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Current Medicinal Chemistry

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ISSN (Online): 1875-533X

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Review Article

Inflammatory Molecular Mediators and Pathways Involved in Vascular Aging and Stroke: A Comprehensive Review

Author(s): Amro M. Soliman, Srijit Das* and Pasuk Mahakkanukrauh

Volume 29, Issue 34, 2022

Published on: 01 September, 2021

Page: [5522 - 5542] Pages: 21

DOI: 10.2174/0929867328666210901122359

Price: $65

Abstract

There is an increase in the incidence of cardiovascular diseases with aging and it is one of the leading causes of death worldwide. The main cardiovascular pathologies include atherosclerosis, myocardial infarction, hypertension and stroke. Chronic inflammation is one of the significant contributors to the age-related vascular diseases. Therefore, it is important to understand the molecular mechanisms of the persistent inflammatory conditions occurring in the blood vessels as well as the signaling pathways involved. Herein, we performed an extant search of literature involving PubMed, ISI, WoS and Scopus databases for retrieving all relevant articles with the most recent findings illustrating the potential role of various inflammatory mediators along with their proposed activated pathways in the pathogenesis and progression of vascular aging. We also highlight the major pathways contributing to age-related vascular disorders. The outlined molecular mechanisms, pathways and mediators of vascular aging represent potential drug targets that can be utilized to inhibit and/or slow the pathogenesis and progression of vascular aging.

Keywords: Cardiovascular, inflammation, stroke, atherosclerosis, vascular aging, inflammatory mediators.

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[1]
Ter Horst, R.; Jaeger, M.; Smeekens, S.P.; Oosting, M.; Swertz, M.A.; Li, Y.; Kumar, V.; Diavatopoulos, D.A.; Jansen, A.F.M.; Lemmers, H.; Toenhake-Dijkstra, H.; van Herwaarden, A.E.; Janssen, M.; van der Molen, R.G.; Joosten, I.; Sweep, F.C.G.J.; Smit, J.W.; Netea-Maier, R.T.; Koenders, M.M.J.F.; Xavier, R.J.; van der Meer, J.W.M.; Dinarello, C.A.; Pavelka, N.; Wijmenga, C.; Notebaart, R.A.; Joosten, L.A.B.; Netea, M.G. Host and environmental factors influencing individual human cytokine responses. Cell, 2016, 167(4), 1111-1124.e13.
[http://dx.doi.org/10.1016/j.cell.2016.10.018] [PMID: 27814508]
[2]
Rea, J.N.M.; Carvalho, A.; McNerlan, S.E.; Alexander, H.D.; Rea, I.M. Genes and life-style factors in BELFAST nonagenarians: nature, nurture and narrative. Biogerontology, 2015, 16(5), 587-597.
[http://dx.doi.org/10.1007/s10522-015-9567-y] [PMID: 25773008]
[3]
Liu, Y-Z.; Wang, Y-X.; Jiang, C-L. Inflammation: the common pathway of stress-related diseases. Front. Hum. Neurosci., 2017, 11, 316.
[http://dx.doi.org/10.3389/fnhum.2017.00316] [PMID: 28676747]
[4]
Medzhitov, R. Inflammation 2010: new adventures of an old flame. Cell, 2010, 140(6), 771-776.
[http://dx.doi.org/10.1016/j.cell.2010.03.006] [PMID: 20303867]
[5]
Abe, K.; Hashimoto, Y.; Yatsushiro, S.; Yamamura, S.; Bando, M.; Hiroshima, Y.; Kido, J.; Tanaka, M.; Shinohara, Y.; Ooie, T.; Baba, Y.; Kataoka, M. Simultaneous immunoassay analysis of plasma IL-6 and TNF-α on a microchip. PLoS One, 2013, 8(1), e53620.
[http://dx.doi.org/10.1371/journal.pone.0053620] [PMID: 23326472]
[6]
Battle, A.; Khan, Z.; Wang, S.H.; Mitrano, A.; Ford, M.J.; Pritchard, J.K.; Gilad, Y. Genomic variation. Impact of regulatory variation from RNA to protein. Science, 2015, 347(6222), 664-667.
[http://dx.doi.org/10.1126/science.1260793] [PMID: 25657249]
[7]
Kubiczkova, L.; Sedlarikova, L.; Hajek, R.; Sevcikova, S. TGF-β - an excellent servant but a bad master. J. Transl. Med., 2012, 10, 183.
[http://dx.doi.org/10.1186/1479-5876-10-183] [PMID: 22943793]
[8]
Franceschi, C.; Bonafè, M.; Valensin, S.; Olivieri, F.; De Luca, M.; Ottaviani, E.; De Benedictis, G. Inflamm-aging. An evolutionary perspective on immunosenescence. Ann. N. Y. Acad. Sci., 2000, 908, 244-254.
[http://dx.doi.org/10.1111/j.1749-6632.2000.tb06651.x] [PMID: 10911963]
[9]
Franceschi, C.; Capri, M.; Monti, D.; Giunta, S.; Olivieri, F.; Sevini, F.; Panourgia, M.P.; Invidia, L.; Celani, L.; Scurti, M.; Cevenini, E.; Castellani, G.C.; Salvioli, S. Inflammaging and anti-inflammaging: a systemic perspective on aging and longevity emerged from studies in humans. Mech. Ageing Dev., 2007, 128(1), 92-105.
[http://dx.doi.org/10.1016/j.mad.2006.11.016] [PMID: 17116321]
[10]
Franceschi, C.; Campisi, J. Chronic inflammation (inflammaging) and its potential contribution to age-associated diseases. J. Gerontol. A Biol. Sci. Med. Sci., 2014, 69(Suppl. 1), S4-S9.
[http://dx.doi.org/10.1093/gerona/glu057] [PMID: 24833586]
[11]
Chung, H.Y.; Cesari, M.; Anton, S.; Marzetti, E.; Giovannini, S.; Seo, A.Y.; Carter, C.; Yu, B.P.; Leeuwenburgh, C. Molecular inflammation: underpinnings of aging and age-related diseases. Ageing Res. Rev., 2009, 8(1), 18-30.
[http://dx.doi.org/10.1016/j.arr.2008.07.002] [PMID: 18692159]
[12]
Rea, I.M.; Gibson, D.S.; McGilligan, V.; McNerlan, S.E.; Alexander, H.D.; Ross, O.A. Age and age-related diseases: role of inflammation triggers and cytokines. Front. Immunol., 2018, 9, 586.
[http://dx.doi.org/10.3389/fimmu.2018.00586] [PMID: 29686666]
[13]
Fredman, G.; Hellmann, J.; Proto, J.D.; Kuriakose, G.; Colas, R.A.; Dorweiler, B.; Connolly, E.S.; Solomon, R.; Jones, D.M.; Heyer, E.J.; Spite, M.; Tabas, I. An imbalance between specialized pro-resolving lipid mediators and pro-inflammatory leukotrienes promotes instability of atherosclerotic plaques. Nat. Commun., 2016, 7, 12859.
[http://dx.doi.org/10.1038/ncomms12859] [PMID: 27659679]
[14]
Forsey, R.J.; Thompson, J.M.; Ernerudh, J.; Hurst, T.L.; Strindhall, J.; Johansson, B.; Nilsson, B-O.; Wikby, A. Plasma cytokine profiles in elderly humans. Mech. Ageing Dev., 2003, 124(4), 487-493.
[http://dx.doi.org/10.1016/S0047-6374(03)00025-3] [PMID: 12714257]
[15]
Ferrucci, L.; Harris, T.B.; Guralnik, J.M.; Tracy, R.P.; Corti, M.C.; Cohen, H.J.; Penninx, B.; Pahor, M.; Wallace, R.; Havlik, R.J. Serum IL-6 level and the development of disability in older persons. J. Am. Geriatr. Soc., 1999, 47(6), 639-646.
[http://dx.doi.org/10.1111/j.1532-5415.1999.tb01583.x] [PMID: 10366160]
[16]
Wei, J.; Xu, H.; Davies, J.L.; Hemmings, G.P. Increase of plasma IL-6 concentration with age in healthy subjects. Life Sci., 1992, 51(25), 1953-1956.
[http://dx.doi.org/10.1016/0024-3205(92)90112-3] [PMID: 1453878]
[17]
Fichtlscherer, S.; Rosenberger, G.; Walter, D.H.; Breuer, S.; Dimmeler, S.; Zeiher, A.M. Elevated C-reactive protein levels and impaired endothelial vasoreactivity in patients with coronary artery disease. Circulation, 2000, 102(9), 1000-1006.
[http://dx.doi.org/10.1161/01.CIR.102.9.1000] [PMID: 10961964]
[18]
Lind, L.; Siegbahn, A.; Hulthe, J.; Elmgren, A. C-reactive protein and e-selectin levels are related to vasodilation in resistance, but not conductance arteries in the elderly: the prospective investigation of the Vasculature in Uppsala Seniors (PIVUS) study. Atherosclerosis, 2008, 199(1), 129-137.
[http://dx.doi.org/10.1016/j.atherosclerosis.2007.09.038] [PMID: 17991470]
[19]
Mattace-Raso, F.U.S.; van der Cammen, T.J.M.; van der Meer, I.M.; Schalekamp, M.A.D.H.; Asmar, R.; Hofman, A.; Witteman, J.C.M. C-reactive protein and arterial stiffness in older adults: the Rotterdam Study. Atherosclerosis, 2004, 176(1), 111-116.
[http://dx.doi.org/10.1016/j.atherosclerosis.2004.04.014] [PMID: 15306182]
[20]
Joseph, V.A.; John, K.F.; Martin, L.G.; Michelle, K.J.; Joseph, M.M.; Izabella, L.; Birgitta, L.T.; Shuxia, F.; Ewa, O.; Peter, W.W.F.; Ramachandran, V.S.; Gary, M.F.; Emelia, B.J. Brachial artery vasodilator function and systemic inflammation in the framingham offspring study. Circulation, 2004, 110, 3604-3609.
[21]
Schnabel, R.; Larson, M.G.; Dupuis, J.; Lunetta, K.L.; Lipinska, I.; Meigs, J.B.; Yin, X.; Rong, J.; Vita, J.A.; Newton-Cheh, C.; Levy, D.; Keaney, J.F., Jr; Vasan, R.S.; Mitchell, G.F.; Benjamin, E.J. Relations of inflammatory biomarkers and common genetic variants with arterial stiffness and wave reflection. Hypertension, 2008, 51(6), 1651-1657.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.105668] [PMID: 18426996]
[22]
Tchalla, A.E.; Wellenius, G.A.; Travison, T.G.; Gagnon, M.; Iloputaife, I.; Dantoine, T.; Sorond, F.A.; Lipsitz, L.A. Circulating vascular cell adhesion molecule-1 is associated with cerebral blood flow dysregulation, mobility impairment, and falls in older adults. Hypertension, 2015, 66(2), 340-346.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.115.05180] [PMID: 26056332]
[23]
Walker, A.E.; Seibert, S.M.; Donato, A.J.; Pierce, G.L.; Seals, D.R. Vascular endothelial function is related to white blood cell count and myeloperoxidase among healthy middle-aged and older adults. Hypertension, 2010, 55(2), 363-369.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.145870] [PMID: 20048194]
[24]
Puz, P.; Lasek-Bal, A.; Ziaja, D.; Kazibutowska, Z.; Ziaja, K. Inflammatory markers in patients with internal carotid artery stenosis. Arch. Med. Sci., 2013, 9(2), 254-260.
[http://dx.doi.org/10.5114/aoms.2013.34533] [PMID: 23671435]
[25]
Giacconi, R.; Cipriano, C.; Albanese, F.; Boccoli, G.; Saba, V.; Olivieri, F.; Franceschi, C.; Mocchegiani, E. The -174G/C polymorphism of IL-6 is useful to screen old subjects at risk for atherosclerosis or to reach successful ageing. Exp. Gerontol., 2004, 39(4), 621-628.
[http://dx.doi.org/10.1016/j.exger.2003.12.013] [PMID: 15050298]
[26]
Freitas, W.M.; Quaglia, L.A.; Santos, S.N.; Soares, A.A.S.; Japiassú, A.V.T.; Boaventura, V.; dos Santos Barros, E.; Córdova, C.; Nóbrega, O.T.; Sposito, A.C. Association of systemic inflammatory activity with coronary and carotid atherosclerosis in the very elderly. Atherosclerosis, 2011, 216(1), 212-216.
[http://dx.doi.org/10.1016/j.atherosclerosis.2011.01.040] [PMID: 21316055]
[27]
Machado-Silva, W.; Henriques, A.D.; Souza, G.D.; Gomes, L.; Ferreira, A.P.; Brito, C.J.; Córdova, C.; Moraes, C.F.; Nóbrega, O.T. Serum immune mediators independently associate with atherosclerosis in the left (but not right) carotid territory of older individuals. J. Stroke Cerebrovasc. Dis., 2016, 25(12), 2851-2858.
[http://dx.doi.org/10.1016/j.jstrokecerebrovasdis.2016.07.047] [PMID: 27554076]
[28]
Koh, S.J.; Kim, J.Y.; Hyun, Y.J.; Park, S.H.; Chae, J.S.; Park, S.; Kim, J-S.; Youn, J.C.; Jang, Y.; Lee, J.H. Association of serum RANTES concentrations with established cardiovascular risk markers in middle-aged subjects. Int. J. Cardiol., 2009, 132(1), 102-108.
[http://dx.doi.org/10.1016/j.ijcard.2007.10.038] [PMID: 18190991]
[29]
Rodríguez-Mañas, L.; El-Assar, M.; Vallejo, S.; López-Dóriga, P.; Solís, J.; Petidier, R.; Montes, M.; Nevado, J.; Castro, M.; Gómez-Guerrero, C.; Peiró, C.; Sánchez-Ferrer, C.F. Endothelial dysfunction in aged humans is related with oxidative stress and vascular inflammation. Aging Cell, 2009, 8(3), 226-238.
[http://dx.doi.org/10.1111/j.1474-9726.2009.00466.x] [PMID: 19245678]
[30]
Samuel, M.; Tardif, J-C.; Khairy, P.; Roubille, F.; Waters, D.D.; Grégoire, J.C.; Pinto, F.J.; Maggioni, A.P.; Diaz, R.; Berry, C.; Koenig, W.; Ostadal, P.; Lopez-Sendon, J.; Gamra, H.; Kiwan, G.S.; Dubé, M-P.; Provencher, M.; Orfanos, A.; Blondeau, L.; Kouz, S.; L’Allier, P.L.; Ibrahim, R.; Bouabdallaoui, N.; Mitchell, D.; Guertin, M-C.; Lelorier, J. Cost-effectiveness of low-dose colchicine after myocardial infarction in the colchicine cardiovascular outcomes trial (COLCOT). Eur. Heart J. Qual. Care Clin. Outcomes, 2020, •••, qcaa045.
[http://dx.doi.org/10.1093/ehjqcco/qcaa045]
[31]
Nidorf, S.M.; Fiolet, A.T.L.; Mosterd, A.; Eikelboom, J.W.; Schut, A.; Opstal, T.S.J.; The, S.H.K.; Xu, X-F.; Ireland, M.A.; Lenderink, T.; Latchem, D.; Hoogslag, P.; Jerzewski, A.; Nierop, P.; Whelan, A.; Hendriks, R.; Swart, H.; Schaap, J.; Kuijper, A.F.M.; van Hessen, M.W.J.; Saklani, P.; Tan, I.; Thompson, A.G.; Morton, A.; Judkins, C.; Bax, W.A.; Dirksen, M.; Alings, M.; Hankey, G.J.; Budgeon, C.A.; Tijssen, J.G.P.; Cornel, J.H.; Thompson, P.L. Colchicine in patients with chronic coronary disease. N. Engl. J. Med., 2020, 383(19), 1838-1847.
[http://dx.doi.org/10.1056/NEJMoa2021372] [PMID: 32865380]
[32]
Tong, D.C.; Quinn, S.; Nasis, A.; Hiew, C.; Roberts-Thomson, P.; Adams, H.; Sriamareswaran, R.; Htun, N.M.; Wilson, W.; Stub, D.; van Gaal, W.; Howes, L.; Collins, N.; Yong, A.; Bhindi, R.; Whitbourn, R.; Lee, A.; Hengel, C.; Asrress, K.; Freeman, M.; Amerena, J.; Wilson, A.; Layland, J. Colchicine in patients with acute coronary syndrome: the australian COPS randomized clinical trial. Circulation, 2020, 142(20), 1890-1900.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.120.050771] [PMID: 32862667]
[33]
Ridker, P.M.; Devalaraja, M.; Baeres, F.M.M.; Engelmann, M.D.M.; Hovingh, G.K.; Ivkovic, M.; Lo, L.; Kling, D.; Pergola, P.; Raj, D.; Libby, P.; Davidson, M. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet, 2021, 397(10289), 2060-2069.
[http://dx.doi.org/10.1016/S0140-6736(21)00520-1] [PMID: 34015342]
[34]
Ershler, W.B. Interleukin-6: a cytokine for gerontologists. J. Am. Geriatr. Soc., 1993, 41(2), 176-181.
[http://dx.doi.org/10.1111/j.1532-5415.1993.tb02054.x] [PMID: 8426042]
[35]
Ershler, W.B.; Keller, E.T. Age-associated increased interleukin-6 gene expression, late-life diseases, and frailty. Annu. Rev. Med., 2000, 51, 245-270.
[http://dx.doi.org/10.1146/annurev.med.51.1.245] [PMID: 10774463]
[36]
Weiss, T.W.; Arnesen, H.; Seljeflot, I. Components of the interleukin-6 transsignalling system are associated with the metabolic syndrome, endothelial dysfunction and arterial stiffness. Metabolism, 2013, 62(7), 1008-1013.
[http://dx.doi.org/10.1016/j.metabol.2013.01.019] [PMID: 23428306]
[37]
Puzianowska-Kuźnicka, M.; Owczarz, M.; Wieczorowska-Tobis, K.; Nadrowski, P.; Chudek, J.; Slusarczyk, P.; Skalska, A.; Jonas, M.; Franek, E.; Mossakowska, M. Interleukin-6 and C-reactive protein, successful aging, and mortality: the PolSenior study. Immun. Ageing, 2016, 13, 21.
[http://dx.doi.org/10.1186/s12979-016-0076-x] [PMID: 27274758]
[38]
Van Epps, P.; Oswald, D.; Higgins, P.A.; Hornick, T.R.; Aung, H.; Banks, R.E.; Wilson, B.M.; Burant, C.; Graventstein, S.; Canaday, D.H. Frailty has a stronger association with inflammation than age in older veterans. Immun. Ageing, 2016, 13, 27.
[http://dx.doi.org/10.1186/s12979-016-0082-z] [PMID: 27777599]
[39]
Varadhan, R.; Yao, W.; Matteini, A.; Beamer, B.A.; Xue, Q-L.; Yang, H.; Manwani, B.; Reiner, A.; Jenny, N.; Parekh, N.; Fallin, M.D.; Newman, A.; Bandeen-Roche, K.; Tracy, R.; Ferrucci, L.; Walston, J. Simple biologically informed inflammatory index of two serum cytokines predicts 10 year all-cause mortality in older adults. J. Gerontol. A Biol. Sci. Med. Sci., 2014, 69(2), 165-173.
[http://dx.doi.org/10.1093/gerona/glt023] [PMID: 23689826]
[40]
Hubbard, R.E.; O’Mahony, M.S.; Savva, G.M.; Calver, B.L.; Woodhouse, K.W. Inflammation and frailty measures in older people. J. Cell. Mol. Med., 2009, 13(9B), 3103-3109.
[http://dx.doi.org/10.1111/j.1582-4934.2009.00733.x] [PMID: 19438806]
[41]
Alemán, H.; Esparza, J.; Ramirez, F.A.; Astiazaran, H.; Payette, H. Longitudinal evidence on the association between interleukin-6 and C-reactive protein with the loss of total appendicular skeletal muscle in free-living older men and women. Age Ageing, 2011, 40(4), 469-475.
[http://dx.doi.org/10.1093/ageing/afr040] [PMID: 21565862]
[42]
Ridker, P.M.; Rifai, N.; Stampfer, M.J.; Hennekens, C.H. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation, 2000, 101(15), 1767-1772.
[http://dx.doi.org/10.1161/01.CIR.101.15.1767] [PMID: 10769275]
[43]
Miwa, K.; Okazaki, S.; Sakaguchi, M.; Mochizuki, H.; Kitagawa, K. Interleukin-6, interleukin-6 receptor gene variant, small-vessel disease and incident dementia. Eur. J. Neurol., 2016, 23(3), 656-663.
[http://dx.doi.org/10.1111/ene.12921] [PMID: 26725994]
[44]
Spoto, B.; Mattace-Raso, F.; Sijbrands, E.; Leonardis, D.; Testa, A.; Pisano, A.; Pizzini, P.; Cutrupi, S.; Parlongo, R.M.; D’Arrigo, G.; Tripepi, G.; Mallamaci, F.; Zoccali, C. Association of IL-6 and a functional polymorphism in the IL-6 gene with cardiovascular events in patients with CKD. Clin. J. Am. Soc. Nephrol., 2015, 10(2), 232-240.
[http://dx.doi.org/10.2215/CJN.07000714] [PMID: 25492254]
[45]
Di Bona, D.; Vasto, S.; Capurso, C.; Christiansen, L.; Deiana, L.; Franceschi, C.; Hurme, M.; Mocchegiani, E.; Rea, M.; Lio, D.; Candore, G.; Caruso, C. Effect of interleukin-6 polymorphisms on human longevity: a systematic review and meta-analysis. Ageing Res. Rev., 2009, 8(1), 36-42.
[http://dx.doi.org/10.1016/j.arr.2008.09.001] [PMID: 18930842]
[46]
Soerensen, M.; Dato, S.; Tan, Q.; Thinggaard, M.; Kleindorp, R.; Beekman, M.; Suchiman, H.E.D.; Jacobsen, R.; McGue, M.; Stevnsner, T.; Bohr, V.A.; de Craen, A.J.M.; Westendorp, R.G.J.; Schreiber, S.; Slagboom, P.E.; Nebel, A.; Vaupel, J.W.; Christensen, K.; Christiansen, L. Evidence from case-control and longitudinal studies supports associations of genetic variation in APOE, CETP, and IL6 with human longevity. Age (Dordr.), 2013, 35(2), 487-500.
[http://dx.doi.org/10.1007/s11357-011-9373-7] [PMID: 22234866]
[47]
Swerdlow, D.I.; Holmes, M.V.; Kuchenbaecker, K.B.; Engmann, J.E.L.; Shah, T.; Sofat, R.; Guo, Y.; Chung, C.; Peasey, A.; Pfister, R.; Mooijaart, S.P.; Ireland, H.A.; Leusink, M.; Langenberg, C.; Li, K.W.; Palmen, J.; Howard, P.; Cooper, J.A.; Drenos, F.; Hardy, J.; Nalls, M.A.; Li, Y.R.; Lowe, G.; Stewart, M.; Bielinski, S.J.; Peto, J.; Timpson, N.J.; Gallacher, J.; Dunlop, M.; Houlston, R.; Tomlinson, I.; Tzoulaki, I.; Luan, J.; Boer, J.M.A.; Forouhi, N.G.; Onland-Moret, N.C.; van der Schouw, Y.T.; Schnabel, R.B.; Hubacek, J.A.; Kubinova, R.; Baceviciene, M.; Tamosiunas, A.; Pajak, A.; Topor-Madry, R.; Malyutina, S.; Baldassarre, D.; Sennblad, B.; Tremoli, E.; de Faire, U.; Ferrucci, L.; Bandenelli, S.; Tanaka, T.; Meschia, J.F.; Singleton, A.; Navis, G.; Mateo Leach, I.; Bakker, S.J.L.; Gansevoort, R.T.; Ford, I.; Epstein, S.E.; Burnett, M.S.; Devaney, J.M.; Jukema, J.W.; Westendorp, R.G.J.; Jan de Borst, G.; van der Graaf, Y.; de Jong, P.A.; Mailand-van der Zee, A-H.; Klungel, O.H.; de Boer, A.; Doevendans, P.A.; Stephens, J.W.; Eaton, C.B.; Robinson, J.G.; Manson, J.E.; Fowkes, F.G.; Frayling, T.M.; Price, J.F.; Whincup, P.H.; Morris, R.W.; Lawlor, D.A.; Smith, G.D.; Ben-Shlomo, Y.; Redline, S.; Lange, L.A.; Kumari, M.; Wareham, N.J.; Verschuren, W.M.M.; Benjamin, E.J.; Whittaker, J.C.; Hamsten, A.; Dudbridge, F.; Delaney, J.A.C.; Wong, A.; Kuh, D.; Hardy, R.; Castillo, B.A.; Connolly, J.J.; van der Harst, P.; Brunner, E.J.; Marmot, M.G.; Wassel, C.L.; Humphries, S.E.; Talmud, P.J.; Kivimaki, M.; Asselbergs, F.W.; Voevoda, M.; Bobak, M.; Pikhart, H.; Wilson, J.G.; Hakonarson, H.; Reiner, A.P.; Keating, B.J.; Sattar, N.; Hingorani, A.D.; Casas, J.P. The interleukin-6 receptor as a target for prevention of coronary heart disease: a mendelian randomisation analysis. Lancet, 2012, 379(9822), 1214-1224.
[http://dx.doi.org/10.1016/S0140-6736(12)60110-X] [PMID: 22421340]
[48]
Davies, R.; Choy, E. Clinical experience of IL-6 blockade in rheumatic diseases - implications on IL-6 biology and disease pathogenesis. Semin. Immunol., 2014, 26(1), 97-104.
[http://dx.doi.org/10.1016/j.smim.2013.12.002] [PMID: 24389239]
[49]
Ferrucci, L.; Corsi, A.; Lauretani, F.; Bandinelli, S.; Bartali, B.; Taub, D.D.; Guralnik, J.M.; Longo, D.L. The origins of age-related proinflammatory state. Blood, 2005, 105(6), 2294-2299.
[http://dx.doi.org/10.1182/blood-2004-07-2599] [PMID: 15572589]
[50]
Sims, J.E.; Smith, D.E. The IL-1 family: regulators of immunity. Nat. Rev. Immunol., 2010, 10(2), 89-102.
[http://dx.doi.org/10.1038/nri2691] [PMID: 20081871]
[51]
McNerlan, S.E.; Rea, I.M.; Alexander, H.D. A whole blood method for measurement of intracellular TNF-alpha, IFN-gamma and IL-2 expression in stimulated CD3+ lymphocytes: differences between young and elderly subjects. Exp. Gerontol., 2002, 37(2-3), 227-234.
[http://dx.doi.org/10.1016/S0531-5565(01)00188-7] [PMID: 11772508]
[52]
O’Mahony, L.; Holland, J.; Jackson, J.; Feighery, C.; Hennessy, T.P.; Mealy, K. Quantitative intracellular cytokine measurement: age-related changes in proinflammatory cytokine production. Clin. Exp. Immunol., 1998, 113(2), 213-219.
[http://dx.doi.org/10.1046/j.1365-2249.1998.00641.x] [PMID: 9717970]
[53]
Armstrong, M.E.; Alexander, H.D.; Ritchie, J.L.; McMillan, S.A.; Rea, I.M. Age-related alterations in basal expression and in vitro, tumour necrosis factor alpha mediated, upregulation of CD11b. Gerontology, 2001, 47(4), 180-185.
[http://dx.doi.org/10.1159/000052795] [PMID: 11408721]
[54]
Bruunsgaard, H.; Skinhøj, P.; Pedersen, A.N.; Schroll, M.; Pedersen, B.K. Ageing, tumour necrosis factor-α (TNF-α) and atherosclerosis. Clin. Exp. Immunol., 2000, 121(2), 255-260.
[http://dx.doi.org/10.1046/j.1365-2249.2000.01281.x] [PMID: 10931139]
[55]
Ridker Paul, M. Rifai Nader; Pfeffer Marc; Sacks Frank; Lepage serge; braunwald eugene. elevation of tumor necrosis factor-α and increased risk of recurrent coronary events after myocardial infarction. Circulation, 2000, 101, 2149-2153.
[http://dx.doi.org/10.1161/01.CIR.101.18.2149]
[56]
Nilsson, L.; Szymanowski, A.; Swahn, E.; Jonasson, L. Soluble TNF receptors are associated with infarct size and ventricular dysfunction in ST-elevation myocardial infarction. PLoS One, 2013, 8(2), e55477.
[http://dx.doi.org/10.1371/journal.pone.0055477] [PMID: 23405158]
[57]
Ruparelia, N.; Chai, J.T.; Fisher, E.A.; Choudhury, R.P. Inflammatory processes in cardiovascular disease: a route to targeted therapies. Nat. Rev. Cardiol., 2017, 14(3), 133-144.
[http://dx.doi.org/10.1038/nrcardio.2016.185] [PMID: 27905474]
[58]
Shamim, D.; Laskowski, M. Inhibition of inflammation mediated through the tumor necrosis factor α biochemical pathway can lead to favorable outcomes in Alzheimer disease. J. Cent. Nerv. Syst. Dis., 2017, 9, 1179573517722512.
[http://dx.doi.org/10.1177/1179573517722512] [PMID: 28811745]
[59]
Di Iorio, A.; Ferrucci, L.; Sparvieri, E.; Cherubini, A.; Volpato, S.; Corsi, A.; Bonafè, M.; Franceschi, C.; Abate, G.; Paganelli, R. Serum IL-1beta levels in health and disease: a population-based study. ‘The InCHIANTI study’. Cytokine, 2003, 22(6), 198-205.
[http://dx.doi.org/10.1016/S1043-4666(03)00152-2] [PMID: 12890453]
[60]
2012. Meta-Analysis, A. PLoS One, 2012, 7, e45641. Associations between interleukin-1 gene polymorphisms and coronary heart disease risk.
[http://dx.doi.org/10.1371/journal.pone.0045641] [PMID: 23029154]
[61]
Yoshimura, A.; Wakabayashi, Y.; Mori, T. Cellular and molecular basis for the regulation of inflammation by TGF-beta. J. Biochem., 2010, 147(6), 781-792.
[http://dx.doi.org/10.1093/jb/mvq043] [PMID: 20410014]
[62]
Rea, I.M.; Maxwell, L.D.; McNerlan, S.E.; Alexander, H.D.; Curran, M.D.; Middleton, D.; Ross, O.A. Killer immunoglobulin-like receptors (KIR) haplogroups A and B track with natural killer cells and cytokine profile in aged subjects: observations from octo/nonagenarians in the belfast elderly longitudinal free-living aging study (BELFAST). Immun. Ageing, 2013, 10(1), 35.
[http://dx.doi.org/10.1186/1742-4933-10-35] [PMID: 23957956]
[63]
Krieglstein, K.; Miyazono, K.; ten Dijke, P.; Unsicker, K. TGF-β in aging and disease. Cell Tissue Res., 2012, 347(1), 5-9.
[http://dx.doi.org/10.1007/s00441-011-1278-3] [PMID: 22183203]
[64]
Pastrana, J.L.; Sha, X.; Virtue, A.; Mai, J.; Cueto, R.; Lee, I.A.; Wang, H.; Yang, X. Regulatory T cells and atherosclerosis. J. Clin. Exp. Cardiolog, 2012, 2012, 012.
[65]
Burks, T.N.; Cohn, R.D. Role of TGF-β signaling in inherited and acquired myopathies. Skelet. Muscle, 2011, 1(1), 19.
[http://dx.doi.org/10.1186/2044-5040-1-19] [PMID: 21798096]
[66]
Baugé, C.; Girard, N.; Lhuissier, E.; Bazille, C.; Boumediene, K. Regulation and role of TGFβ signaling pathway in aging and osteoarthritis joints. Aging Dis., 2013, 5(6), 394-405.
[PMID: 25489490]
[67]
Doyle, K.P.; Cekanaviciute, E.; Mamer, L.E.; Buckwalter, M.S. TGFβ signaling in the brain increases with aging and signals to astrocytes and innate immune cells in the weeks after stroke. J. Neuroinflammation, 2010, 7, 62.
[http://dx.doi.org/10.1186/1742-2094-7-62] [PMID: 20937129]
[68]
Mallat, Z.; Gojova, A.; Marchiol-Fournigault, C.; Esposito, B.; Kamaté, C.; Merval, R.; Fradelizi, D.; Tedgui, A. Inhibition of transforming growth factor-beta signaling accelerates atherosclerosis and induces an unstable plaque phenotype in mice. Circ. Res., 2001, 89(10), 930-934.
[http://dx.doi.org/10.1161/hh2201.099415] [PMID: 11701621]
[69]
Tran, D.Q. TGF-β: the sword, the wand, and the shield of FOXP3(+) regulatory T cells. J. Mol. Cell Biol., 2012, 4(1), 29-37.
[http://dx.doi.org/10.1093/jmcb/mjr033] [PMID: 22158907]
[70]
Ouyang, W.; Rutz, S.; Crellin, N.K.; Valdez, P.A.; Hymowitz, S.G. Regulation and functions of the IL-10 family of cytokines in inflammation and disease. Annu. Rev. Immunol., 2011, 29, 71-109.
[http://dx.doi.org/10.1146/annurev-immunol-031210-101312] [PMID: 21166540]
[71]
Commins, S.; Steinke, J.W.; Borish, L. The extended IL-10 superfamily: IL-10, IL-19, IL-20, IL-22, IL-24, IL-26, IL-28, and IL-29. J. Allergy Clin. Immunol., 2008, 121(5), 1108-1111.
[http://dx.doi.org/10.1016/j.jaci.2008.02.026] [PMID: 18405958]
[72]
Sansoni, P.; Vescovini, R.; Fagnoni, F.; Biasini, C.; Zanni, F.; Zanlari, L.; Telera, A.; Lucchini, G.; Passeri, G.; Monti, D.; Franceschi, C.; Passeri, M. The immune system in extreme longevity. Exp. Gerontol., 2008, 43(2), 61-65.
[http://dx.doi.org/10.1016/j.exger.2007.06.008] [PMID: 17870272]
[73]
Rink, L.; Cakman, I.; Kirchner, H. Altered cytokine production in the elderly. Mech. Ageing Dev., 1998, 102(2-3), 199-209.
[http://dx.doi.org/10.1016/S0047-6374(97)00153-X] [PMID: 9720652]
[74]
Didion, S.P.; Kinzenbaw, D.A.; Schrader, L.I.; Chu, Y.; Faraci, F.M. Endogenous interleukin-10 inhibits angiotensin II-induced vascular dysfunction. Hypertension, 2009, 54(3), 619-624.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.109.137158] [PMID: 19620507]
[75]
Kinzenbaw, D.A.; Chu, Y.; Peña Silva, R.A.; Didion, S.P.; Faraci, F.M. Interleukin-10 protects against aging-induced endothelial dysfunction. Physiol. Rep., 2013, 1(6), e00149.
[http://dx.doi.org/10.1002/phy2.149] [PMID: 24400151]
[76]
Fichtlscherer, S.; Breuer, S.; Heeschen, C.; Dimmeler, S.; Zeiher, A.M. Interleukin-10 serum levels and systemic endothelial vasoreactivity in patients with coronary artery disease. J. Am. Coll. Cardiol., 2004, 44(1), 44-49.
[http://dx.doi.org/10.1016/j.jacc.2004.02.054] [PMID: 15234404]
[77]
Lio, D.; Scola, L.; Crivello, A.; Colonna-Romano, G.; Candore, G.; Bonafé, M.; Cavallone, L.; Marchegiani, F.; Olivieri, F.; Franceschi, C.; Caruso, C. Inflammation, genetics, and longevity: further studies on the protective effects in men of IL-10 -1082 promoter SNP and its interaction with TNF-α -308 promoter SNP. J. Med. Genet., 2003, 40(4), 296-299.
[http://dx.doi.org/10.1136/jmg.40.4.296] [PMID: 12676903]
[78]
Westendorp, R.G.; Langermans, J.A.; Huizinga, T.W.; Elouali, A.H.; Verweij, C.L.; Boomsma, D.I.; Vandenbroucke, J.P.; Vandenbrouke, J.P. Genetic influence on cytokine production and fatal meningococcal disease. Lancet, 1997, 349(9046), 170-173.
[http://dx.doi.org/10.1016/S0140-6736(96)06413-6] [PMID: 9111542]
[79]
Lakoski, S.G.; Liu, Y.; Brosnihan, K.B.; Herrington, D.M. Interleukin-10 concentration and coronary heart disease (CHD) event risk in the estrogen replacement and atherosclerosis (ERA) study. Atherosclerosis, 2008, 197(1), 443-447.
[http://dx.doi.org/10.1016/j.atherosclerosis.2007.06.033] [PMID: 17706223]
[80]
Welsh, P.; Murray, H.M.; Ford, I.; Trompet, S.; de Craen, A.J.M.; Jukema, J.W.; Stott, D.J.; McInnes, I.B.; Packard, C.J.; Westendorp, R.G.J.; Sattar, N. Circulating interleukin-10 and risk of cardiovascular events: a prospective study in the elderly at risk. Arterioscler. Thromb. Vasc. Biol., 2011, 31(10), 2338-2344.
[http://dx.doi.org/10.1161/ATVBAHA.111.231795] [PMID: 21757655]
[81]
Csiszar, A.; Ungvari, Z.; Edwards, J.G.; Kaminski, P.; Wolin, M.S.; Koller, A.; Kaley, G. Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ. Res., 2002, 90(11), 1159-1166.
[http://dx.doi.org/10.1161/01.RES.0000020401.61826.EA] [PMID: 12065318]
[82]
Ungvari, Z.; Orosz, Z.; Labinskyy, N.; Rivera, A.; Xiangmin, Z.; Smith, K.; Csiszar, A. Increased mitochondrial H2O2 production promotes endothelial NF-kappaB activation in aged rat arteries. Am. J. Physiol. Heart Circ. Physiol., 2007, 293(1), H37-H47.
[http://dx.doi.org/10.1152/ajpheart.01346.2006] [PMID: 17416599]
[83]
Csiszar, A.; Ungvari, Z.; Koller, A.; Edwards, J.G.; Kaley, G. Proinflammatory phenotype of coronary arteries promotes endothelial apoptosis in aging. Physiol. Genomics, 2004, 17(1), 21-30.
[http://dx.doi.org/10.1152/physiolgenomics.00136.2003] [PMID: 15020720]
[84]
Pearson, K.J.; Baur, J.A.; Lewis, K.N.; Peshkin, L.; Price, N.L.; Labinskyy, N.; Swindell, W.R.; Kamara, D.; Minor, R.K.; Perez, E.; Jamieson, H.A.; Zhang, Y.; Dunn, S.R.; Sharma, K.; Pleshko, N.; Woollett, L.A.; Csiszar, A.; Ikeno, Y.; Le Couteur, D.; Elliott, P.J.; Becker, K.G.; Navas, P.; Ingram, D.K.; Wolf, N.S.; Ungvari, Z.; Sinclair, D.A.; de Cabo, R. Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab., 2008, 8(2), 157-168.
[http://dx.doi.org/10.1016/j.cmet.2008.06.011] [PMID: 18599363]
[85]
Csiszar, A.; Ungvari, Z.; Koller, A.; Edwards, J.G.; Kaley, G. Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. FASEB J., 2003, 17(9), 1183-1185.
[http://dx.doi.org/10.1096/fj.02-1049fje] [PMID: 12709402]
[86]
Cernadas, M.R.; de Miguel, L.S.; García-Durán, M. González-Fernández, F.; Millás, I.; Montón, M.; Rodrigo, J.; Rico, L.; Fernández, P.; de Frutos, T.; Rodríguez-Feo, J.A. Expression of constitutive and inducible nitric oxide synthases in the vascular wall of young and aging rats. Circ. Res., 1998, 83, 279-286.
[87]
Wang, M.; Zhang, J.; Jiang, L-Q.; Spinetti, G.; Pintus, G.; Monticone, R.; Kolodgie, F.D.; Virmani, R.; Lakatta, E.G. Proinflammatory profile within the grossly normal aged human aortic wall. Hypertension, 2007, 50(1), 219-227.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.089409] [PMID: 17452499]
[88]
Miles, E.A.; Rees, D.; Banerjee, T.; Cazzola, R.; Lewis, S.; Wood, R.; Oates, R.; Tallant, A.; Cestaro, B.; Yaqoob, P.; Wahle, K.W.J.; Calder, P.C. Age-related increases in circulating inflammatory markers in men are independent of BMI, blood pressure and blood lipid concentrations. Atherosclerosis, 2008, 196(1), 298-305.
[http://dx.doi.org/10.1016/j.atherosclerosis.2006.11.002] [PMID: 17118371]
[89]
Csiszar, A.; Labinskyy, N.; Smith, K.; Rivera, A.; Orosz, Z.; Ungvari, Z. Vasculoprotective effects of anti-tumor necrosis factor-α treatment in aging. Am. J. Pathol., 2007, 170(1), 388-398.
[http://dx.doi.org/10.2353/ajpath.2007.060708] [PMID: 17200210]
[90]
Arenas, I.A.; Xu, Y.; Davidge, S.T. Age-associated impairment in vasorelaxation to fluid shear stress in the female vasculature is improved by TNF-alpha antagonism. Am. J. Physiol. Heart Circ. Physiol., 2006, 290(3), H1259-H1263.
[http://dx.doi.org/10.1152/ajpheart.00990.2005] [PMID: 16284227]
[91]
Straub, R.H.; Schradin, C. Chronic inflammatory systemic diseases: An evolutionary trade-off between acutely beneficial but chronically harmful programs. Evol. Med. Public Health, 2016, 2016(1), 37-51.
[http://dx.doi.org/10.1093/emph/eow001] [PMID: 26817483]
[92]
Beyer, I.; Mets, T.; Bautmans, I. Chronic low-grade inflammation and age-related sarcopenia. Curr. Opin. Clin. Nutr. Metab. Care, 2012, 15(1), 12-22.
[http://dx.doi.org/10.1097/MCO.0b013e32834dd297] [PMID: 22108098]
[93]
Sanada, F.; Taniyama, Y.; Muratsu, J.; Otsu, R.; Shimizu, H.; Rakugi, H.; Morishita, R. Source of chronic inflammation in aging. Front. Cardiovasc. Med., 2018, 5, 12.
[http://dx.doi.org/10.3389/fcvm.2018.00012] [PMID: 29564335]
[94]
Zhang, Q.; Raoof, M.; Chen, Y.; Sumi, Y.; Sursal, T.; Junger, W.; Brohi, K.; Itagaki, K.; Hauser, C.J. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 2010, 464(7285), 104-107.
[http://dx.doi.org/10.1038/nature08780] [PMID: 20203610]
[95]
Dall’Olio, F.; Vanhooren, V.; Chen, C.C.; Slagboom, P.E.; Wuhrer, M.; Franceschi, C. N-glycomic biomarkers of biological aging and longevity: a link with inflammaging. Ageing Res. Rev., 2013, 12(2), 685-698.
[http://dx.doi.org/10.1016/j.arr.2012.02.002] [PMID: 22353383]
[96]
Wang, G.C.; Kao, W.H.L.; Murakami, P.; Xue, Q-L.; Chiou, R.B.; Detrick, B.; McDyer, J.F.; Semba, R.D.; Casolaro, V.; Walston, J.D.; Fried, L.P. Cytomegalovirus infection and the risk of mortality and frailty in older women: a prospective observational cohort study. Am. J. Epidemiol., 2010, 171(10), 1144-1152.
[http://dx.doi.org/10.1093/aje/kwq062] [PMID: 20400465]
[97]
Kinross, J.; Nicholson, J.K. Gut microbiota: Dietary and social modulation of gut microbiota in the elderly. Nat. Rev. Gastroenterol. Hepatol., 2012, 9(10), 563-564.
[http://dx.doi.org/10.1038/nrgastro.2012.169] [PMID: 22945446]
[98]
Toward, R.; Montandon, S.; Walton, G.; Gibson, G.R. Effect of prebiotics on the human gut microbiota of elderly persons. Gut Microbes, 2012, 3(1), 57-60.
[http://dx.doi.org/10.4161/gmic.19411] [PMID: 22555548]
[99]
Claesson, M.J.; Cusack, S.; O’Sullivan, O.; Greene-Diniz, R.; de Weerd, H.; Flannery, E.; Marchesi, J.R.; Falush, D.; Dinan, T.; Fitzgerald, G.; Stanton, C.; van Sinderen, D.; O’Connor, M.; Harnedy, N.; O’Connor, K.; Henry, C.; O’Mahony, D.; Fitzgerald, A.P.; Shanahan, F.; Twomey, C.; Hill, C.; Ross, R.P.; O’Toole, P.W. Composition, variability, and temporal stability of the intestinal microbiota of the elderly. Proc. Natl. Acad. Sci. USA, 2011, 108(Suppl. 1), 4586-4591.
[http://dx.doi.org/10.1073/pnas.1000097107] [PMID: 20571116]
[100]
Shaw, A.C.; Goldstein, D.R.; Montgomery, R.R. Age-dependent dysregulation of innate immunity. Nat. Rev. Immunol., 2013, 13(12), 875-887.
[http://dx.doi.org/10.1038/nri3547] [PMID: 24157572]
[101]
Aw, D.; Silva, A.B.; Palmer, D.B. Immunosenescence: emerging challenges for an ageing population. Immunology, 2007, 120(4), 435-446.
[http://dx.doi.org/10.1111/j.1365-2567.2007.02555.x] [PMID: 17313487]
[102]
Gruver, A.L.; Hudson, L.L.; Sempowski, G.D. Immunosenescence of ageing. J. Pathol., 2007, 211(2), 144-156.
[http://dx.doi.org/10.1002/path.2104] [PMID: 17200946]
[103]
de Magalhães, J.P.; Passos, J.F. Stress, cell senescence and organismal ageing. Mech. Ageing Dev., 2018, 170, 2-9.
[http://dx.doi.org/10.1016/j.mad.2017.07.001] [PMID: 28688962]
[104]
Ungvari, Z.; Tarantini, S.; Hertelendy, P.; Valcarcel-Ares, M.N.; Fülöp, G.A.; Logan, S.; Kiss, T.; Farkas, E.; Csiszar, A.; Yabluchanskiy, A. Cerebromicrovascular dysfunction predicts cognitive decline and gait abnormalities in a mouse model of whole brain irradiation-induced accelerated brain senescence. Geroscience, 2017, 39(1), 33-42.
[http://dx.doi.org/10.1007/s11357-017-9964-z] [PMID: 28299642]
[105]
Roos, C.M.; Zhang, B.; Palmer, A.K.; Ogrodnik, M.B.; Pirtskhalava, T.; Thalji, N.M.; Hagler, M.; Jurk, D.; Smith, L.A.; Casaclang-Verzosa, G.; Zhu, Y.; Schafer, M.J.; Tchkonia, T.; Kirkland, J.L.; Miller, J.D. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell, 2016, 15(5), 973-977.
[http://dx.doi.org/10.1111/acel.12458] [PMID: 26864908]
[106]
Bhayadia, R.; Schmidt, B.M.W.; Melk, A.; Hömme, M. Senescence-induced oxidative stress causes endothelial dysfunction. J. Gerontol. A Biol. Sci. Med. Sci., 2016, 71(2), 161-169.
[http://dx.doi.org/10.1093/gerona/glv008] [PMID: 25735595]
[107]
Rossman, M.J.; Kaplon, R.E.; Hill, S.D.; McNamara, M.N.; Santos-Parker, J.R.; Pierce, G.L.; Seals, D.R.; Donato, A.J. Endothelial cell senescence with aging in healthy humans: prevention by habitual exercise and relation to vascular endothelial function. Am. J. Physiol. Heart Circ. Physiol., 2017, 313(5), H890-H895.
[http://dx.doi.org/10.1152/ajpheart.00416.2017] [PMID: 28971843]
[108]
Sanada, F.; Taniyama, Y.; Azuma, J.; Iekushi, K.; Dosaka, N.; Yokoi, T.; Koibuchi, N.; Kusunoki, H.; Aizawa, Y.; Morishita, R. Hepatocyte growth factor, but not vascular endothelial growth factor, attenuates angiotensin II-induced endothelial progenitor cell senescence. Hypertension, 2009, 53(1), 77-82.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.108.120725] [PMID: 19047582]
[109]
Tchkonia, T.; Zhu, Y.; van Deursen, J.; Campisi, J.; Kirkland, J.L. Cellular senescence and the senescent secretory phenotype: therapeutic opportunities. J. Clin. Invest., 2013, 123(3), 966-972.
[http://dx.doi.org/10.1172/JCI64098] [PMID: 23454759]
[110]
He, S.; Sharpless, N.E. Senescence in health and disease. Cell, 2017, 169(6), 1000-1011.
[http://dx.doi.org/10.1016/j.cell.2017.05.015] [PMID: 28575665]
[111]
Ungvari, Z.; Podlutsky, A.; Sosnowska, D.; Tucsek, Z.; Toth, P.; Deak, F.; Gautam, T.; Csiszar, A.; Sonntag, W.E. Ionizing radiation promotes the acquisition of a senescence-associated secretory phenotype and impairs angiogenic capacity in cerebromicrovascular endothelial cells: role of increased DNA damage and decreased DNA repair capacity in microvascular radiosensitivity. J. Gerontol. A Biol. Sci. Med. Sci., 2013, 68(12), 1443-1457.
[http://dx.doi.org/10.1093/gerona/glt057] [PMID: 23689827]
[112]
Childs, B.G.; Baker, D.J.; Wijshake, T.; Conover, C.A.; Campisi, J.; van Deursen, J.M. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science, 2016, 354(6311), 472-477.
[http://dx.doi.org/10.1126/science.aaf6659] [PMID: 27789842]
[113]
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(7372), 232-236.
[http://dx.doi.org/10.1038/nature10600] [PMID: 22048312]
[114]
Colón-Emeric, C.S.; Whitson, H.E.; Pavon, J.; Hoenig, H. Functional decline in older adults. Am. Fam. Physician, 2013, 88(6), 388-394.
[PMID: 24134046]
[115]
Freund, A.; Patil, C.K.; Campisi, J. p38MAPK is a novel DNA damage response-independent regulator of the senescence-associated secretory phenotype. EMBO J., 2011, 30(8), 1536-1548.
[http://dx.doi.org/10.1038/emboj.2011.69] [PMID: 21399611]
[116]
Kang, C.; Xu, Q.; Martin, T.D.; Li, M.Z.; Demaria, M.; Aron, L.; Lu, T.; Yankner, B.A.; Campisi, J.; Elledge, S.J. The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4. Science, 2015, 349(6255), aaa5612.
[http://dx.doi.org/10.1126/science.aaa5612] [PMID: 26404840]
[117]
Morgan, R.G.; Ives, S.J.; Lesniewski, L.A.; Cawthon, R.M.; Andtbacka, R.H.I.; Noyes, R.D.; Richardson, R.S.; Donato, A.J. Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries. Am. J. Physiol. Heart Circ. Physiol., 2013, 305(2), H251-H258.
[http://dx.doi.org/10.1152/ajpheart.00197.2013] [PMID: 23666675]
[118]
Song, Y.; Shen, H.; Schenten, D.; Shan, P.; Lee, P.J.; Goldstein, D.R. Aging enhances the basal production of IL-6 and CCL2 in vascular smooth muscle cells. Arterioscler. Thromb. Vasc. Biol., 2012, 32(1), 103-109.
[http://dx.doi.org/10.1161/ATVBAHA.111.236349] [PMID: 22034510]
[119]
Bailey-Downs, L.C.; Tucsek, Z.; Toth, P.; Sosnowska, D.; Gautam, T.; Sonntag, W.E.; Csiszar, A.; Ungvari, Z. Aging exacerbates obesity-induced oxidative stress and inflammation in perivascular adipose tissue in mice: a paracrine mechanism contributing to vascular redox dysregulation and inflammation. J. Gerontol. A Biol. Sci. Med. Sci., 2013, 68(7), 780-792.
[http://dx.doi.org/10.1093/gerona/gls238] [PMID: 23213032]
[120]
Tucsek, Z.; Toth, P.; Sosnowska, D.; Gautam, T.; Mitschelen, M.; Koller, A.; Szalai, G.; Sonntag, W.E.; Ungvari, Z.; Csiszar, A. Obesity in aging exacerbates blood-brain barrier disruption, neuroinflammation, and oxidative stress in the mouse hippocampus: effects on expression of genes involved in beta-amyloid generation and Alzheimer’s disease. J. Gerontol. A Biol. Sci. Med. Sci., 2014, 69(10), 1212-1226.
[http://dx.doi.org/10.1093/gerona/glt177] [PMID: 24269929]
[121]
Tucsek, Z.; Toth, P.; Tarantini, S.; Sosnowska, D.; Gautam, T.; Warrington, J.P.; Giles, C.B.; Wren, J.D.; Koller, A.; Ballabh, P.; Sonntag, W.E.; Ungvari, Z.; Csiszar, A. Aging exacerbates obesity-induced cerebromicrovascular rarefaction, neurovascular uncoupling, and cognitive decline in mice. J. Gerontol. A Biol. Sci. Med. Sci., 2014, 69(11), 1339-1352.
[http://dx.doi.org/10.1093/gerona/glu080] [PMID: 24895269]
[122]
Harman, D. Aging: a theory based on free radical and radiation chemistry. J. Gerontol., 1956, 11(3), 298-300.
[http://dx.doi.org/10.1093/geronj/11.3.298] [PMID: 13332224]
[123]
Daiber, A. Redox signaling (cross-talk) from and to mitochondria involves mitochondrial pores and reactive oxygen species. Biochim. Biophys. Acta, 2010, 1797(6-7), 897-906.
[http://dx.doi.org/10.1016/j.bbabio.2010.01.032] [PMID: 20122895]
[124]
Bedard, K.; Krause, K-H. The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol. Rev., 2007, 87(1), 245-313.
[http://dx.doi.org/10.1152/physrev.00044.2005] [PMID: 17237347]
[125]
Csiszar, A.; Wang, M.; Lakatta, E.G.; Ungvari, Z. Inflammation and endothelial dysfunction during aging: role of NF-kappaB. J. Appl. Physiol., 2008, 105(4), 1333-1341.
[http://dx.doi.org/10.1152/japplphysiol.90470.2008] [PMID: 18599677]
[126]
Takac, I.; Schröder, K.; Brandes, R.P. The Nox family of NADPH oxidases: friend or foe of the vascular system? Curr. Hypertens. Rep., 2012, 14(1), 70-78.
[http://dx.doi.org/10.1007/s11906-011-0238-3] [PMID: 22071588]
[127]
Babior, B.M.; Lambeth, J.D.; Nauseef, W. The neutrophil NADPH oxidase. Arch. Biochem. Biophys., 2002, 397(2), 342-344.
[http://dx.doi.org/10.1006/abbi.2001.2642] [PMID: 11795892]
[128]
Nguyen, G.T.; Green, E.R.; Mecsas, J. Neutrophils to the ROScue: mechanisms of NADPH oxidase activation and bacterial resistance. Front. Cell. Infect. Microbiol., 2017, 7, 373.
[http://dx.doi.org/10.3389/fcimb.2017.00373] [PMID: 28890882]
[129]
Drummond, G.R.; Sobey, C.G. Endothelial NADPH oxidases: which NOX to target in vascular disease? Trends Endocrinol. Metab., 2014, 25(9), 452-463.
[http://dx.doi.org/10.1016/j.tem.2014.06.012] [PMID: 25066192]
[130]
Youn, J-Y.; Zhang, J.; Zhang, Y.; Chen, H.; Liu, D.; Ping, P.; Weiss, J.N.; Cai, H. Oxidative stress in atrial fibrillation: an emerging role of NADPH oxidase. J. Mol. Cell. Cardiol., 2013, 62, 72-79.
[http://dx.doi.org/10.1016/j.yjmcc.2013.04.019] [PMID: 23643589]
[131]
Cho, K-J.; Seo, J-M.; Kim, J-H. Bioactive lipoxygenase metabolites stimulation of NADPH oxidases and reactive oxygen species. Mol. Cells, 2011, 32(1), 1-5.
[http://dx.doi.org/10.1007/s10059-011-1021-7] [PMID: 21424583]
[132]
Kienhöfer, J.; Häussler, D.J.F.; Ruckelshausen, F.; Muessig, E.; Weber, K.; Pimentel, D.; Ullrich, V.; Bürkle, A.; Bachschmid, M.M. Association of mitochondrial antioxidant enzymes with mitochondrial DNA as integral nucleoid constituents. FASEB J., 2009, 23(7), 2034-2044.
[http://dx.doi.org/10.1096/fj.08-113571] [PMID: 19228881]
[133]
Sohal, R.S.; Orr, W.C. The redox stress hypothesis of aging. Free Radic. Biol. Med., 2012, 52(3), 539-555.
[http://dx.doi.org/10.1016/j.freeradbiomed.2011.10.445] [PMID: 22080087]
[134]
Zhou, R.; Yazdi, A.S.; Menu, P.; Tschopp, J. A role for mitochondria in NLRP3 inflammasome activation. Nature, 2011, 469(7329), 221-225.
[http://dx.doi.org/10.1038/nature09663] [PMID: 21124315]
[135]
Tschopp, J. Mitochondria: Sovereign of inflammation? Eur. J. Immunol., 2011, 41(5), 1196-1202.
[http://dx.doi.org/10.1002/eji.201141436] [PMID: 21469137]
[136]
Abais, J.M.; Xia, M.; Zhang, Y.; Boini, K.M.; Li, P-L. Redox regulation of NLRP3 inflammasomes: ROS as trigger or effector? Antioxid. Redox Signal., 2015, 22(13), 1111-1129.
[http://dx.doi.org/10.1089/ars.2014.5994] [PMID: 25330206]
[137]
Hasegawa, Y.; Saito, T.; Ogihara, T.; Ishigaki, Y.; Yamada, T.; Imai, J.; Uno, K.; Gao, J.; Kaneko, K.; Shimosawa, T.; Asano, T.; Fujita, T.; Oka, Y.; Katagiri, H. Blockade of the nuclear factor-κB pathway in the endothelium prevents insulin resistance and prolongs life spans. Circulation, 2012, 125(9), 1122-1133.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.111.054346] [PMID: 22302838]
[138]
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(8), 518-527.
[http://dx.doi.org/10.1016/j.mad.2009.06.004] [PMID: 19549533]
[139]
Chen, H-Z.; Wang, F.; Gao, P.; Pei, J-F.; Liu, Y.; Xu, T-T.; Tang, X.; Fu, W-Y.; Lu, J.; Yan, Y-F.; Wang, X-M.; Han, L.; Zhang, Z-Q.; Zhang, R.; Zou, M-H.; Liu, D-P. Age-Associated sirtuin 1 reduction in vascular smooth muscle links vascular senescence and inflammation to abdominal aortic aneurysm. Circ. Res., 2016, 119(10), 1076-1088.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.308895] [PMID: 27650558]
[140]
Gano, L.B.; Donato, A.J.; Pasha, H.M.; Hearon, C.M., Jr; Sindler, A.L.; Seals, D.R. The SIRT1 activator SRT1720 reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice. Am. J. Physiol. Heart Circ. Physiol., 2014, 307(12), H1754-H1763.
[http://dx.doi.org/10.1152/ajpheart.00377.2014] [PMID: 25326534]
[141]
Ungvari, Z.; Bailey-Downs, L.; Gautam, T.; Sosnowska, D.; Wang, M.; Monticone, R.E.; Telljohann, R.; Pinto, J.T.; de Cabo, R.; Sonntag, W.E.; Lakatta, E.G.; Csiszar, A. Age-associated vascular oxidative stress, Nrf2 dysfunction, and NF-kappaB activation in the nonhuman primate Macaca mulatta. J. Gerontol. A Biol. Sci. Med. Sci., 2011, 66(8), 866-875.
[http://dx.doi.org/10.1093/gerona/glr092] [PMID: 21622983]
[142]
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(2), H363-H372.
[http://dx.doi.org/10.1152/ajpheart.01134.2010] [PMID: 21602469]
[143]
Ungvari, Z.; Bailey-Downs, L.; Gautam, T.; Jimenez, R.; Losonczy, G.; Zhang, C.; Ballabh, P.; Recchia, F.A.; Wilkerson, D.C.; Sonntag, W.E.; Pearson, K.; de Cabo, R.; Csiszar, A. Adaptive induction of NF-E2-related factor-2-driven antioxidant genes in endothelial cells in response to hyperglycemia. Am. J. Physiol. Heart Circ. Physiol., 2011, 300(4), H1133-H1140.
[http://dx.doi.org/10.1152/ajpheart.00402.2010] [PMID: 21217061]
[144]
Suh, J.H.; Shenvi, S.V.; Dixon, B.M.; Liu, H.; Jaiswal, A.K.; Liu, R-M.; Hagen, T.M. Decline in transcriptional activity of Nrf2 causes age-related loss of glutathione synthesis, which is reversible with lipoic acid. Proc. Natl. Acad. Sci. USA, 2004, 101(10), 3381-3386.
[http://dx.doi.org/10.1073/pnas.0400282101] [PMID: 14985508]
[145]
Mostoslavsky, R.; Chua, K.F.; Lombard, D.B.; Pang, W.W.; Fischer, M.R.; Gellon, L.; Liu, P.; Mostoslavsky, G.; Franco, S.; Murphy, M.M.; Mills, K.D.; Patel, P.; Hsu, J.T.; Hong, A.L.; Ford, E.; Cheng, H-L.; Kennedy, C.; Nunez, N.; Bronson, R.; Frendewey, D.; Auerbach, W.; Valenzuela, D.; Karow, M.; Hottiger, M.O.; Hursting, S.; Barrett, J.C.; Guarente, L.; Mulligan, R.; Demple, B.; Yancopoulos, G.D.; Alt, F.W. Genomic instability and aging-like phenotype in the absence of mammalian SIRT6. Cell, 2006, 124(2), 315-329.
[http://dx.doi.org/10.1016/j.cell.2005.11.044] [PMID: 16439206]
[146]
Valcarcel-Ares, M.N.; Gautam, T.; Warrington, J.P.; Bailey-Downs, L.; Sosnowska, D.; de Cabo, R.; Losonczy, G.; Sonntag, W.E.; Ungvari, Z.; Csiszar, A. Disruption of Nrf2 signaling impairs angiogenic capacity of endothelial cells: implications for microvascular aging. J. Gerontol. A Biol. Sci. Med. Sci., 2012, 67(8), 821-829.
[http://dx.doi.org/10.1093/gerona/glr229] [PMID: 22219515]
[147]
Ciechanover, A. Intracellular protein degradation: from a vague idea thru the lysosome and the ubiquitin-proteasome system and onto human diseases and drug targeting. Cell Death Differ., 2005, 12(9), 1178-1190.
[http://dx.doi.org/10.1038/sj.cdd.4401692] [PMID: 16094394]
[148]
Gelino, S.; Hansen, M. 2012.
[149]
Brunk, U.T.; Terman, A. The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis. Eur. J. Biochem., 2002, 269(8), 1996-2002.
[http://dx.doi.org/10.1046/j.1432-1033.2002.02869.x] [PMID: 11985575]
[150]
Carrard, G.; Bulteau, A-L.; Petropoulos, I.; Friguet, B. Impairment of proteasome structure and function in aging. Int. J. Biochem. Cell Biol., 2002, 34(11), 1461-1474.
[http://dx.doi.org/10.1016/S1357-2725(02)00085-7] [PMID: 12200039]
[151]
Rubinsztein, D.C.; Mariño, G.; Kroemer, G. Autophagy and aging. Cell, 2011, 146(5), 682-695.
[http://dx.doi.org/10.1016/j.cell.2011.07.030] [PMID: 21884931]
[152]
Mizushima, N.; Levine, B. Autophagy in Human Diseases. N. Engl. J. Med., 2020, 383(16), 1564-1576.
[http://dx.doi.org/10.1056/NEJMra2022774] [PMID: 33053285]
[153]
Wolfe, D.M.; Lee, J-H.; Kumar, A.; Lee, S.; Orenstein, S.J.; Nixon, R.A. Autophagy failure in Alzheimer’s disease and the role of defective lysosomal acidification. Eur. J. Neurosci., 2013, 37(12), 1949-1961.
[http://dx.doi.org/10.1111/ejn.12169] [PMID: 23773064]
[154]
Cuervo, A.M.; Macian, F. Autophagy and the immune function in aging. Curr. Opin. Immunol., 2014, 29, 97-104.
[http://dx.doi.org/10.1016/j.coi.2014.05.006] [PMID: 24929664]
[155]
Shi, C-S.; Shenderov, K.; Huang, N-N.; Kabat, J.; Abu-Asab, M.; Fitzgerald, K.A.; Sher, A.; Kehrl, J.H. Activation of autophagy by inflammatory signals limits IL-1β production by targeting ubiquitinated inflammasomes for destruction. Nat. Immunol., 2012, 13(3), 255-263.
[http://dx.doi.org/10.1038/ni.2215] [PMID: 22286270]
[156]
Zhong, Z.; Umemura, A.; Sanchez-Lopez, E.; Liang, S.; Shalapour, S.; Wong, J.; He, F.; Boassa, D.; Perkins, G.; Ali, S.R.; McGeough, M.D.; Ellisman, M.H.; Seki, E.; Gustafsson, A.B.; Hoffman, H.M.; Diaz-Meco, M.T.; Moscat, J.; Karin, M. NF-κB restricts inflammasome activation via elimination of damaged mitochondria. Cell, 2016, 164(5), 896-910.
[http://dx.doi.org/10.1016/j.cell.2015.12.057] [PMID: 26919428]
[157]
Blagosklonny, M.V. Linking calorie restriction to longevity through sirtuins and autophagy: any role for TOR. Cell Death Dis., 2010, 1, e12.
[http://dx.doi.org/10.1038/cddis.2009.17] [PMID: 21364614]
[158]
Blagosklonny, M.V. Rapamycin extends life- and health span because it slows aging. Aging (Albany NY), 2013, 5(8), 592-598.
[http://dx.doi.org/10.18632/aging.100591] [PMID: 23934728]
[159]
Zoncu, R.; Efeyan, A.; Sabatini, D.M. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat. Rev. Mol. Cell Biol., 2011, 12(1), 21-35.
[http://dx.doi.org/10.1038/nrm3025] [PMID: 21157483]
[160]
Fogarty, S.; Hardie, D.G. Development of protein kinase activators: AMPK as a target in metabolic disorders and cancer. Biochim. Biophys. Acta, 2010, 1804(3), 581-591.
[http://dx.doi.org/10.1016/j.bbapap.2009.09.012] [PMID: 19778642]
[161]
Guma, M.; Wang, Y.; Viollet, B.; Liu-Bryan, R. AMPK Activation by A-769662 controls IL-6 expression in inflammatory arthritis. PLoS One, 2015, 10(10), e0140452.
[http://dx.doi.org/10.1371/journal.pone.0140452] [PMID: 26474486]
[162]
Glossmann, H.H.; Lutz, O.M.D. Metformin and aging: a review. Gerontology, 2019, 65(6), 581-590.
[http://dx.doi.org/10.1159/000502257] [PMID: 31522175]
[163]
Vaiserman, A.M.; Marotta, F. Longevity-promoting pharmaceuticals: is it a time for implementation? Trends Pharmacol. Sci., 2016, 37(5), 331-333.
[http://dx.doi.org/10.1016/j.tips.2016.02.003] [PMID: 27113007]
[164]
Yan, Z.; Lira, V.A.; Greene, N.P. Exercise training-induced regulation of mitochondrial quality. Exerc. Sport Sci. Rev., 2012, 40(3), 159-164.
[http://dx.doi.org/10.1097/JES.0b013e3182575599] [PMID: 22732425]
[165]
Ferreira-Marques, M.; Aveleira, C.A.; Carmo-Silva, S.; Botelho, M.; Pereira de Almeida, L.; Cavadas, C. Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation. Aging (Albany NY), 2016, 8(7), 1470-1484.
[http://dx.doi.org/10.18632/aging.100996] [PMID: 27441412]
[166]
Durik, M.; Kavousi, M.; van der Pluijm, I.; Isaacs, A.; Cheng, C.; Verdonk, K.; Loot, A.E.; Oeseburg, H.; Bhaggoe, U.M.; Leijten, F.; van Veghel, R.; de Vries, R.; Rudez, G.; Brandt, R.; Ridwan, Y.R.; van Deel, E.D.; de Boer, M.; Tempel, D.; Fleming, I.; Mitchell, G.F.; Verwoert, G.C.; Tarasov, K.V.; Uitterlinden, A.G.; Hofman, A.; Duckers, H.J.; van Duijn, C.M.; Oostra, B.A.; Witteman, J.C.M.; Duncker, D.J.; Danser, A.H.; Hoeijmakers, J.H.; Roks, A.J.M. Nucleotide excision DNA repair is associated with age-related vascular dysfunction. Circulation, 2012, 126(4), 468-478.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.104380] [PMID: 22705887]
[167]
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(3), 1050-1056.
[http://dx.doi.org/10.1161/01.STR.0000257967.86132.01] [PMID: 17272762]
[168]
Morgan, R.G.; Ives, S.J.; Walker, A.E.; Cawthon, R.M.; Andtbacka, R.H.I.; Noyes, D.; Lesniewski, L.A.; Richardson, R.S.; Donato, A.J. Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping. J. Hypertens., 2014, 32(6), 1293-1299.
[http://dx.doi.org/10.1097/HJH.0000000000000157] [PMID: 24686009]
[169]
Martinet, W.; Knaapen, M.W.M.; De Meyer, G.R.Y.; Herman, A.G.; Kockx, M.M. Elevated levels of oxidative DNA damage and DNA repair enzymes in human atherosclerotic plaques. Circulation, 2002, 106(8), 927-932.
[http://dx.doi.org/10.1161/01.CIR.0000026393.47805.21] [PMID: 12186795]
[170]
Gray, K.; Kumar, S.; Figg, N.; Harrison, J.; Baker, L.; Mercer, J.; Littlewood, T.; Bennett, M. Effects of DNA damage in smooth muscle cells in atherosclerosis. Circ. Res., 2015, 116(5), 816-826.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.304921] [PMID: 25524056]
[171]
Ungvari, Z.; Kaley, G.; de Cabo, R.; Sonntag, W.E.; Csiszar, A. Mechanisms of vascular aging: new perspectives. J. Gerontol. A Biol. Sci. Med. Sci., 2010, 65(10), 1028-1041.
[http://dx.doi.org/10.1093/gerona/glq113] [PMID: 20576649]
[172]
Asai, K.; Kudej, R.K.; Shen, Y.T.; Yang, G.P.; Takagi, G.; Kudej, A.B.; Geng, Y.J.; Sato, N.; Nazareno, J.B.; Vatner, D.E.; Natividad, F.; Bishop, S.P.; Vatner, S.F. Peripheral vascular endothelial dysfunction and apoptosis in old monkeys. Arterioscler. Thromb. Vasc. Biol., 2000, 20(6), 1493-1499.
[http://dx.doi.org/10.1161/01.ATV.20.6.1493] [PMID: 10845863]
[173]
Meng, L.; Jin, W.; Wang, X. RIP3-mediated necrotic cell death accelerates systematic inflammation and mortality. Proc. Natl. Acad. Sci. USA, 2015, 112(35), 11007-11012.
[http://dx.doi.org/10.1073/pnas.1514730112] [PMID: 26283397]
[174]
Deepa, S.S.; Unnikrishnan, A.; Matyi, S.; Hadad, N.; Richardson, A. Necroptosis increases with age and is reduced by dietary restriction. Aging Cell, 2018, 17(4), e12770.
[http://dx.doi.org/10.1111/acel.12770] [PMID: 29696779]
[175]
Wang, Q.; Liu, Z.; Ren, J.; Morgan, S.; Assa, C.; Liu, B. Receptor-interacting protein kinase 3 contributes to abdominal aortic aneurysms via smooth muscle cell necrosis and inflammation. Circ. Res., 2015, 116(4), 600-611.
[http://dx.doi.org/10.1161/CIRCRESAHA.116.304899] [PMID: 25563840]
[176]
Spinetti, G.; Wang, M.; Monticone, R.; Zhang, J.; Zhao, D.; Lakatta, E.G. Rat aortic MCP-1 and its receptor CCR2 increase with age and alter vascular smooth muscle cell function. Arterioscler. Thromb. Vasc. Biol., 2004, 24(8), 1397-1402.
[http://dx.doi.org/10.1161/01.ATV.0000134529.65173.08] [PMID: 15178559]
[177]
Wang, M.; Takagi, G.; Asai, K.; Resuello, R.G.; Natividad, F.F.; Vatner, D.E.; Vatner, S.F.; Lakatta, E.G. Aging increases aortic MMP-2 activity and angiotensin II in nonhuman primates. Hypertension, 2003, 41(6), 1308-1316.
[http://dx.doi.org/10.1161/01.HYP.0000073843.56046.45] [PMID: 12743015]
[178]
Wang, M.; Zhang, J.; Spinetti, G.; Jiang, L-Q.; Monticone, R.; Zhao, D.; Cheng, L.; Krawczyk, M.; Talan, M.; Pintus, G.; Lakatta, E.G.; Angiotensin, I.I. Angiotensin II activates matrix metalloproteinase type II and mimics age-associated carotid arterial remodeling in young rats. Am. J. Pathol., 2005, 167(5), 1429-1442.
[http://dx.doi.org/10.1016/S0002-9440(10)61229-1] [PMID: 16251426]
[179]
Basso, N.; Cini, R.; Pietrelli, A.; Ferder, L.; Terragno, N.A.; Inserra, F. Protective effect of long-term angiotensin II inhibition. Am. J. Physiol. Heart Circ. Physiol., 2007, 293(3), H1351-H1358.
[http://dx.doi.org/10.1152/ajpheart.00393.2007] [PMID: 17557916]
[180]
de Cavanagh, E.M.V.; Inserra, F.; Ferder, L.; Angiotensin, I.I. Angiotensin II blockade: how its molecular targets may signal to mitochondria and slow aging. Coincidences with calorie restriction and mTOR inhibition. Am. J. Physiol. Heart Circ. Physiol., 2015, 309(1), H15-H44.
[http://dx.doi.org/10.1152/ajpheart.00459.2014] [PMID: 25934099]
[181]
Benigni, A.; Corna, D.; Zoja, C.; Sonzogni, A.; Latini, R.; Salio, M.; Conti, S.; Rottoli, D.; Longaretti, L.; Cassis, P.; Morigi, M.; Coffman, T.M.; Remuzzi, G. Disruption of the Ang II type 1 receptor promotes longevity in mice. J. Clin. Invest., 2009, 119(3), 524-530.
[http://dx.doi.org/10.1172/JCI36703] [PMID: 19197138]
[182]
Siasos, G.; Tsigkou, V.; Kosmopoulos, M.; Theodosiadis, D.; Simantiris, S.; Tagkou, N.M.; Tsimpiktsioglou, A.; Stampouloglou, P.K.; Oikonomou, E.; Mourouzis, K.; Philippou, A.; Vavuranakis, M.; Stefanadis, C.; Tousoulis, D.; Papavassiliou, A.G. Mitochondria and cardiovascular diseases-from pathophysiology to treatment. Ann. Transl. Med., 2018, 6(12), 256.
[http://dx.doi.org/10.21037/atm.2018.06.21] [PMID: 30069458]
[183]
Toth, P.; Tarantini, S.; Springo, Z.; Tucsek, Z.; Gautam, T.; Giles, C.B.; Wren, J.D.; Koller, A.; Sonntag, W.E.; Csiszar, A.; Ungvari, Z. Aging exacerbates hypertension-induced cerebral microhemorrhages in mice: role of resveratrol treatment in vasoprotection. Aging Cell, 2015, 14(3), 400-408.
[http://dx.doi.org/10.1111/acel.12315] [PMID: 25677910]
[184]
Kumar, S.; Dietrich, N.; Kornfeld, K. Angiotensin converting enzyme (ACE) inhibitor extends Caenorhabditis elegans life Span. PLoS Genet., 2016, 12(2), e1005866.
[http://dx.doi.org/10.1371/journal.pgen.1005866] [PMID: 26918946]
[185]
Woll, P.S.; Morris, J.K.; Painschab, M.S.; Marcus, R.K.; Kohn, A.D.; Biechele, T.L.; Moon, R.T.; Kaufman, D.S. Wnt signaling promotes hematoendothelial cell development from human embryonic stem cells. Blood, 2008, 111(1), 122-131.
[http://dx.doi.org/10.1182/blood-2007-04-084186] [PMID: 17875805]
[186]
Cheng, C.W.; Yeh, J.C.; Fan, T-P.; Smith, S.K.; Charnock-Jones, D.S. Wnt5a-mediated non-canonical Wnt signalling regulates human endothelial cell proliferation and migration. Biochem. Biophys. Res. Commun., 2008, 365(2), 285-290.
[http://dx.doi.org/10.1016/j.bbrc.2007.10.166] [PMID: 17986384]
[187]
Brigstock, D.R. Regulation of angiogenesis and endothelial cell function by connective tissue growth factor (CTGF) and cysteine-rich 61 (CYR61). Angiogenesis, 2002, 5(3), 153-165.
[http://dx.doi.org/10.1023/A:1023823803510] [PMID: 12831056]
[188]
Li, F.; Chong, Z.Z.; Maiese, K. Winding through the WNT pathway during cellular development and demise. Histol. Histopathol., 2006, 21(1), 103-124.
[PMID: 16267791]
[189]
Kang, J-Q.; Chong, Z.Z.; Maiese, K. Critical role for Akt1 in the modulation of apoptotic phosphatidylserine exposure and microglial activation. Mol. Pharmacol., 2003, 64(3), 557-569.
[http://dx.doi.org/10.1124/mol.64.3.557] [PMID: 12920191]
[190]
Chong, Z.Z.; Kang, J-Q.; Maiese, K. AKT1 drives endothelial cell membrane asymmetry and microglial activation through Bcl-xL and caspase 1, 3, and 9. Exp. Cell Res., 2004, 296(2), 196-207.
[http://dx.doi.org/10.1016/j.yexcr.2004.01.021] [PMID: 15149850]
[191]
Chong, Z.Z.; Li, F.; Maiese, K. The pro-survival pathways of mTOR and protein kinase B target glycogen synthase kinase-3beta and nuclear factor-kappaB to foster endogenous microglial cell protection. Int. J. Mol. Med., 2007, 19(2), 263-272.
[PMID: 17203200]
[192]
Li, F.; Chong, Z.Z.; Maiese, K. Microglial integrity is maintained by erythropoietin through integration of Akt and its substrates of glycogen synthase kinase-3beta, beta-catenin, and nuclear factor-kappaB. Curr. Neurovasc. Res., 2006, 3(3), 187-201.
[http://dx.doi.org/10.2174/156720206778018758] [PMID: 16918383]
[193]
Li, F.; Chong, Z.Z.; Maiese, K. Vital elements of the Wnt-Frizzled signaling pathway in the nervous system. Curr. Neurovasc. Res., 2005, 2(4), 331-340.
[http://dx.doi.org/10.2174/156720205774322557] [PMID: 16181124]
[194]
Mallat, M.; Marín-Teva, J.L.; Chéret, C. Phagocytosis in the developing CNS: more than clearing the corpses. Curr. Opin. Neurobiol., 2005, 15(1), 101-107.
[http://dx.doi.org/10.1016/j.conb.2005.01.006] [PMID: 15721751]
[195]
Dringen, R. Oxidative and antioxidative potential of brain microglial cells. Antioxid. Redox Signal., 2005, 7(9-10), 1223-1233.
[http://dx.doi.org/10.1089/ars.2005.7.1223] [PMID: 16115027]
[196]
Sankarapandi, S.; Zweier, J.L.; Mukherjee, G.; Quinn, M.T.; Huso, D.L. Measurement and characterization of superoxide generation in microglial cells: evidence for an NADPH oxidase-dependent pathway. Arch. Biochem. Biophys., 1998, 353(2), 312-321.
[http://dx.doi.org/10.1006/abbi.1998.0658] [PMID: 9606965]
[197]
Lobov, I.B.; Rao, S.; Carroll, T.J.; Vallance, J.E.; Ito, M.; Ondr, J.K.; Kurup, S.; Glass, D.A.; Patel, M.S.; Shu, W.; Morrisey, E.E.; McMahon, A.P.; Karsenty, G.; Lang, R.A. WNT7b mediates macrophage-induced programmed cell death in patterning of the vasculature. Nature, 2005, 437(7057), 417-421.
[http://dx.doi.org/10.1038/nature03928] [PMID: 16163358]
[198]
Chong, Z.Z.; Li, F.; Maiese, K. Cellular demise and inflammatory microglial activation during beta-amyloid toxicity are governed by Wnt1 and canonical signaling pathways. Cell. Signal., 2007, 19(6), 1150-1162.
[http://dx.doi.org/10.1016/j.cellsig.2006.12.009] [PMID: 17289346]
[199]
Ungvari, Z.; Labinskyy, N.; Mukhopadhyay, P.; Pinto, J.T.; Bagi, Z.; Ballabh, P.; Zhang, C.; Pacher, P.; Csiszar, A. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am. J. Physiol. Heart Circ. Physiol., 2009, 297(5), H1876-H1881.
[http://dx.doi.org/10.1152/ajpheart.00375.2009] [PMID: 19749157]
[200]
Csiszar, A.; Labinskyy, N.; Pinto, J.T.; Ballabh, P.; Zhang, H.; Losonczy, G.; Pearson, K.; de Cabo, R.; Pacher, P.; Zhang, C.; Ungvari, Z. Resveratrol induces mitochondrial biogenesis in endothelial cells. Am. J. Physiol. Heart Circ. Physiol., 2009, 297(1), H13-H20.
[http://dx.doi.org/10.1152/ajpheart.00368.2009] [PMID: 19429820]
[201]
Lee, I.H.; Cao, L.; Mostoslavsky, R.; Lombard, D.B.; Liu, J.; Bruns, N.E.; Tsokos, M.; Alt, F.W.; Finkel, T. A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy. Proc. Natl. Acad. Sci. USA, 2008, 105(9), 3374-3379.
[http://dx.doi.org/10.1073/pnas.0712145105] [PMID: 18296641]
[202]
de Picciotto, N.E.; Gano, L.B.; Johnson, L.C.; Martens, C.R.; Sindler, A.L.; Mills, K.F.; Imai, S.; Seals, D.R. Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice. Aging Cell, 2016, 15(3), 522-530.
[http://dx.doi.org/10.1111/acel.12461] [PMID: 26970090]
[203]
Donato, A.J.; Magerko, K.A.; Lawson, B.R.; Durrant, J.R.; Lesniewski, L.A.; Seals, D.R. SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans. J. Physiol., 2011, 589(Pt 18), 4545-4554.
[http://dx.doi.org/10.1113/jphysiol.2011.211219] [PMID: 21746786]
[204]
Fry, J.L.; Al Sayah, L.; Weisbrod, R.M.; Van Roy, I.; Weng, X.; Cohen, R.A.; Bachschmid, M.M.; Seta, F. Vascular smooth muscle sirtuin-1 protects against diet-induced aortic stiffness. Hypertension, 2016, 68(3), 775-784.
[http://dx.doi.org/10.1161/HYPERTENSIONAHA.116.07622] [PMID: 27432859]
[205]
Chen, Y.X.; Zhang, M.; Cai, Y.; Zhao, Q.; Dai, W. The Sirt1 activator SRT1720 attenuates angiotensin II-induced atherosclerosis in apoE−/− mice through inhibiting vascular inflammatory response. Biochem. Biophys. Res. Commun., 2015, 465(4), 732-738.
[http://dx.doi.org/10.1016/j.bbrc.2015.08.066] [PMID: 26296466]
[206]
Baur, J.A.; Ungvari, Z.; Minor, R.K.; Le Couteur, D.G.; de Cabo, R. Are sirtuins viable targets for improving healthspan and lifespan? Nat. Rev. Drug Discov., 2012, 11(6), 443-461.
[http://dx.doi.org/10.1038/nrd3738] [PMID: 22653216]
[207]
Gorenne, I.; Kumar, S.; Gray, K.; Figg, N.; Yu, H.; Mercer, J.; Bennett, M. Vascular smooth muscle cell sirtuin 1 protects against DNA damage and inhibits atherosclerosis. Circulation, 2013, 127(3), 386-396.
[http://dx.doi.org/10.1161/CIRCULATIONAHA.112.124404] [PMID: 23224247]
[208]
Xu, S.; Yin, M.; Koroleva, M.; Mastrangelo, M.A.; Zhang, W.; Bai, P.; Little, P.J.; Jin, Z.G. SIRT6 protects against endothelial dysfunction and atherosclerosis in mice. Aging (Albany NY), 2016, 8(5), 1064-1082.
[http://dx.doi.org/10.18632/aging.100975] [PMID: 27249230]
[209]
Cardus, A.; Uryga, A.K.; Walters, G.; Erusalimsky, J.D. SIRT6 protects human endothelial cells from DNA damage, telomere dysfunction, and senescence. Cardiovasc. Res., 2013, 97(3), 571-579.
[http://dx.doi.org/10.1093/cvr/cvs352] [PMID: 23201774]
[210]
Das, D.K.; Maulik, N. Resveratrol in cardioprotection: a therapeutic promise of alternative medicine. Mol. Interv., 2006, 6(1), 36-47.
[http://dx.doi.org/10.1124/mi.6.1.7] [PMID: 16507749]
[211]
Stivala, L.A.; Savio, M.; Carafoli, F.; Perucca, P.; Bianchi, L.; Maga, G.; Forti, L.; Pagnoni, U.M.; Albini, A.; Prosperi, E.; Vannini, V. Specific structural determinants are responsible for the antioxidant activity and the cell cycle effects of resveratrol. J. Biol. Chem., 2001, 276(25), 22586-22594.
[http://dx.doi.org/10.1074/jbc.M101846200] [PMID: 11316812]
[212]
Yoshino, J.; Mills, K.F.; Yoon, M.J.; Imai, S. Nicotinamide mononucleotide, a key NAD(+) intermediate, treats the pathophysiology of diet- and age-induced diabetes in mice. Cell Metab., 2011, 14(4), 528-536.
[http://dx.doi.org/10.1016/j.cmet.2011.08.014] [PMID: 21982712]
[213]
Johnson, S.C.; Sangesland, M.; Kaeberlein, M.; Rabinovitch, P.S. Modulating mTOR in aging and health. Interdiscip. Top. Gerontol., 2015, 40, 107-127.
[http://dx.doi.org/10.1159/000364974] [PMID: 25341517]
[214]
Caccamo, A.; Majumder, S.; Richardson, A.; Strong, R.; Oddo, S. Molecular interplay between mammalian target of rapamycin (mTOR), amyloid-beta, and Tau: effects on cognitive impairments. J. Biol. Chem., 2010, 285(17), 13107-13120.
[http://dx.doi.org/10.1074/jbc.M110.100420] [PMID: 20178983]
[215]
Lin, A-L.; Zheng, W.; Halloran, J.J.; Burbank, R.R.; Hussong, S.A.; Hart, M.J.; Javors, M.; Shih, Y-Y.I.; Muir, E.; Solano Fonseca, R.; Strong, R.; Richardson, A.G.; Lechleiter, J.D.; Fox, P.T.; Galvan, V. Chronic rapamycin restores brain vascular integrity and function through NO synthase activation and improves memory in symptomatic mice modeling Alzheimer’s disease. J. Cereb. Blood Flow Metab., 2013, 33(9), 1412-1421.
[http://dx.doi.org/10.1038/jcbfm.2013.82] [PMID: 23801246]
[216]
Wang, C-Y.; Kim, H-H.; Hiroi, Y.; Sawada, N.; Salomone, S.; Benjamin, L.E.; Walsh, K.; Moskowitz, M.A.; Liao, J.K. Obesity increases vascular senescence and susceptibility to ischemic injury through chronic activation of Akt and mTOR. Sci. Signal., 2009, 2(62), ra11.
[http://dx.doi.org/10.1126/scisignal.2000143] [PMID: 19293429]
[217]
Yepuri, G.; Velagapudi, S.; Xiong, Y.; Rajapakse, A.G.; Montani, J-P.; Ming, X-F.; Yang, Z. Positive crosstalk between arginase-II and S6K1 in vascular endothelial inflammation and aging. Aging Cell, 2012, 11(6), 1005-1016.
[http://dx.doi.org/10.1111/acel.12001] [PMID: 22928666]
[218]
Lesniewski, L.A.; Seals, D.R.; Walker, A.E.; Henson, G.D.; Blimline, M.W.; Trott, D.W.; Bosshardt, G.C.; LaRocca, T.J.; Lawson, B.R.; Zigler, M.C.; Donato, A.J. Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways. Aging Cell, 2017, 16(1), 17-26.
[http://dx.doi.org/10.1111/acel.12524] [PMID: 27660040]
[219]
Jahrling, J.B.; Lin, A-L.; DeRosa, N.; Hussong, S.A.; Van Skike, C.E.; Girotti, M.; Javors, M.; Zhao, Q.; Maslin, L.A.; Asmis, R.; Galvan, V. mTOR drives cerebral blood flow and memory deficits in LDLR-/- mice modeling atherosclerosis and vascular cognitive impairment. J. Cereb. Blood Flow Metab., 2018, 38(1), 58-74.
[http://dx.doi.org/10.1177/0271678X17705973] [PMID: 28511572]
[220]
Zhang, W.; Khatibi, N.H.; Yamaguchi-Okada, M.; Yan, J.; Chen, C.; Hu, Q.; Meng, H.; Han, H.; Liu, S.; Zhou, C. Mammalian target of rapamycin (mTOR) inhibition reduces cerebral vasospasm following a subarachnoid hemorrhage injury in canines. Exp. Neurol., 2012, 233(2), 799-806.
[http://dx.doi.org/10.1016/j.expneurol.2011.11.046] [PMID: 22177999]
[221]
Fletcher, L.; Evans, T.M.; Watts, L.T.; Jimenez, D.F.; Digicaylioglu, M. Rapamycin treatment improves neuron viability in an in vitro model of stroke. PLoS One, 2013, 8(7), e68281.
[http://dx.doi.org/10.1371/journal.pone.0068281] [PMID: 23861877]
[222]
Yin, L.; Ye, S.; Chen, Z.; Zeng, Y. Rapamycin preconditioning attenuates transient focal cerebral ischemia/reperfusion injury in mice. Int. J. Neurosci., 2012, 122(12), 748-756.
[http://dx.doi.org/10.3109/00207454.2012.721827] [PMID: 22901235]
[223]
Hattori, Y.; Suzuki, K.; Hattori, S.; Kasai, K. Metformin inhibits cytokine-induced nuclear factor kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells. Hypertension, 2006, 47(6), 1183-1188.
[http://dx.doi.org/10.1161/01.HYP.0000221429.94591.72] [PMID: 16636195]
[224]
Hardie, D.G.; Hawley, S.A.; Scott, J.W. AMP-activated protein kinase-development of the energy sensor concept. J. Physiol., 2006, 574(Pt 1), 7-15.
[http://dx.doi.org/10.1113/jphysiol.2006.108944] [PMID: 16644800]
[225]
Lesniewski, L.A.; Zigler, M.C.; Durrant, J.R.; Donato, A.J.; Seals, D.R. Sustained activation of AMPK ameliorates age-associated vascular endothelial dysfunction via a nitric oxide-independent mechanism. Mech. Ageing Dev., 2012, 133(5), 368-371.
[http://dx.doi.org/10.1016/j.mad.2012.03.011] [PMID: 22484146]
[226]
Pu, Y.; Zhang, H.; Wang, P.; Zhao, Y.; Li, Q.; Wei, X.; Cui, Y.; Sun, J.; Shang, Q.; Liu, D.; Zhu, Z. Dietary curcumin ameliorates aging-related cerebrovascular dysfunction through the AMPK/uncoupling protein 2 pathway. Cell. Physiol. Biochem., 2013, 32(5), 1167-1177.
[http://dx.doi.org/10.1159/000354516] [PMID: 24335167]
[227]
Chen, Z.P.; Mitchelhill, K.I.; Michell, B.J.; Stapleton, D.; Rodriguez-Crespo, I.; Witters, L.A.; Power, D.A.; Ortiz de Montellano, P.R.; Kemp, B.E. AMP-activated protein kinase phosphorylation of endothelial NO synthase. FEBS Lett., 1999, 443(3), 285-289.
[http://dx.doi.org/10.1016/S0014-5793(98)01705-0] [PMID: 10025949]
[228]
Chen, Z.; Peng, I-C.; Sun, W.; Su, M-I.; Hsu, P-H.; Fu, Y.; Zhu, Y.; DeFea, K.; Pan, S.; Tsai, M-D.; Shyy, J.Y-J. AMP-activated protein kinase functionally phosphorylates endothelial nitric oxide synthase Ser633. Circ. Res., 2009, 104(4), 496-505.
[http://dx.doi.org/10.1161/CIRCRESAHA.108.187567] [PMID: 19131647]
[229]
Levine, Y.C.; Li, G.K.; Michel, T. Agonist-modulated regulation of AMP-activated protein kinase (AMPK) in endothelial cells. Evidence for an AMPK -> Rac1 -> Akt -> endothelial nitric-oxide synthase pathway. J. Biol. Chem., 2007, 282(28), 20351-20364.
[http://dx.doi.org/10.1074/jbc.M702182200] [PMID: 17519230]

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