548-1552. [CrossRef]
76. Nilsson, L.; Banfi, C.; Diczfalusy, U.; Tremoli, E.; Hamsten, A.; Eriksson, P. Unsaturated fatty acids increase plasminogen activator inhibitor-1 expression in endothelial cells. Arterioscler. Thromb. Vasc. Biol. 1998, 18, 1679-1685. [CrossRef] [PubMed]
77. Alessi, M.C.; Juhan-Vague, I.; Kooistra, T.; Declerck, P.J.; Collen, D. Insulin stimulates the synthesis of plasminogen activator inhibitor 1 by the human hepatocellular cell line Hep G2. Thromb. Haemost. 1988, 60, 491-494. [PubMed]
78. Chen, Y.Q.; Su, M.; Walia, R.R.; Hao, Q.; Covington, J.W.; Vaughan, D.E. Sp1 sites mediate activation of the plasminogen activator inhibitor-1 promoter by glucose in vascular smooth muscle cells. J. Biol. Chem. 1998, 273, 8225-8231. [CrossRef] [PubMed]
79. Jeck, W.R.; Siebold, A.P.; Sharpless, N.E. Review: A meta-analysis of gwas and age-associated diseases. Aging Cell 2012, 11, 727-731. [CrossRef] [PubMed]
80. Rodriguez-Menocal, L.; Pham, S.M.; Mateu, D.; St-Pierre, M.; Wei, Y.; Pestana, I.; Aitouche, A.; Vazquez-Padron, R.I. Aging increases p16INK4a expression in vascular smooth-muscle cells. Biosci. Rep. 2010, 30, 11-18. [CrossRef] [PubMed]
81. Motterle, A.; Pu, X.; Wood, H.; Xiao, Q.; Gor, S.; Ng, F.L.; Chan, K.; Cross, F.; Shohreh, B.; Poston, R.N. Functional analyses of coronary artery disease associated variation on chromosome 9p21 in vascular smooth muscle cells. Hum. Mol. Genet. 2012, 21, 4021-4029. [CrossRef] [PubMed]
82. Kim, W.Y.; Sharpless, N.E. The regulation of INK4/ARF in cancer and aging. Cell 2006, 127, 265-275. [CrossRef] [PubMed]
83. Krishnamurthy, J.; Torrice, C.; Ramsey, M.R.; Kovalev, G.I.; Al-Regaiey, K.; Su, L.; Sharpless, N.E. Ink4a/Arf expression is a biomarker of aging. J. Clin. Investig. 2004, 114, 1299-1307. [CrossRef] [PubMed]
84. Sharpless, N.E.; Sherr, C.J. Forging a signature of in vivo senescence. Nat. Rev. Cancer 2015, 15, 397-408. [CrossRef] [PubMed]
85. Perez-Rivero, G.; Ruiz-Torres, M.P.; Rivas-Elena, J.V.; Jerkic, M.; Diez-Marques, M.L.; Lopez-Novoa, J.M.; Blasco, M.A.; Rodriguez-Puyol, D. Mice deficient in telomerase activity develop hypertension because of an excess of endothelin production. Circulation 2006, 114, 309-317. [CrossRef] [PubMed]
86. Massip, L.; Garand, C.; Turaga, R.V.; Deschenes, F.; Thorin, E.; Lebel, M. Increased insulin, triglycerides, reactive oxygen species, and cardiac fibrosis in mice with a mutation in the helicase domain of the werner syndrome gene homologue. Exp. Gerontol. 2006, 41, 157-168. [CrossRef] [PubMed]
87. Chang, S.; Multani, A.S.; Cabrera, N.G.; Naylor, M.L.; Laud, P.; Lombard, D.; Pathak, S.; Guarente, L.; DePinho, R.A. Essential role of limiting telomeres in the pathogenesis of Werner syndrome. Nat. Genet. 2004, 36, 877-882. [CrossRef] [PubMed]
88. Varga, R.; Eriksson, M.; Erdos, M.R.; Olive, M.; Harten, I.; Kolodgie, F.; Capell, B.C.; Cheng, J.; Faddah, D.; Perkins, S.; et al. Progressive vascular smooth muscle cell defects in a mouse model of hutchinson-gilford progeria syndrome. Proc. Natl. Acad. Sci. USA 2006, 103, 3250-3255. [CrossRef] [PubMed]
89. Weeda, G.; Donker, I.; de Wit, J.; Morreau, H.; Janssens, R.; Vissers, C.J.; Nigg, A.; van Steeg, H.; Bootsma, D.; Hoeijmakers, J.H. Disruption of mouse ercc1 results in a novel repair syndrome with growth failure, nuclear abnormalities and senescence. Curr. Biol. 1997, 7, 427-439. [CrossRef]
90. Celermajer, D.S.; Sorensen, K.E.; Spiegelhalter, D.J.; Georgakopoulos, D.; Robinson, J.; Deanfield, J.E. Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. J. Am. Coll. Cardiol. 1994, 24, 471-476. [CrossRef]
91. Kuo, L.; Chilian,W.M.; Davis, M.J. Coronary arteriolar myogenic response is independent of endothelium. Circ. Res. 1990, 66, 860-866. [CrossRef] [PubMed]
92. Kuo, L.; Davis, M.J.; Chilian, W.M. Endothelium-dependent, flow-induced dilation of isolated coronary arterioles. Am. J. Physiol. 1990, 259, H1063-H1070. [PubMed]
93. Gerhard, M.; Roddy, M.A.; Creager, S.J.; Creager, M.A. Aging progressively impairs endothelium-dependent vasodilation in forearm resistance vessels of humans. Hypertension 1996, 27, 849-853. [CrossRef] [PubMed]
94. Broughton, B.C.; Steingrimsdottir, H.;Weber, C.A.; Lehmann, A.R. Mutations in the xeroderma pigmentosum group d DNA repair/transcription gene in patients with trichothiodystrophy. Nat. Genet. 1994, 7, 189-194. [CrossRef] [PubMed]
95. Mercer, J.R.; Cheng, K.K.; Figg, N.; Gorenne, I.; Mahmoudi, M.; Griffin, J.; Vidal-Puig, A.; Logan, A.; Murphy, M.P.; Bennett, M. DNA damage links mitochondrial dysfunction to atherosclerosis and the metabolic syndrome. Circ. Res. 2010, 107, 1021-1031. [CrossRef] [PubMed]
96. Trifunovic, A.; Wredenberg, A.; Falkenberg, M.; Spelbrink, J.N.; Rovio, A.T.; Bruder, C.E.; Bohlooly, Y.M.; Gidlof, S.; Oldfors, A.; Wibom, R.; et al. Premature ageing in mice expressing defective mitochondrial DNA polymerase. Nature 2004, 429, 417-423. [CrossRef] [PubMed]
97. Yu, E.; Calvert, P.A.; Mercer, J.R.; Harrison, J.; Baker, L.; Figg, N.L.; Kumar, S.; Wang, J.C.; Hurst, L.A.; Obaid, D.R.; et al. Mitochondrial DNA damage can promote atherosclerosis independently of reactive oxygen species through effects on smooth muscle cells and monocytes and correlates with higher-risk plaques in humans. Circulation 2013, 128, 702-712. [CrossRef] [PubMed]
98. Dai, D.F.; Rabinovitch, P.S.; Ungvari, Z. Mitochondria and cardiovascular aging. Circ. Res. 2012, 110, 1109-1124. [CrossRef] [PubMed]
99. Chan, G.K.; Jablonski, S.A.; Sudakin, V.; Hittle, J.C.; Yen, T.J. Human BUBR1 is a mitotic checkpoint kinase that monitors cenp-E functions at kinetochores and binds the cyclosome/APC. J. Cell Biol. 1999, 146, 941-954. [CrossRef] [PubMed]
100. Matsumoto, T.; Baker, D.J.; d’Uscio, L.V.; Mozammel, G.; Katusic, Z.S.; van Deursen, J.M. Aging-associated vascular phenotype in mutant mice with low levels of BubR1. Stroke 2007, 38, 1050-1056. [CrossRef] [PubMed]
101. Baker, D.J.; Jeganathan, K.B.; Cameron, J.D.; Thompson, M.; Juneja, S.; Kopecka, A.; Kumar, R.; Jenkins, R.B.; de Groen, P.C.; Roche, P.; et al. BubR1 insufficiency causes early onset of aging-associated phenotypes and infertility in mice. Nat. Genet. 2004, 36, 744-749. [CrossRef] [PubMed]
102. Baker, D.J.; Wijshake, T.; Tchkonia, T.; LeBrasseur, N.K.; Childs, B.G.; van de Sluis, B.; Kirkland, J.L.; van Deursen, J.M. Clearance of p16Ink4a-positive senescent cells delays ageing-associated disorders. Nature 2011, 479, 232-236. [CrossRef] [PubMed]
103. Zhao, Y.; Vanhoutte, P.M.; Leung, S.W.S. Vascular nitric oxide: Beyond enos. J. Pharmacol. Sci. 2015, 129, 83-94. [CrossRef] [PubMed]
104. Lüscher, T.F.; Barton, M. Biology of the endothelium. Clin. Cardiol. Suppl. 1997, 20, 3-10.
105. Yang, Y.M.; Huang, A.; Kaley, G.; Sun, D. Enos uncoupling and endothelial dysfunction in aged vessels. Am. J. Physiol. 2009, 297, H1829-H1836. [CrossRef] [PubMed]
106. Moncada, S.; Palmer, R.M.L.; Higgs, E.A. Nitric oxide: Physiology, pathophysiology, and pharmacology. Pharmacol. Rev. 1991, 43, 109-142. [PubMed]
107. Rudic, R.D.; Shesely, E.G.; Maeda, N.; Smithies, O.; Segal, S.S.; Sessa,W.C. Direct evidence for the importance of endothelium-derived nitric oxide in vascular remodeling. J. Clin. Investig. 1998, 101, 731-736. [CrossRef]
108. Huang, P.L.; Huang, Z.; Mashimo, H.; Bloch, K.D.; Moskowitz, M.A.; Bevan, J.A.; Fishman, M.C. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature 1995, 377, 239-242.
109. Murohara, T.; Asahara, T.; Silver, M.; Bauters, C.; Masuda, H.; Kalka, C.; Kearney, M.; Chen, D.; Symes, J.F.; Fishman, M.C. Nitric oxide synthase modulates angiogenesis in response to tissue ischemia. J. Clin. Investig. 1998, 101, 2567.
110. Freedman, J.E.; Sauter, R.; Battinelli, E.M.; Ault, K.; Knowles, C.; Huang, P.L.; Loscalzo, J. Deficient platelet-derived nitric oxide and enhanced hemostasis in mice lacking the NOSIII gene. Circ. Res. 1999, 84, 1416-1421.
111. Tai, S.C.; Robb, G.B.; Marsden, P.A. Endothelial nitric oxide synthase a new paradigm for gene regulation in the injured blood vessel. Arterioscler. Thromb. Vasc. Biol. 2004, 24, 405-412.
112. Förstermann, U.; Münzel, T. Endothelial nitric oxide synthase in vascular disease from marvel to menace. Circulation 2006, 113, 1708-1714.
113. Bautista Nino, P.K.; Durik, M.; Danser, A.H.; de Vries, R.; Musterd-Bhaggoe, U.M.; Meima, M.E.; Kavousi, M.; Ghanbari, M.; Hoeijmakers, J.H.; O’Donnell, C.J.; et al. Phosphodiesterase 1 regulation is a key mechanism in vascular aging. Clin. Sci. (Lond.) 2015, 129, 1061-1075.
114. Yan, C. Cyclic nucleotide phosphodiesterase 1 and vascular aging. Clin. Sci. (Lond.) 2015, 129, 1077-1081.
115. Rybalkin, S.D.; Rybalkina, I.; Beavo, J.A.; Bornfeldt, K.E. Cyclic nucleotide phosphodiesterase 1C promotes human arterial smooth muscle cell proliferation. Circ. Res. 2002, 90, 151-157.
116. Nguyen, T.; Nioi, P.; Pickett, C.B. The Nrf2-antioxidant response element signaling pathway and its activation by oxidative stress. J. Biol. Chem. 2009, 284, 13291-13295.
117. He, X.; Kan, H.; Cai, L.; Ma, Q. Nrf2 is critical in defense against high glucose-induced oxidative damage in cardiomyocytes. J. Mol. Cell. Cardiol. 2009, 46, 47-58.
118. Warabi, E.; Takabe, W.; Minami, T.; Inoue, K.; Itoh, K.; Yamamoto, M.; Ishii, T.; Kodama, T.; Noguchi, N. Shear stress stabilizes NF-E2-related factor 2 and induces antioxidant genes in endothelial cells: Role of reactive oxygen/nitrogen species. Free Radic. Biol. Med. 2007, 42, 260-269.
119. Mylroie, H.; Dumont, O.; Bauer, A.; Thornton, C.C.; Mackey, J.; Calay, D.; Hamdulay, S.S.; Choo, J.R.; Boyle, J.J.; Samarel, A.M.; et al. PKC"-CREB-Nrf2 signalling induces HO-1 in the vascular endothelium and enhances resistance to inflammation and apoptosis. Cardiovasc. Res. 2015, 106, 509-519.
120. Ungvari, Z.; Bailey-Downs, L.; Sosnowska, D.; Gautam, T.; Koncz, P.; Losonczy, G.; Ballabh, P.; de Cabo, R.; Sonntag, W.E.; Csiszar, A. Vascular oxidative stress in aging: A homeostatic failure due to dysregulation of NRF2-mediated antioxidant response. Am. J. Physiol. Heart Circ. Physiol. 2011, 301, H363-H372.
121. Kapeta, S.; Chondrogianni, N.; Gonos, E.S. Nuclear erythroid factor 2-mediated proteasome activation delays senescence in human fibroblasts. J. Biol. Chem. 2010, 285, 8171-8184.
122. Jódar, L.; Mercken, E.M.; Ariza, J.; Younts, C.; González-Reyes, J.A.; Alcaín, F.J.; Burón, I.; de Cabo, R.; Villalba, J.M. Genetic deletion of Nrf2 promotes immortalization and decreases life span of murine embryonic fibroblasts. J. Gerontol. A Biol. Sci. Med. Sci. 2011, 66, 247-256.
123. Zhou, X.; Zhao, L.; Mao, J.; Huang, J.; Chen, J. Antioxidant effects of hydrogen sulfide on left ventricular remodeling in smoking rats are mediated via PI3K/Akt-dependent activation of Nrf2. Toxicol. Sci. 2015, 144, 197-203.
124. Sussan, T.E.; Rangasamy, T.; Blake, D.J.; Malhotra, D.; El-Haddad, H.; Bedja, D.; Yates, M.S.; Kombairaju, P.; Yamamoto, M.; Liby, K.T.; et al. Targeting Nrf2 with the triterpenoid CDDO-imidazolide attenuates cigarette smoke-induced emphysema and cardiac dysfunction in mice. Proc. Natl. Acad. Sci. USA 2009, 106, 250-255.
125. He, X.; Ma, Q. Disruption of Nrf2 synergizes with high glucose to cause heightened myocardial oxidative stress and severe cardiomyopathy in diabetic mice. J. Diabetes Metab. 2012, (Suppl. S7), [CrossRef]
126. Liao, C.-Y.; Kennedy, B.K. SIRT6, oxidative stress, and aging. Cell Res. 2016, 26, 143-144.
127. Barnhoorn, S.; Uittenboogaard, L.M.; Jaarsma, D.; Vermeij, W.P.; Tresini, M.; Weymaere, M.; Menoni, H.; Brandt, R.M.; deWaard, M.C.; Botter, S.M. Cell-autonomous progeroid changes in conditional mouse models for repair endonuclease xpg deficiency. PLoS Genet. 2014, 10, e1004686.
128. Heiss, E.H.; Schachner, D.; Werner, E.R.; Dirsch, V.M. Active NF-E2-related factor (Nrf2) contributes to keep endothelial NO synthase (eNOS) in the coupled state role of reactive oxygen species (ROS), eNOS, and heme oxygenase (Ho-1) levels. J. Biol. Chem. 2009, 284, 31579-31586.
129. Lawless, C.;Wang, C.; Jurk, D.; Merz, A.; von Zglinicki, T.; Passos, J.F. Quantitative assessment of markers for cell senescence. Exp. Gerontol. 2010, 45, 772-778.
130. Prasher, J.M.; Lalai, A.S.; Heijmans-Antonissen, C.; Ploemacher, R.E.; Hoeijmakers, J.H.; Touw, I.P.; Niedernhofer, L.J. Reduced hematopoietic reserves in DNA interstrand crosslink repair-deficient Ercc1_/_ mice. EMBO J. 2005, 24, 861-871.
131. Durik, M.; Seva Pessoa, B.; Roks, A.J. The renin-angiotensin system, bone marrow and progenitor cells. Clin. Sci. 2012, 123, 205-223.
132. Gelino, S.; Hansen, M. Autophagy-An emerging anti-aging mechanism. J. Clin. Exp. Pathol. 2012, (Suppl. S4). [PubMed] [CrossRef]
133. Levine, B.; Kroemer, G. Autophagy in the pathogenesis of disease. Cell 2008, 132, 27-42.
134. Ward,W.F. The relentless effects of the aging process on protein turnover. Biogerontology 2000, 1, 195-199.
135. Bergamini, E.; Cavallini, G.; Donati, A.; Gori, Z. The role of macroautophagy in the ageing process, anti-ageing intervention and age-associated diseases. Int. J. Biochem. Cell Biol. 2004, 36, 2392-2404.
136. Grootaert, M.O.; da Costa Martins, P.A.; Bitsch, N.; Pintelon, I.; de Meyer, G.R.; Martinet, W.; Schrijvers, D.M. Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes neointima formation and atherogenesis. Autophagy 2015, 11, 2014-2032.
137. Zhang, Y.; Bokov, A.; Gelfond, J.; Soto, V.; Ikeno, Y.; Hubbard, G.; Diaz, V.; Sloane, L.; Maslin, K.; Treaster, S. Rapamycin extends life and health in C57BL/6 mice. J. Gerontol. A Biol. Sci. Med. Sci. 2014, 69, 119-130.
138. Adelman, S.J. Sirolimus and its analogs and its effects on vascular diseases. Curr. Pharm. Des. 2010, 16, 4002-4011.
139. Hudes, G.; Carducci, M.; Tomczak, P.; Dutcher, J.; Figlin, R.; Kapoor, A.; Staroslawska, E.; Sosman, J.; McDermott, D.; Bodrogi, I. Temsirolimus, interferon alfa, or both for advanced renal-cell carcinoma. N. Engl. J. Med. 2007, 356, 2271-2281.
140. Martinet, W.; de Loof, H.; de Meyer, G.R. Mtor inhibition: A promising strategy for stabilization of atherosclerotic plaques. Atherosclerosis 2014, 233, 601-607.
141. Reihl, K.D.; Seals, D.R.; Henson, G.D.; LaRocca, T.J.; Magerko, K.; Bosshardt, G.C.; Lesniewski, L.A.; Donato, A.J. Dietary rapamycin selectively improves arterial function in old mice. FASEB J. 2013, 27, 1194-1117.
142. Donato, A.J.; Morgan, R.G.; Walker, A.E.; Lesniewski, L.A. Cellular and molecular biology of aging endothelial cells. J. Mol. Cell. Cardiol. 2015, 89, 122-135.
143. Marino, G.; Ugalde, A.P.; Salvador-Montoliu, N.; Varela, I.; Quiros, P.M.; Cadinanos, J.; van der Pluijm, I.; Freije, J.M.; Lopez-Otin, C. Premature aging in mice activates a systemic metabolic response involving autophagy induction. Hum. Mol. Genet. 2008, 17, 2196-2211.
144. Reineke, D.C.; Müller-Schweinitzer, E.;Winkler, B.; Kunz, D.; Konerding, M.A.; Grussenmeyer, T.; Carrel, T.P.; Eckstein, F.S.; Grapow, M.T.R. Rapamycin impairs endothelial cell function in human internal thoracic arteries. Eur. J. Med. Res. 2015, 20, 1-8.
145. Trapp, A.; Weis, M. The impact of immunosuppression on endothelial function. J. Cardiovasc. Pharmacol. 2005, 45, 81-87.
146. Mischie, A.N.; Nazzaro, M.S.; Fiorilli, R.; de Felice, F.; Musto, C.; Confessore, P.; Parma, A.; Boschetti, C.; Violini, R. Head-to-head comparison of sirolimus-eluting stent versus bare metal stent evaluation of the coronary endothelial dysfunction in the same patient presenting with multiple coronary artery lesions: The credential study. Catheter. Cardiovasc. Interv. 2013, 82, E184-E191.
147. Habib, A.; Karmali, V.; Polavarapu, R.; Akahori, H.; Cheng, Q.; Pachura, K.; Kolodgie, F.D.; Finn, A.V. Sirolimus-FKBP12.6 impairs endothelial barrier function through protein kinase C-_ activation and disruption of the p120-vascular endothelial cadherin interaction. Arterioscler. Thromb. Vasc. Biol. 2013, 33, 2425-2431.
148. Jiang, P.; Lan, Y.; Luo, J.; Ren, Y.L.; Liu, D.G.; Pang, J.X.; Liu, J.; Li, J.; Wang, C.; Cai, J.P. Rapamycin promoted thrombosis and platelet adhesion to endothelial cells by inducing membrane remodeling. BMC Cell Biol. 2014, 15, 7.
149. Clever, Y.P.; Cremers, B.; Speck, U.; Dietz, U.; Bohm, M.; Scheller, B. Influence of a paclitaxel coated balloon in combination with a bare metal stent on restenosis and endothelial function: Comparison with a drug eluting stent and a bare metal stent. Catheter. Cardiovasc. Interv. 2014, 84, 323-331.
150. Lehle, K.; Birnbaum, D.E.; Preuner, J.G. Predominant inhibition of interleukin-6 synthesis in patient-specific endothelial cells by mtor inhibitors below a concentration range where cell proliferation is affected and mitotic arrest takes place. Transplant. Proc. 2005, 37, 159-161.
151. Muldowney, J.A., 3rd.; Stringham, J.R.; Levy, S.E.; Gleaves, L.A.; Eren, M.; Piana, R.N.; Vaughan, D.E. Antiproliferative agents alter vascular plasminogen activator inhibitor-1 expression: A potential prothrombotic mechanism of drug-eluting stents. Arterioscler. Thromb. Vasc. Biol. 2007, 27, 400-406.
152. Zhu, Y.; Tchkonia, T.; Pirtskhalava, T.; Gower, A.C.; Ding, H.; Giorgadze, N.; Palmer, A.K.; Ikeno, Y.; Hubbard, G.B.; Lenburg, M. The achilles’ heel of senescent cells: From transcriptome to senolytic drugs. Aging Cell 2015, 14, 644-658.
153. 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.
154. Katewa, S.D.; Kapahi, P. Dietary restriction and aging, 2009. Aging Cell 2010, 9, 105-112.
155. Speakman, J.R.; Mitchell, S.E. Caloric restriction. Mol. Asp. Med. 2011, 32, 159-221.
156. McCay, C.M.; Crowell, M.F.; Maynard, L.A. The effect of retarded growth upon the length of life span and upon the ultimate body size. 1935. Nutrition 1989, 5, 155-171, discussion 172.
157. McCay, C.M. Effect of restricted feeding upon aging and chronic diseases in rats and dogs. Am. J. Public Health Nations Health 1947, 37, 521-528.
158. Mair, W.; Dillin, A. Aging and survival: The genetics of life span extension by dietary restriction. Annu. Rev. Biochem. 2008, 77, 727-754.
159. Kennedy, B.K.; Steffen, K.K.; Kaeberlein, M. Ruminations on dietary restriction and aging. Cell. Mol. Life Sci. 2007, 64, 1323-1328.
160. Fontana, L.; Partridge, L.; Longo, V.D. Extending healthy life span-From yeast to humans. Science 2010, 328, 321-326.
161. Masoro, E.J. Overview of caloric restriction and ageing. Mech. Ageing Dev. 2005, 126, 913-922.
162. Parker, B.; Noakes, M.; Luscombe, N.; Clifton, P. Effect of a high-protein, high-monounsaturated fat weight loss diet on glycemic control and lipid levels in type 2 diabetes. Diabetes Care 2002, 25, 425-430.
163. Rees, K.; Dyakova, M.; Ward, K.; Thorogood, M.; Brunner, E. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst. Rev. 2013, 3, CD002128.
164. Csiszar, A.; Labinskyy, N.; Jimenez, R.; Pinto, J.T.; Ballabh, P.; Losonczy, G.; Pearson, K.J.; de Cabo, R.; Ungvari, Z. Anti-oxidative and anti-inflammatory vasoprotective effects of caloric restriction in aging: Role of circulating factors and SIRT1. Mech. Ageing Dev. 2009, 130, 518-527.
165. Donato, A.J.; Walker, A.E.; Magerko, K.A.; Bramwell, R.C.; Black, A.D.; Henson, G.D.; Lawson, B.R.; Lesniewski, L.A.; Seals, D.R. Life-long caloric restriction reduces oxidative stress and preserves nitric oxide bioavailability and function in arteries of old mice. Aging Cell 2013, 12, 772-783.
166. Colman, R.J.; Anderson, R.M.; Johnson, S.C.; Kastman, E.K.; Kosmatka, K.J.; Beasley, T.M.; Allison, D.B.; Cruzen, C.; Simmons, H.A.; Kemnitz, J.W.; et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science 2009, 325, 201-204.
167. Aissa, A.F.; Gomes, T.D.; Almeida, M.R.; Hernandes, L.C.; Darin, J.D.; Bianchi, M.L.; Antunes, L.M. Methionine concentration in the diet has a tissue-specific effect on chromosomal stability in female mice. Food Chem. Toxicol. 2013, 62, 456-462.
168. Di, L.J.; Byun, J.S.; Wong, M.M.; Wakano, C.; Taylor, T.; Bilke, S.; Baek, S.; Hunter, K.; Yang, H.; Lee, M.; et al. Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer. Nat. Commun. 2013, 4, 1449.
169. Vera, E.; Bernardes de Jesus, B.; Foronda, M.; Flores, J.M.; Blasco, M.A. Telomerase reverse transcriptase synergizes with calorie restriction to increase health span and extend mouse longevity. PLoS ONE 2013, 8, e53760.
170. Shammas, M.A. Telomeres, lifestyle, cancer, and aging. Curr. Opin. Clin. Nutr. Metab. Care 2011, 14, 28-34.
171. Blagosklonny, M.V. Calorie restriction: Decelerating mtor-driven aging from cells to organisms (including humans). Cell Cycle 2010, 9, 683-688.
172. Fok, W.C.; Zhang, Y.; Salmon, A.B.; Bhattacharya, A.; Gunda, R.; Jones, D.; Ward, W.; Fisher, K.; Richardson, A.; Pérez, V.I. Short-term treatment with rapamycin and dietary restriction have overlapping and distinctive effects in young mice. J. Gerontol. A Biol. Sci. Med. Sci. 2013, 68, 108-116.
173. Takimoto, E. Controlling myocyte cgmp: Phosphodiesterase 1 joins the fray. Circ. Res. 2009, 105, 931-933.
174. Lugnier, C. PDE inhibitors: A new approach to treat metabolic syndrome? Curr. Opin. Pharmacol. 2011, 11, 698-706.
175. Editorial. Deal watch: Intra-cellular therapies and takeda to develop PDE1 inhibitors for schizophrenia. Nat. Rev. Drug Discov. 2011, 10, 329.
176. Lukowski, R.; Krieg, T.; Rybalkin, S.D.; Beavo, J.; Hofmann, F. Turning on cGMP-dependent pathways to treat cardiac dysfunctions: Boom, bust, and beyond. Trends Pharmacol. Sci. 2014, 35, 404-413.
177. Brown, K.E.; Dhaun, N.; Goddard, J.; Webb, D.J. Potential therapeutic role of phosphodiesterase type 5 inhibition in hypertension and chronic kidney disease. Hypertension 2014, 63, 5-11.
178. Kemeny, V.; Molnar, S.; Andrejkovics, M.; Makai, A.; Csiba, L. Acute and chronic effects of vinpocetine on cerebral hemodynamics and neuropsychological performance in multi-infarct patients. J. Clin. Pharmacol. 2005, 45, 1048-1054.
179. Cai, Y.; Knight, W.E.; Guo, S.; Li, J.D.; Knight, P.A.; Yan, C. Vinpocetine suppresses pathological vascular remodeling by inhibiting vascular smooth muscle cell proliferation and migration. J. Pharmacol. Exp. Ther. 2012, 343, 479-488.
180. Zhuang, J.; Peng, W.; Li, H.; Lu, Y.; Wang, K.; Fan, F.; Li, S.; Xu, Y. Inhibitory effects of vinpocetine on the progression of atherosclerosis are mediated by Akt/NF-_B dependent mechanisms in apoE_/_ mice. PLoS ONE 2013, 8, e82509.
181. Myung, S.-K.; Ju,W.; Cho, B.; Oh, S.-W.; Park, S.M.; Koo, B.-K.; Park, B.-J. Efficacy of vitamin and antioxidant supplements in prevention of cardiovascular disease: Systematic review and meta-analysis of randomised controlled trials. BMJ 2013, 346, f10.
182. Kornfeld, O.S.; Hwang, S.; Disatnik, M.-H.; Chen, C.-H.; Qvit, N.; Mochly-Rosen, D. Mitochondrial reactive oxygen species at the heart of the matter new therapeutic approaches for cardiovascular diseases. Circ. Res. 2015, 116, 1783-1799.
183. Bruns, D.R.; Drake, J.C.; Biela, L.M.; Peelor Iii, F.F.; Miller, B.F.; Hamilton, K.L.; Cabello-Verrugio, C. Nrf2 signaling and the slowed aging phenotype: Evidence from long-lived models. Oxid. Med. Cell. Longev. 2015, 2015, 732596.
184. Ramprasath, T.; Vasudevan, V.; Sasikumar, S.; Syed Mohamed Puhari, S.; Saso, L.; Sadasivam Selvam, G. Regression of oxidative stress by targeting eNOS and Nrf2/ARE signaling: A guided drug target for cardiovascular diseases. Curr. Top. Med. Chem. 2015, 15, 857-871.
185. Bocci, V.; Valacchi, G. Nrf2 activation as target to implement therapeutic treatments. Front. Chem. 2015, 3, 4.