Skip to main content

Advertisement

SpringerLink
Log in

Hypertension and cellular senescence

  • Review article
  • Published:
Biogerontology Aims and scope Submit manuscript

Abstract

Essential or primary hypertension is a wordwide health problem. Elevated blood pressure (BP) is closely associated not only with increased chronological aging but also with biological aging. There are various common pathways that play a role in cellular aging and BP regulation. These include but not limited to inflammation, oxidative stress, mitochondrial dysfunction, air pollution, decreased klotho activity increased renin angiotensin system activation, gut dysbiosis etc. It has already been shown that some anti-hypertensive drugs have anti-senescent actions and some senolytic drugs have BP lowering effects. In this review, we have summarized the common mechanisms underlying cellular senescence and HT and their relationships. We further reviewed the effect of various antihypertensive medications on cellular senescence and suggest further issues to be studied.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

Data availability

Not applicable. No data are reported in this manuscript.

References

  • Abada A, Elazar Z (2014) Getting ready for building: signaling and autophagosome biogenesis. EMBO Rep 15:839–852

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Abbas M, Jesel L, Auger C, Amoura L, Messas N, Manin G, Rumig C, León-González AJ, Ribeiro TP, Silva GC, Abou-Merhi R, Hamade E, Hecker M, Georg Y, Chakfe N, Ohlmann P, Schini-Kerth VB, Toti F, Morel O (2017) Endothelial microparticles from acute coronary syndrome patients induce premature coronary artery endothelial cell aging and thrombogenicity: role of the Ang II/AT1 Receptor/NADPH oxidase-mediated activation of MAPKs and PI3-kinase pathways. Circulation 135:280–296

    Article  CAS  PubMed  Google Scholar 

  • Abdul Y, Karakaya E, Chandran R, Jamil S, Ergul A (2022) Endothelin A receptors contribute to senescence of brain microvascular endothelial cells. Can J Physiol Pharmacol 100:1087–1096

    Article  CAS  PubMed  Google Scholar 

  • Adijiang A, Shimizu H, Higuchi Y, Nishijima F, Niwa T (2011) Indoxyl sulfate reduces klotho expression and promotes senescence in the kidneys of hypertensive rats. J Ren Nutr 21:105–109

    Article  CAS  PubMed  Google Scholar 

  • Adnan S, Nelson JW, Ajami NJ, Venna VR, Petrosino JF, Bryan RM Jr, Durgan DJ (2017) Alterations in the gut microbiota can elicit hypertension in rats. Physiol Genomics 49:96–104

    Article  CAS  PubMed  Google Scholar 

  • Afsar B, Vaziri ND, Aslan G, Tarim K, Kanbay M (2016) Gut hormones and gut microbiota: implications for kidney function and hypertension. J Am Soc Hypertens 10:954–961

    Article  CAS  PubMed  Google Scholar 

  • Afsar B, Kuwabara M, Ortiz A, Yerlikaya A, Siriopol D, Covic A, Rodriguez-Iturbe B, Johnson RJ, Kanbay M (2018) Salt intake and immunity. Hypertension 72:19–23

    Article  CAS  PubMed  Google Scholar 

  • Ahluwalia A, Patel K, Hoa N, Brzozowska I, Jones MK, Tarnawski AS (2021) Melatonin ameliorates aging-related impaired angiogenesis in gastric endothelial cells via local actions on mitochondria and VEGF-survivin signaling. Am J Physiol Gastrointest Liver Physiol 321:G682-g689

    Article  CAS  PubMed  Google Scholar 

  • Aksoy P, White TA, Thompson M, Chini EN (2006) Regulation of intracellular levels of NAD: a novel role for CD38. Biochem Biophys Res Commun 345:1386–1392

    Article  CAS  PubMed  Google Scholar 

  • Alesutan I, Feger M, Pakladok T, Mia S, Ahmed MS, Voelkl J, Lang F (2013) 25-Hydroxyvitamin D3 1-α-hydroxylase-dependent stimulation of renal klotho expression by spironolactone. Kidney Blood Press Res 37:475–487

    Article  CAS  PubMed  Google Scholar 

  • Altamirano FG, Castro-Pascual IC, Ferramola ML, Tula ML, Delgado SM, Anzulovich AC, Lacoste MG (2021) Aging disrupts the temporal organization of antioxidant defenses in the heart of male rats and phase shifts circadian rhythms of systolic blood pressure. Biogerontology 22:603–621

    Article  CAS  PubMed  Google Scholar 

  • Antunes BM, Rossi FE, Cholewa JM, Lira FS (2016) Regular physical activity and vascular aging. Curr Pharm Des 22:3715–3729

    Article  CAS  PubMed  Google Scholar 

  • Aroor AR, Jia G, Habibi J, Sun Z, Ramirez-Perez FI, Brady B, Chen D, Martinez-Lemus LA, Manrique C, Nistala R, Whaley-Connell AT, Demarco VG, Meininger GA, Sowers JR (2017) Uric acid promotes vascular stiffness, maladaptive inflammatory responses and proteinuria in western diet fed mice. Metabolism 74:32–40

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Assavanopakun P, Sapbamrer R, Kumfu S, Chattipakorn N, Chattipakorn SC (2022) Effects of air pollution on telomere length: Evidence from in vitro to clinical studies. Environ Pollut 312:120096

    Article  CAS  PubMed  Google Scholar 

  • Aviv A (2002) Salt consumption, reactive oxygen species and cardiovascular ageing: a hypothetical link. J Hypertens 20:555–559

    Article  CAS  PubMed  Google Scholar 

  • Baiardi G, Bregonzio C, Jezova M, Armando I, Saavedra JM (2004) Angiotensin II AT1 receptor blockade prolongs the lifespan of spontaneously hypertensive rats and reduces stress-induced release of catecholamines, glucocorticoids, and vasopressin. Ann N Y Acad Sci 1018:131–136

    Article  CAS  PubMed  Google Scholar 

  • Battelli MG, Bortolotti M, Bolognesi A, Polito L (2020) Pro-aging effects of xanthine oxidoreductase products. Antioxidants (Basel) 9:839

    Article  CAS  PubMed  Google Scholar 

  • Benetos A, Gardner JP, Kimura M, Labat C, Nzietchueng R, Dousset B, Zannad F, Lacolley P, Aviv A (2005) Aldosterone and telomere length in white blood cells. J Gerontol A Biol Sci Med Sci 60:1593–1596

    Article  PubMed  Google Scholar 

  • Bhayadia R, Schmidt BM, Melk A, Hömme M (2016) Senescence-induced oxidative stress causes endothelial dysfunction. J Gerontol A Biol Sci Med Sci 71:161–169

    Article  CAS  PubMed  Google Scholar 

  • Bhoumik S, Kesherwani R, Kumar R, Rizvi SI (2022) Alternate day fasting and time-restricted feeding may confer similar neuroprotective effects during aging in male rats. Biogerontology 23:757–770

    Article  CAS  PubMed  Google Scholar 

  • Bhupatiraju C, Saini D, Patkar S, Deepak P, Das B, Padma T (2012) Association of shorter telomere length with essential hypertension in Indian population. Am J Hum Biol 24:573–578

    Article  PubMed  Google Scholar 

  • Boeno FP, Ramis TR, Munhoz SV, Farinha JB, Moritz CEJ, Leal-Menezes R, Ribeiro JL, Christou DD, Reischak-Oliveira A (2020) Effect of aerobic and resistance exercise training on inflammation, endothelial function and ambulatory blood pressure in middle-aged hypertensive patients. J Hypertens 38:2501–2509

    Article  CAS  PubMed  Google Scholar 

  • Bomfim GHS, Musial DC, Méndez-López I, Jurkiewicz A, Jurkiewicz NH, Padín JF, García AG (2020) Chronic resveratrol consumption prevents hypertension development altering electrophysiological currents and Ca(2+) signaling in chromaffin cells from SHR rats. Cell Signal 76:109811

    Article  CAS  PubMed  Google Scholar 

  • Brandt M, Dörschmann H, Khraisat S, Knopp T, Ringen J, Kalinovic S, Garlapati V, Siemer S, Molitor M, Göbel S, Stauber R, Karbach SH, Münzel T, Daiber A, Wenzel P (2022) Telomere shortening in hypertensive heart disease depends on oxidative DNA damage and predicts impaired recovery of cardiac function in heart failure. Hypertension 79:2173–2184

    Article  CAS  PubMed  Google Scholar 

  • Calò LA, Dal Maso L, Pagnin E, Ravarotto V, Facco M, Boscaro E, Maiolino G, Pessina AC, Rossi GP (2014) Effect of olmesartan medoxomil on number and survival of circulating endothelial progenitor cells and calcitonin gene related peptide in hypertensive patients. J Hypertens 32:193–199

    Article  PubMed  Google Scholar 

  • Campisi J, d’Adda di Fagagna F (2007) Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol 8:729–740

    Article  CAS  PubMed  Google Scholar 

  • Carroll JE, Cole SW, Seeman TE, Breen EC, Witarama T, Arevalo JMG, Ma J, Irwin MR (2016) Partial sleep deprivation activates the DNA damage response (DDR) and the senescence-associated secretory phenotype (SASP) in aged adult humans. Brain Behav Immun 51:223–229

    Article  CAS  PubMed  Google Scholar 

  • Chan V, Fenning A, Hoey A, Brown L (2011) Chronic β-adrenoceptor antagonist treatment controls cardiovascular remodeling in heart failure in the aging spontaneously hypertensive rat. J Cardiovasc Pharmacol 58:424–431

    Article  CAS  PubMed  Google Scholar 

  • Chan CT, Sobey CG, Lieu M, Ferens D, Kett MM, Diep H, Kim HA, Krishnan SM, Lewis CV, Salimova E, Tipping P, Vinh A, Samuel CS, Peter K, Guzik TJ, Kyaw TS, Toh BH, Bobik A, Drummond GR (2015) Obligatory role for B cells in the development of angiotensin II-dependent hypertension. Hypertension 66:1023–1033

    Article  CAS  PubMed  Google Scholar 

  • Chapman J, Fielder E, Passos JF (2019) Mitochondrial dysfunction and cell senescence: deciphering a complex relationship. FEBS Lett 593:1566–1579

    Article  CAS  PubMed  Google Scholar 

  • Chaudhary K, Malhotra K, Sowers J, Aroor A (2013) Uric acid - key ingredient in the recipe for cardiorenal metabolic syndrome. Cardiorenal Med 3:208–220

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen DD, Dong YG, Yuan H, Chen AF (2012) Endothelin 1 activation of endothelin A receptor/NADPH oxidase pathway and diminished antioxidants critically contribute to endothelial progenitor cell reduction and dysfunction in salt-sensitive hypertension. Hypertension 59:1037–1043

    Article  CAS  PubMed  Google Scholar 

  • Chen F, Chen B, Xiao FQ, Wu YT, Wang RH, Sun ZW, Fu GS, Mou Y, Tao W, Hu XS, Hu SJ (2014) Autophagy protects against senescence and apoptosis via the RAS-mitochondria in high-glucose-induced endothelial cells. Cell Physiol Biochem 33:1058–1074

    Article  CAS  PubMed  Google Scholar 

  • Chen C, Gao JL, Liu MY, Li SL, Xuan XC, Zhang XZ, Zhang XY, Wei YY, Zhen CL, Jin J, Shen X, Dong DL (2017) Mitochondrial fission inhibitors suppress endothelin-1-induced artery constriction. Cell Physiol Biochem 42:1802–1811

    Article  CAS  PubMed  Google Scholar 

  • Chen IC, Kuo CS, Wu CC, Tsai HY, Lin CP, Li SY, Chou RH, Huang PH, Chen JW, Lin SJ (2018) Chronic hyperuricemia impairs blood flow recovery in the ischemic hindlimb through suppression of endothelial progenitor cells. Oncotarget 9:9285–9298

    Article  PubMed  PubMed Central  Google Scholar 

  • Cheng G, Wang L, Dai M, Wei F, Xu D (2020) Shorter leukocyte telomere length coupled with lower expression of telomerase genes in patients with essential hypertension. Int J Med Sci 17:2180–2186

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cicalese SM, da Silva JF, Priviero F, Webb RC, Eguchi S, Tostes RC (2021) Vascular stress signaling in hypertension. Circ Res 128:969–992

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Coppé JP, Desprez PY, Krtolica A, Campisi J (2010) The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol 5:99–118

    Article  PubMed  PubMed Central  Google Scholar 

  • d’Adda di Fagagna F, Reaper PM, Clay-Farrace L, Fiegler H, Carr P, Von Zglinicki T, Saretzki G, Carter NP, Jackson SP (2003) A DNA damage checkpoint response in telomere-initiated senescence. Nature 426:194–198

    Article  CAS  PubMed  Google Scholar 

  • Dagher O, Mury P, Thorin-Trescases N, Noly PE, Thorin E, Carrier M (2021) Therapeutic potential of quercetin to alleviate endothelial dysfunction in age-related cardiovascular diseases. Front Cardiovasc Med 8:658400

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Daschil N, Kniewallner KM, Obermair GJ, Hutter-Paier B, Windisch M, Marksteiner J, Humpel C (2015) L-type calcium channel blockers and substance P induce angiogenesis of cortical vessels associated with beta-amyloid plaques in an Alzheimer mouse model. Neurobiol Aging 36:1333–1341

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • de Oliveira RM (2006) Klotho RNAi induces premature senescence of human cells via a p53/p21 dependent pathway. FEBS Lett 580:5753–5758

    Article  PubMed  Google Scholar 

  • de Cavanagh EM, Piotrkowski B, Basso N, Stella I, Inserra F, Ferder L, Fraga CG (2003) Enalapril and losartan attenuate mitochondrial dysfunction in aged rats. Faseb j 17:1096–1098

    Article  PubMed  Google Scholar 

  • De Meyer GR, Grootaert MO, Michiels CF, Kurdi A, Schrijvers DM, Martinet W (2015) Autophagy in vascular disease. Circ Res 116:468–479

    Article  PubMed  Google Scholar 

  • De Miguel C, Pelegrín P, Baroja-Mazo A, Cuevas S (2021) Emerging role of the inflammasome and pyroptosis in hypertension. Int J Mol Sci 22:1064

    Article  PubMed  PubMed Central  Google Scholar 

  • De Munck DG, Leloup AJA, De Meyer GRY, Martinet W, Fransen P (2020) Defective autophagy in vascular smooth muscle cells increases passive stiffness of the mouse aortic vessel wall. Pflugers Arch 472:1031–1040

    Article  PubMed  Google Scholar 

  • Demissie S, Levy D, Benjamin EJ, Cupples LA, Gardner JP, Herbert A, Kimura M, Larson MG, Meigs JB, Keaney JF, Aviv A (2006) Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study. Aging Cell 5:325–330

    Article  CAS  PubMed  Google Scholar 

  • Deng Y, Li S, Chen Z, Wang W, Geng B, Cai J (2021) Mdivi-1, a mitochondrial fission inhibitor, reduces angiotensin-II- induced hypertension by mediating VSMC phenotypic switch. Biomed Pharmacother 140:111689

    Article  CAS  PubMed  Google Scholar 

  • Dikalov S, Dikalova A (2022) Mitochondrial deacetylase Sirt3 in vascular dysfunction and hypertension. Curr Opin Nephrol Hypertens 31:151–156

    Article  CAS  PubMed  Google Scholar 

  • Dikalova AE, Itani HA, Nazarewicz RR, McMaster WG, Flynn CR, Uzhachenko R, Fessel JP, Gamboa JL, Harrison DG, Dikalov SI (2017) Sirt3 impairment and SOD2 hyperacetylation in vascular oxidative stress and hypertension. Circ Res 121:564–574

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dikalova AE, Pandey A, Xiao L, Arslanbaeva L, Sidorova T, Lopez MG, Billings FT 4th, Verdin E, Auwerx J, Harrison DG, Dikalov SI (2020) (2020) Mitochondrial deacetylase Sirt3 reduces vascular dysfunction and hypertension while Sirt3 depletion in essential hypertension is linked to vascular inflammation and oxidative stress. Circ Res 126(4):439–452

    Article  CAS  PubMed  Google Scholar 

  • DiNatale JC, Crowe-White KM (2022) Effects of resveratrol supplementation on nitric oxide-mediated vascular outcomes in hypertension: a systematic review. Nitric Oxide 129:74–81

    Article  CAS  PubMed  Google Scholar 

  • Dioni L, Hoxha M, Nordio F, Bonzini M, Tarantini L, Albetti B, Savarese A, Schwartz J, Bertazzi PA, Apostoli P, Hou L, Baccarelli A (2011) Effects of short-term exposure to inhalable particulate matter on telomere length, telomerase expression, and telomerase methylation in steel workers. Environ Health Perspect 119:622–627

    Article  CAS  PubMed  Google Scholar 

  • Docherty MH, O’Sullivan ED, Bonventre JV, Ferenbach DA (2019) Cellular senescence in the kidney. J Am Soc Nephrol 30:726–736

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donato AJ, Gano LB, Eskurza I, Silver AE, Gates PE, Jablonski K, Seals DR (2009) Vascular endothelial dysfunction with aging: endothelin-1 and endothelial nitric oxide synthase. Am J Physiol Heart Circ Physiol 297:H425-432

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Donnini S, Terzuoli E, Ziche M, Morbidelli L (2010) Sulfhydryl angiotensin-converting enzyme inhibitor promotes endothelial cell survival through nitric-oxide synthase, fibroblast growth factor-2, and telomerase cross-talk. J Pharmacol Exp Ther 332:776–784

    Article  CAS  PubMed  Google Scholar 

  • Dudinskaya E, Tkacheva O, Bazaeva E, Matchekhina L, Eruslanova K, Sharashkina N, Kotovskaya Y, Larina V (2022) Influence of moxonidine and bisoprolol on morphofunctional condition of arterial wall and telomerase activity in postmenopausal women with arterial hypertension and osteopenia. The results from a moscow randomized study. Cardiovasc Drugs Ther 36:1147–1155

    Article  CAS  PubMed  Google Scholar 

  • Durgan DJ, Ganesh BP, Cope JL, Ajami NJ, Phillips SC, Petrosino JF, Hollister EB, Bryan RM Jr (2016) Role of the gut microbiome in obstructive sleep apnea-induced hypertension. Hypertension 67:469–474

    Article  CAS  PubMed  Google Scholar 

  • Endo R, Bahrudin U, Notsu T, Tanno S, Onohara T, Yamaguchi S, Ikeda N, Surastri B, Nakayama Y, Ninomiya H, Shirayoshi Y, Inagaki Y, Yamamoto K, Yoshida A, Hisatome I (2016) Carvedilol suppresses apoptosis and ion channel remodelling of HL-1 cardiac myocytes expressing E334K cMyBPC. Drug Res (stuttg) 66:126–129

    CAS  PubMed  Google Scholar 

  • Erusalimsky JD, Skene C (2009) Mechanisms of endothelial senescence. Exp Physiol 94:299–304

    Article  CAS  PubMed  Google Scholar 

  • Everson F, Martens DS, Nawrot TS, Goswami N, Mthethwa M, Webster I, Mashele N, Charania S, Kamau F, De Boever P, Strijdom H (2020) Personal exposure to NO(2) and benzene in the Cape Town region of South Africa is associated with shorter leukocyte telomere length in women. Environ Res 182:108993

    Article  CAS  PubMed  Google Scholar 

  • Fan YY, Kohno M, Hitomi H, Kitada K, Fujisawa Y, Yatabe J, Yatabe M, Felder RA, Ohsaki H, Rafiq K, Sherajee SJ, Noma T, Nishiyama A, Nakano D (2011) Aldosterone/mineralocorticoid receptor stimulation induces cellular senescence in the kidney. Endocrinology 152:680–688

    Article  CAS  PubMed  Google Scholar 

  • Feng X, Wang L, Li Y (2011) Change of telomere length in angiotensin II-induced human glomerular mesangial cell senescence and the protective role of losartan. Mol Med Rep 4:255–260

    CAS  PubMed  Google Scholar 

  • Frezza C, Cipolat S, Martins de Brito O, Micaroni M, Beznoussenko GV, Rudka T, Bartoli D, Polishuck RS, Danial NN, De Strooper B, Scorrano L (2006) OPA1 controls apoptotic cristae remodeling independently from mitochondrial fusion. Cell 126:177–189

    Article  CAS  PubMed  Google Scholar 

  • Frudd K, Burgoyne T, Burgoyne JR (2018) Oxidation of Atg3 and Atg7 mediates inhibition of autophagy. Nat Commun 9:95

    Article  PubMed  PubMed Central  Google Scholar 

  • Fung MM, Peters K, Redline S, Ziegler MG, Ancoli-Israel S, Barrett-Connor E, Stone KL (2011) Decreased slow wave sleep increases risk of developing hypertension in elderly men. Hypertension 58:596–603

    Article  CAS  PubMed  Google Scholar 

  • Funovic P, Korda M, Kubant R, Barlag RE, Jacob RF, Mason RP, Malinski T (2008) Effect of beta-blockers on endothelial function during biological aging: a nanotechnological approach. J Cardiovasc Pharmacol 51:208–215

    Article  CAS  PubMed  Google Scholar 

  • Galla S, Chakraborty S, Mell B, Vijay-Kumar M, Joe B (2017) Microbiotal-host interactions and hypertension. Physiology (bethesda) 32:224–233

    CAS  PubMed  Google Scholar 

  • Gan L, Liu D, Liu J, Chen E, Chen C, Liu L, Hu H, Guan X, Ma W, Zhang Y, He Y, Liu B, Tang S, Jiang W, Xue J, Xin H (2021) CD38 deficiency alleviates Ang II-induced vascular remodeling by inhibiting small extracellular vesicle-mediated vascular smooth muscle cell senescence in mice. Signal Transduct Target Ther 6:223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao D, Zuo Z, Tian J, Ali Q, Lin Y, Lei H, Sun Z (2016) Activation of SIRT1 attenuates klotho deficiency-induced arterial stiffness and hypertension by enhancing AMP-activated protein kinase activity. Hypertension 68:1191–1199

    Article  CAS  PubMed  Google Scholar 

  • Gao J, Zhang K, Wang Y, Guo R, Liu H, Jia C, Sun X, Wu C, Wang W, Du J, Chen J (2020) A machine learning-driven study indicates emodin improves cardiac hypertrophy by modulation of mitochondrial SIRT3 signaling. Pharmacol Res 155:104739

    Article  CAS  PubMed  Google Scholar 

  • Gao P, Zou X, Sun X, Zhang C (2022) Cellular senescence in metabolic-associated kidney disease: an update. Cells 11:3443

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gardner SE, Humphry M, Bennett MR, Clarke MC (2015) Senescent vascular smooth muscle cells drive inflammation through an Interleukin-1α-dependent senescence-associated secretory phenotype. Arterioscler Thromb Vasc Biol 35:1963–1974

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gleason CE, Frindt G, Cheng CJ, Ng M, Kidwai A, Rashmi P, Lang F, Baum M, Palmer LG, Pearce D (2015) mTORC2 regulates renal tubule sodium uptake by promoting ENaC activity. J Clin Invest 125:117–128

    Article  PubMed  Google Scholar 

  • Grootaert MO, da Costa Martins PA, Bitsch N, Pintelon I, De Meyer GR, Martinet W, Schrijvers DM (2015) Defective autophagy in vascular smooth muscle cells accelerates senescence and promotes neointima formation and atherogenesis. Autophagy 11:2014–2032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C, Harrison DG (2007) Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 204:2449–2460

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hasan P, Saotome M, Ikoma T, Iguchi K, Kawasaki H, Iwashita T, Hayashi H, Maekawa Y (2018) Mitochondrial fission protein, dynamin-related protein 1, contributes to the promotion of hypertensive cardiac hypertrophy and fibrosis in Dahl-salt sensitive rats. J Mol Cell Cardiol 121:103–106

    Article  CAS  PubMed  Google Scholar 

  • Hayashi T, Yamaguchi T, Sakakibara Y, Taguchi K, Maeda M, Kuzuya M, Hattori Y (2014) eNOS-dependent antisenscence effect of a calcium channel blocker in human endothelial cells. PLoS ONE 9:e88391

    Article  PubMed  PubMed Central  Google Scholar 

  • Head T, Daunert S, Goldschmidt-Clermont PJ (2017) The aging risk and atherosclerosis: a fresh look at arterial homeostasis. Front Genet 8:216

    Article  PubMed  PubMed Central  Google Scholar 

  • Heiss C, Keymel S, Niesler U, Ziemann J, Kelm M, Kalka C (2005) Impaired progenitor cell activity in age-related endothelial dysfunction. J Am Coll Cardiol 45:1441–1448

    Article  CAS  PubMed  Google Scholar 

  • Holdt LM, Sass K, Gäbel G, Bergert H, Thiery J, Teupser D (2011) Expression of Chr9p21 genes CDKN2B (p15(INK4b)), CDKN2A (p16(INK4a), p14(ARF)) and MTAP in human atherosclerotic plaque. Atherosclerosis 214:264–270

    Article  CAS  PubMed  Google Scholar 

  • Hong N, Ye Z, Lin Y, Liu W, Xu N, Wang Y (2021) Agomelatine prevents angiotensin II-induced endothelial and mononuclear cell adhesion. Aging (albany NY) 13:18515–18526

    Article  CAS  PubMed  Google Scholar 

  • Hou L, Wang S, Dou C, Zhang X, Yu Y, Zheng Y, Avula U, Hoxha M, Díaz A, McCracken J, Barretta F, Marinelli B, Bertazzi PA, Schwartz J, Baccarelli AA (2012) Air pollution exposure and telomere length in highly exposed subjects in Beijing, China: a repeated-measure study. Environ Int 48:71–77

    Article  CAS  PubMed  Google Scholar 

  • Hu XQ, Zhang L (2022) Oxidative regulation of vascular Ca(v)1.2 channels triggers vascular dysfunction in hypertension-related disorders. Antioxidants (Basel) 11:2432

    Article  CAS  PubMed  Google Scholar 

  • Hu C, Zhang X, Teng T, Ma ZG, Tang QZ (2022) Cellular senescence in cardiovascular diseases: a systematic review. Aging Dis 13:103–128

    Article  PubMed  PubMed Central  Google Scholar 

  • Huang H, Liao D, Dong Y, Pu R (2020) Effect of quercetin supplementation on plasma lipid profiles, blood pressure, and glucose levels: a systematic review and meta-analysis. Nutr Rev 78:615–626

    Article  PubMed  Google Scholar 

  • Huang W, Hickson LJ, Eirin A, Kirkland JL, Lerman LO (2022) Cellular senescence: the good, the bad and the unknown. Nat Rev Nephrol 18:611–627

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hwang HJ, Kim N, Herman AB, Gorospe M, Lee JS (2022) Factors and pathways modulating endothelial cell senescence in vascular aging. Int J Mol Sci 23:10135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ikushima M, Rakugi H, Ishikawa K, Maekawa Y, Yamamoto K, Ohta J, Chihara Y, Kida I, Ogihara T (2006) Anti-apoptotic and anti-senescence effects of Klotho on vascular endothelial cells. Biochem Biophys Res Commun 339:827–832

    Article  CAS  PubMed  Google Scholar 

  • Jeong JJ, Kim KA, Jang SE, Woo JY, Han MJ, Kim DH (2015) Orally administrated Lactobacillus pentosus var. plantarum C29 ameliorates age-dependent colitis by inhibiting the nuclear factor-kappa B signaling pathway via the regulation of lipopolysaccharide production by gut microbiota. PLoS One 10:e0116533

    Article  PubMed  PubMed Central  Google Scholar 

  • Jia X, Zhang R, Guo J, Yue H, Liu Q, Guo L, Zhang Q (2020) Resveratrol supplementation prevents hypertension in hypertensive pregnant rats by increasing sodium excretion and serum nitric oxide level. Int J Hypertens 2020:4154010

    Article  PubMed  PubMed Central  Google Scholar 

  • Jiang GJ, Li BB, Fan TJ (2021) Timolol induces necroptosis, apoptosis and senescence concentration-dependently in rabbit Limbal stem cells in vitro. Life Sci 277:119453

    Article  CAS  PubMed  Google Scholar 

  • Jiao S, Zheng X, Yang X, Zhang J, Wang L (2012) Losartan inhibits STAT1 activation and protects human glomerular mesangial cells from angiotensin II induced premature senescence. Can J Physiol Pharmacol 90:89–98

    Article  CAS  PubMed  Google Scholar 

  • Jovanovski E, Bateman EA, Bhardwaj J, Fairgrieve C, Mucalo I, Jenkins AL, Vuksan V (2014) Effect of Rg3-enriched Korean red ginseng (Panax ginseng) on arterial stiffness and blood pressure in healthy individuals: a randomized controlled trial. J Am Soc Hypertens 8:537–541

    Article  CAS  PubMed  Google Scholar 

  • Jovanovski E, Lea Duvnjak S, Komishon A, Au-Yeung F, Zurbau A, Jenkins AL, Sung MK, Josse R, Vuksan V (2020) Vascular effects of combined enriched Korean Red ginseng (Panax Ginseng) and American ginseng (Panax Quinquefolius) administration in individuals with hypertension and type 2 diabetes: A randomized controlled trial. Complement Ther Med 49:102338

    Article  PubMed  Google Scholar 

  • Kanbay M, Onal EM, Afsar B, Dagel T, Yerlikaya A, Covic A, Vaziri ND (2018) The crosstalk of gut microbiota and chronic kidney disease: role of inflammation, proteinuria, hypertension, and diabetes mellitus. Int Urol Nephrol 50:1453–1466

    Article  PubMed  Google Scholar 

  • Kanbay M, Demiray A, Afsar B, Covic A, Tapoi L, Ureche C, Ortiz A (2021) Role of Klotho in the development of essential hypertension. Hypertension 77:740–750

    Article  CAS  PubMed  Google Scholar 

  • Kawarazaki W, Mizuno R, Nishimoto M, Ayuzawa N, Hirohama D, Ueda K, Kawakami-Mori F, Oba S, Marumo T, Fujita T (2020) Salt causes aging-associated hypertension via vascular Wnt5a under Klotho deficiency. J Clin Invest 130:4152–4166

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kayamori H, Shimizu I, Yoshida Y, Hayashi Y, Suda M, Ikegami R, Katsuumi G, Wakasugi T, Minamino T (2018) Amlodipine inhibits vascular cell senescence and protects against atherogenesis through the mechanism independent of calcium channel blockade. Int Heart J 59:607–613

    Article  CAS  PubMed  Google Scholar 

  • Kim EC, Kim JR (2019) Senotherapeutics: emerging strategy for healthy aging and age-related disease. BMB Rep 52:47–55

    Article  PubMed  PubMed Central  Google Scholar 

  • Kim JM, Heo HS, Choi YJ, Ye BH, Mi Ha Y, Seo AY, Yu BP, Leeuwenburgh C, Chung HY, Carter CS (2011) Inhibition of NF-κB-induced inflammatory responses by angiotensin II antagonists in aged rat kidney. Exp Gerontol 46:542–548

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kim SG, Sung JY, Kim JR, Choi HC (2020) Nifedipine-induced AMPK activation alleviates senescence by increasing autophagy and suppressing of Ca(2+) levels in vascular smooth muscle cells. Mech Ageing Dev 190:111314

    Article  CAS  PubMed  Google Scholar 

  • Kitagawa M, Sugiyama H, Morinaga H, Inoue T, Takiue K, Ogawa A, Yamanari T, Kikumoto Y, Uchida HA, Kitamura S, Maeshima Y, Nakamura K, Ito H, Makino H (2013) A decreased level of serum soluble Klotho is an independent biomarker associated with arterial stiffness in patients with chronic kidney disease. PLoS ONE 8:e56695

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kobayashi K, Imanishi T, Akasaka T (2006) Endothelial progenitor cell differentiation and senescence in an angiotensin II-infusion rat model. Hypertens Res 29:449–455

    Article  CAS  PubMed  Google Scholar 

  • Kohn FR, Kung AH (1995) Role of endotoxin in acute inflammation induced by gram-negative bacteria: specific inhibition of lipopolysaccharide-mediated responses with an amino-terminal fragment of bactericidal/permeability-increasing protein. Infect Immun 63:333–339

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kostov K (2021) The causal relationship between endothelin-1 and hypertension: focusing on endothelial dysfunction, arterial stiffness, vascular remodeling, and blood pressure regulation. Life (Basel) 11:986

    CAS  PubMed  Google Scholar 

  • Kumar R, Sharma A, Gupta M, Padwad Y, Sharma R (2020) Cell-free culture supernatant of probiotic lactobacillus fermentum protects against H(2)O(2)-induced premature senescence by suppressing ROS-Akt-mTOR axis in murine preadipocytes. Probiotics Antimicrob Proteins 12:563–576

    Article  CAS  PubMed  Google Scholar 

  • Kundu P, Lee HU, Garcia-Perez I, Tay EXY, Kim H, Faylon LE, Martin KA, Purbojati R, Drautz-Moses DI, Ghosh S, Nicholson JK, Schuster S, Holmes E, Pettersson S (2019) Neurogenesis and prolongevity signaling in young germ-free mice transplanted with the gut microbiota of old mice. Sci Transl Med. https://doi.org/10.1126/scitranslmed.aau4760

    Article  PubMed  PubMed Central  Google Scholar 

  • Kuo CS, Chen CY, Huang HL, Tsai HY, Chou RH, Wei JH, Huang PH, Lin SJ (2022) Melatonin improves ischemia-induced circulation recovery impairment in mice with streptozotocin-induced diabetes by improving the endothelial progenitor cells functioning. Int J Mol Sci 23:9839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kuro-o M, Matsumura Y, Aizawa H, Kawaguchi H, Suga T, Utsugi T, Ohyama Y, Kurabayashi M, Kaname T, Kume E, Iwasaki H, Iida A, Shiraki-Iida T, Nishikawa S, Nagai R, Nabeshima YI (1997) Mutation of the mouse klotho gene leads to a syndrome resembling ageing. Nature 390:45–51

    Article  CAS  PubMed  Google Scholar 

  • Lahera V, de Las Heras N, López-Farré A, Manucha W, Ferder L (2017) Role of mitochondrial dysfunction in hypertension and obesity. Curr Hypertens Rep 19:11

    Article  PubMed  Google Scholar 

  • Lai SR, Cunningham AP, Huynh VQ, Andrews LG, Tollefsbol TO (2007) Evidence of extra-telomeric effects of hTERT and its regulation involving a feedback loop. Exp Cell Res 313:322–330

    Article  CAS  PubMed  Google Scholar 

  • LaRocca TJ, Henson GD, Thorburn A, Sindler AL, Pierce GL, Seals DR (2012) Translational evidence that impaired autophagy contributes to arterial ageing. J Physiol 590:3305–3316

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lee J, Yoo JH, Kim HS, Cho YK, Lee Y, Lee WJ, Park JY, Jung CH (2021) C1q/TNF-related protein-9 attenuates palmitic acid-induced endothelial cell senescence via increasing autophagy. Mol Cell Endocrinol 521:111114

    Article  CAS  PubMed  Google Scholar 

  • Li HL, Kang YM, Yu L, Xu HY, Zhao H (2009a) Melatonin reduces blood pressure in rats with stress-induced hypertension via GABAA receptors. Clin Exp Pharmacol Physiol 36:436–440

    Article  CAS  PubMed  Google Scholar 

  • Li QX, Xiong ZY, Hu BP, Tian ZJ, Zhang HF, Gou WY, Wang HC, Gao F, Zhang QJ (2009b) Aging-associated insulin resistance predisposes to hypertension and its reversal by exercise: the role of vascular vasorelaxation to insulin. Basic Res Cardiol 104:269–284

    Article  CAS  PubMed  Google Scholar 

  • Li ZP, Xin RJ, Yang H, Jiang GJ, Deng YP, Li DJ, Shen FM (2016) Diazoxide accelerates wound healing by improving EPC function. Front Biosci (landmark Ed) 21:1039–1051

    Article  CAS  PubMed  Google Scholar 

  • Li J, Zhao F, Wang Y, Chen J, Tao J, Tian G, Wu S, Liu W, Cui Q, Geng B, Zhang W, Weldon R, Auguste K, Yang L, Liu X, Chen L, Yang X, Zhu B, Cai J (2017) Gut microbiota dysbiosis contributes to the development of hypertension. Microbiome 5:14

    Article  PubMed  PubMed Central  Google Scholar 

  • Li Q, Chen C, Chen X, Han M, Li J (2018) Dexmedetomidine attenuates renal fibrosis via α2-adrenergic receptor-dependent inhibition of cellular senescence after renal ischemia/reperfusion. Life Sci 207:1–8

    Article  CAS  PubMed  Google Scholar 

  • Li C, Lin L, Zhang L, Xu R, Chen X, Ji J, Li Y (2021) Long noncoding RNA p21 enhances autophagy to alleviate endothelial progenitor cells damage and promote endothelial repair in hypertension through SESN2/AMPK/TSC2 pathway. Pharmacol Res 173:105920

    Article  CAS  PubMed  Google Scholar 

  • Li Q, Huang K, Ma T, Lu S, Tang S, Wu M, Yang H, Zhong J (2022) Metoprolol protects against arginine vasopressin-induced cellular senescence in H9C2 cardiomyocytes by regulating the Sirt1/p53/p21 axis. Cardiovasc Toxicol 22:99–107

    Article  CAS  PubMed  Google Scholar 

  • Lim K, Lu TS, Molostvov G, Lee C, Lam FT, Zehnder D, Hsiao LL (2012) Vascular Klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 125:2243–2255

    Article  CAS  PubMed  Google Scholar 

  • Lin Y, Chen J, Sun Z (2016) Antiaging gene klotho deficiency promoted high-fat diet-induced arterial stiffening via inactivation of AMP-activated protein kinase. Hypertension 67:564–573

    Article  CAS  PubMed  Google Scholar 

  • Linz W, Heitsch H, Schölkens BA, Wiemer G (2000) Long-term angiotensin II type 1 receptor blockade with fonsartan doubles lifespan of hypertensive rats. Hypertension 35:908–913

    Article  CAS  PubMed  Google Scholar 

  • Liu C, Yang Q, Hwang SJ, Sun F, Johnson AD, Shirihai OS, Vasan RS, Levy D, Schwartz F (2012) Association of genetic variation in the mitochondrial genome with blood pressure and metabolic traits. Hypertension 60:949–956

    Article  CAS  PubMed  Google Scholar 

  • Liu W, Lin H, Mao Z, Zhang L, Bao K, Jiang B, Xia C, Li W, Hu Z, Li J (2020) Verapamil extends lifespan in Caenorhabditis elegans by inhibiting calcineurin activity and promoting autophagy. Aging (albany NY) 12:5300–5317

    Article  CAS  PubMed  Google Scholar 

  • Maier JA, Voulalas P, Roeder D, Maciag T (1990) Extension of the life-span of human endothelial cells by an interleukin-1 alpha antisense oligomer. Science 249:1570–1574

    Article  CAS  PubMed  Google Scholar 

  • Mameli E, Martello A, Caporali A (2022) Autophagy at the interface of endothelial cell homeostasis and vascular disease. Febs j 289:2976–2991

    Article  CAS  PubMed  Google Scholar 

  • Mashhadi FD, Salari R, Ghorbanzadeh H (2020) The effect of resveratrol dose and duration of treatment on blood pressure in patients with cardiovascular disorders: a systematic review. Curr Drug Discov Technol 17:325–331

    Article  CAS  PubMed  Google Scholar 

  • McCarthy CG, Wenceslau CF, Goulopoulou S, Ogbi S, Baban B, Sullivan JC, Matsumoto T, Webb RC (2015) Circulating mitochondrial DNA and Toll-like receptor 9 are associated with vascular dysfunction in spontaneously hypertensive rats. Cardiovasc Res 107:119–130

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCarthy CG, Wenceslau CF, Webb RC, Joe B (2019) Novel contributors and mechanisms of cellular senescence in hypertension-associated premature vascular aging. Am J Hypertens 32:709–719

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • McCracken J, Baccarelli A, Hoxha M, Dioni L, Melly S, Coull B, Suh H, Vokonas P, Schwartz J (2010) Annual ambient black carbon associated with shorter telomeres in elderly men: veterans affairs normative aging study. Environ Health Perspect 118:1564–1570

    Article  PubMed  PubMed Central  Google Scholar 

  • Min LJ, Mogi M, Iwanami J, Li JM, Sakata A, Fujita T, Tsukuda K, Iwai M, Horiuchi M (2007) Cross-talk between aldosterone and angiotensin II in vascular smooth muscle cell senescence. Cardiovasc Res 76:506–516

    Article  CAS  PubMed  Google Scholar 

  • Min LJ, Mogi M, Iwanami J, Li JM, Sakata A, Fujita T, Tsukuda K, Iwai M, Horiuchi M (2008) Angiotensin II type 2 receptor deletion enhances vascular senescence by methyl methanesulfonate sensitive 2 inhibition. Hypertension 51:1339–1344

    Article  CAS  PubMed  Google Scholar 

  • Min LJ, Mogi M, Iwanami J, Jing F, Tsukuda K, Ohshima K, Horiuchi M (2012) Angiotensin II type 2 receptor-interacting protein prevents vascular senescence. J Am Soc Hypertens 6:179–184

    Article  CAS  PubMed  Google Scholar 

  • Mogi M (2020) Effect of renin-angiotensin system on senescence. Geriatr Gerontol Int 20:520–525

    Article  PubMed  Google Scholar 

  • Morgan RG, Ives SJ, Lesniewski LA, Cawthon RM, Andtbacka RH, Noyes RD, Richardson RS, Donato AJ (2013) Age-related telomere uncapping is associated with cellular senescence and inflammation independent of telomere shortening in human arteries. Am J Physiol Heart Circ Physiol 305:H251-258

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan RG, Ives SJ, Walker AE, Cawthon RM, Andtbacka RH, Noyes D, Lesniewski LA, Richardson RS, Donato AJ (2014) Role of arterial telomere dysfunction in hypertension: relative contributions of telomere shortening and telomere uncapping. J Hypertens 32:1293–1299

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan RG, Donato AJ, Walker AE (2018) Telomere uncapping and vascular aging. Am J Physiol Heart Circ Physiol 315:H1-h5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Morgan RG, Walker AE, Trott DW, Machin DR, Henson GD, Reihl KD, Cawthon RM, Denchi EL, Liu Y, Bloom SI, Phuong TT, Richardson RS, Lesniewski LA, Donato AJ (2019) Induced Trf2 deletion leads to aging vascular phenotype in mice associated with arterial telomere uncapping, senescence signaling, and oxidative stress. J Mol Cell Cardiol 127:74–82

    Article  CAS  PubMed  Google Scholar 

  • Moser M, Frishman W (1998) Results of therapy with carvedilol, a beta-blocker vasodilator with antioxidant properties, in hypertensive patients. Am J Hypertens 11:15s–22s

    Article  CAS  PubMed  Google Scholar 

  • Mucalo I, Jovanovski E, Rahelić D, Božikov V, Romić Z, Vuksan V (2013) Effect of American ginseng (Panax quinquefolius L.) on arterial stiffness in subjects with type-2 diabetes and concomitant hypertension. J Ethnopharmacol 150:148–153

    Article  CAS  PubMed  Google Scholar 

  • Mukai Y, Shimokawa H, Higashi M, Morikawa K, Matoba T, Hiroki J, Kunihiro I, Talukder HM, Takeshita A (2002) Inhibition of renin-angiotensin system ameliorates endothelial dysfunction associated with aging in rats. Arterioscler Thromb Vasc Biol 22:1445–1450

    Article  CAS  PubMed  Google Scholar 

  • Nishimura A, Shimauchi T, Tanaka T, Shimoda K, Toyama T, Kitajima N, Ishikawa T, Shindo N, Numaga-Tomita T, Yasuda S, Sato Y, Kuwahara K, Kumagai Y, Akaike T, Ide T, Ojida A, Mori Y, Nishida M (2018) Hypoxia-induced interaction of filamin with Drp1 causes mitochondrial hyperfission-associated myocardial senescence. Sci Signal. https://doi.org/10.1126/scisignal.aat5185

    Article  PubMed  Google Scholar 

  • Norlander AE, Madhur MS, Harrison DG (2018) The immunology of hypertension. J Exp Med 215:21–33

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nosalski R, Guzik TJ (2017) Perivascular adipose tissue inflammation in vascular disease. Br J Pharmacol 174:3496–3513

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Olichon A, Baricault L, Gas N, Guillou E, Valette A, Belenguer P, Lenaers G (2003) Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem 278:7743–7746

    Article  CAS  PubMed  Google Scholar 

  • Pan X, Wu B, Fan X, Xu G, Ou C, Chen M (2021) YAP accelerates vascular senescence via blocking autophagic flux and activating mTOR. J Cell Mol Med 25:170–183

    Article  CAS  PubMed  Google Scholar 

  • Park MY, Herrmann SM, Saad A, Eirin A, Tang H, Lerman A, Textor SC, Lerman LO (2015) Biomarkers of kidney injury and klotho in patients with atherosclerotic renovascular disease. Clin J Am Soc Nephrol 10:443–451

    Article  PubMed  Google Scholar 

  • Perrault SD, Hornsby PJ, Betts DH (2005) Global gene expression response to telomerase in bovine adrenocortical cells. Biochem Biophys Res Commun 335:925–936

    Article  CAS  PubMed  Google Scholar 

  • Prado AF, Batista RIM, Tanus-Santos JE, Gerlach RF (2021) Matrix metalloproteinases and arterial hypertension: role of oxidative stress and nitric oxide in vascular functional and structural alterations. Biomolecules 11:585

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Puddu P, Puddu GM, Cravero E, Vizioli L, Muscari A (2012) Relationships among hyperuricemia, endothelial dysfunction and cardiovascular disease: molecular mechanisms and clinical implications. J Cardiol 59:235–242

    Article  PubMed  Google Scholar 

  • Pyo JO, Yoo SM, Ahn HH, Nah J, Hong SH, Kam TI, Jung S, Jung YK (2013) Overexpression of Atg5 in mice activates autophagy and extends lifespan. Nat Commun 4:2300

    Article  PubMed  Google Scholar 

  • Radak Z, Torma F, Berkes I, Goto S, Mimura T, Posa A, Balogh L, Boldogh I, Suzuki K, Higuchi M, Koltai E (2019) Exercise effects on physiological function during aging. Free Radic Biol Med 132:33–41

    Article  CAS  PubMed  Google Scholar 

  • Rahbarghazi R, Farhoudi M, Rahmani-Youshanlouei H, Hassanpour M, Rahbarghazi A, Rezaie J, Ahmadi M (2022) Putative effect of melatonin on cardiomyocyte senescence in mice with type 1 diabetes mellitus. J Diabetes Metab Disord 21:353–359

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Rhee MY, Kim YS, Bae JH, Nah DY, Kim YK, Lee MM, Kim HY (2011) Effect of Korean red ginseng on arterial stiffness in subjects with hypertension. J Altern Complement Med 17:45–49

    Article  PubMed  Google Scholar 

  • Robert P, Nguyen PMC, Richard A, Grenier C, Chevrollier A, Munier M, Grimaud L, Proux C, Champin T, Lelièvre E, Sarzi E, Vessières E, Henni S, Prunier D, Reynier P, Lenaers G, Fassot C, Henrion D, Loufrani L (2021) Protective role of the mitochondrial fusion protein OPA1 in hypertension. Faseb j 35:e21678

    Article  CAS  PubMed  Google Scholar 

  • Rodella LF, Favero G, Rossini C, Foglio E, Bonomini F, Reiter RJ, Rezzani R (2013) Aging and vascular dysfunction: beneficial melatonin effects. Age (dordr) 35:103–115

    Article  CAS  PubMed  Google Scholar 

  • Romero A, San Hipólito-Luengo Á, Villalobos LA, Vallejo S, Valencia I, Michalska P, Pajuelo-Lozano N, Sánchez-Pérez I, León R, Bartha JL, Sanz MJ, Erusalimsky JD, Sánchez-Ferrer CF, Romacho T, Peiró C (2019) The angiotensin-(1–7)/Mas receptor axis protects from endothelial cell senescence via klotho and Nrf2 activation. Aging Cell 18:e12913

    Article  PubMed  PubMed Central  Google Scholar 

  • Rubio-Ruiz ME, Pérez-Torres I, Soto ME, Pastelín G, Guarner-Lans V (2014) Aging in blood vessels. medicinal agents FOR systemic arterial hypertension in the elderly. Ageing Res Rev 18:132–147

    Article  CAS  PubMed  Google Scholar 

  • Saito Y, Nakamura T, Ohyama Y, Suzuki T, Iida A, Shiraki-Iida T, Kuro-o M, Nabeshima Y, Kurabayashi M, Nagai R (2000) In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. Biochem Biophys Res Commun 276:767–772

    Article  CAS  PubMed  Google Scholar 

  • Salama R, Sadaie M, Hoare M, Narita M (2014) Cellular senescence and its effector programs. Genes Dev 28:99–114

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Santelli A, Sun IO, Eirin A, Abumoawad AM, Woollard JR, Lerman A, Textor SC, Puranik AS, Lerman LO (2019) Senescent kidney cells in hypertensive patients release urinary extracellular vesicles. J Am Heart Assoc 8:e012584

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scaife PJ, Simpson A, Kurlak LO, Briggs LV, Gardner DS, Broughton Pipkin F, Jones CJP, Mistry HD (2021) Increased placental cell senescence and oxidative stress in women with pre-eclampsia and normotensive post-term pregnancies. Int J Mol Sci 22:7295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Scalera F, Martens-Lobenhoffer J, Bukowska A, Lendeckel U, Täger M, Bode-Böger SM (2008) Effect of telmisartan on nitric oxide–asymmetrical dimethylarginine system: role of angiotensin II type 1 receptor gamma and peroxisome proliferator activated receptor gamma signaling during endothelial aging. Hypertension 51:696–703

    Article  CAS  PubMed  Google Scholar 

  • Schafer MJ, Miller JD, LeBrasseur NK (2017) Cellular senescence: implications for metabolic disease. Mol Cell Endocrinol 455:93–102

    Article  CAS  PubMed  Google Scholar 

  • Schulman IH, Zhou MS, Jaimes EA, Raij L (2007) Dissociation between metabolic and vascular insulin resistance in aging. Am J Physiol Heart Circ Physiol 293:H853-859

    Article  CAS  PubMed  Google Scholar 

  • Serban MC, Sahebkar A, Zanchetti A, Mikhailidis DP, Howard G, Antal D, Andrica F, Ahmed A, Aronow WS, Muntner P, Lip GY, Graham I, Wong N, Rysz J, Banach M (2016) Effects of quercetin on blood pressure: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc. https://doi.org/10.1161/JAHA.115.002713

    Article  PubMed  PubMed Central  Google Scholar 

  • Serna-Salas SA, Arroyave-Ospina JC, Zhang M, Damba T, Buist-Homan M, Muñoz-Ortega MH, Ventura-Juárez J, Moshage H (2022) α-1 Adrenergic receptor antagonist doxazosin reverses hepatic stellate cells activation via induction of senescence. Mech Ageing Dev 201:111617

    Article  CAS  PubMed  Google Scholar 

  • Shan M, Yang X, Ezzati M, Chaturvedi N, Coady E, Hughes A, Shi Y, Yang M, Zhang Y, Baumgartner J (2014) A feasibility study of the association of exposure to biomass smoke with vascular function, inflammation, and cellular aging. Environ Res 135:165–172

    Article  CAS  PubMed  Google Scholar 

  • Sharma R (2022) Emerging interrelationship between the gut microbiome and cellular senescence in the context of aging and disease: perspectives and therapeutic opportunities. Probiotics Antimicrob Proteins 14:648–663

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sharma K, Lee HH, Gong DS, Park SH, Yi E, Schini-Kerth V, Oak MH (2019) Fine air pollution particles induce endothelial senescence via redox-sensitive activation of local angiotensin system. Environ Pollut 252:317–329

    Article  CAS  PubMed  Google Scholar 

  • Simão VA, Ferder L, Manucha W, Chuffa LGA (2022) Epigenetic mechanisms involved in inflammaging-associated hypertension. Curr Hypertens Rep 24:547–562

    Article  PubMed  Google Scholar 

  • Simko F, Reiter RJ, Pechanova O, Paulis L (2013) Experimental models of melatonin-deficient hypertension. Front Biosci (landmark Ed) 18:616–625

    Article  CAS  PubMed  Google Scholar 

  • Sobko T, Huang L, Midtvedt T, Norin E, Gustafsson LE, Norman M, Jansson EA, Lundberg JO (2006) Generation of NO by probiotic bacteria in the gastrointestinal tract. Free Radic Biol Med 41:985–991

    Article  CAS  PubMed  Google Scholar 

  • Sohn HJ, Yoo KH, Jang GY, Lee JH, Choi BM, Lee JH, Bae IS, Yim HE, Son CS, Lee JW (2010) Aldosterone modulates cell proliferation and apoptosis in the neonatal rat heart. J Korean Med Sci 25:1296–1304

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Solak Y, Afsar B, Vaziri ND, Aslan G, Yalcin CE, Covic A, Kanbay M (2016) Hypertension as an autoimmune and inflammatory disease. Hypertens Res 39:567–573

    Article  CAS  PubMed  Google Scholar 

  • Sosnowska B, Mazidi M, Penson P, Gluba-Brzózka A, Rysz J, Banach M (2017) The sirtuin family members SIRT1, SIRT3 and SIRT6: Their role in vascular biology and atherogenesis. Atherosclerosis 265:275–282

    Article  CAS  PubMed  Google Scholar 

  • Speer H, McKune AJ (2021) Aging under pressure: the roles of reactive oxygen and nitrogen species (RONS) production and aging skeletal muscle in endothelial function and hypertension-from biological processes to potential interventions. Antioxidants (Basel) 10:1247

    Article  CAS  PubMed  Google Scholar 

  • Spitler KM, Webb RC (2014) Endoplasmic reticulum stress contributes to aortic stiffening via proapoptotic and fibrotic signaling mechanisms. Hypertension 63:e40-45

    Article  CAS  PubMed  Google Scholar 

  • Stavro PM, Woo M, Heim TF, Leiter LA, Vuksan V (2005) North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension. Hypertension 46:406–411

    Article  CAS  PubMed  Google Scholar 

  • Su H, Gu Y, Li F, Wang Q, Huang B, Jin X, Ning G, Sun F (2013) The PI3K/AKT/mTOR signaling pathway is overactivated in primary aldosteronism. PLoS ONE 8:e62399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Sung JY, Lee KY, Kim JR, Choi HC (2018) Interaction between mTOR pathway inhibition and autophagy induction attenuates adriamycin-induced vascular smooth muscle cell senescence through decreased expressions of p53/p21/p16. Exp Gerontol 109:51–58

    Article  CAS  PubMed  Google Scholar 

  • Taddei S, Salvetti A (2002) Endothelial dysfunction in essential hypertension: clinical implications. J Hypertens 20:1671–1674

    Article  CAS  PubMed  Google Scholar 

  • Takenaka T, Inoue T, Miyazaki T, Kobori H, Nishiyama A, Ishii N, Hayashi M, Suzuki H (2018) Klotho ameliorates medullary fibrosis and pressure natriuresis in hypertensive rat kidneys. Hypertension 72:1151–1159

    Article  CAS  PubMed  Google Scholar 

  • Tamtaji OR, Milajerdi A, Dadgostar E, Kolahdooz F, Chamani M, Amirani E, Mirzaei H, Asemi Z (2019) The effects of quercetin supplementation on blood pressures and endothelial function among patients with metabolic syndrome and related disorders: a systematic review and meta-analysis of randomized controlled trials. Curr Pharm Des 25:1372–1384

    Article  CAS  PubMed  Google Scholar 

  • Tanase DM, Apostol AG, Costea CF, Tarniceriu CC, Tudorancea I, Maranduca MA, Floria M, Serban IL (2022) Oxidative stress in arterial hypertension (HTN): the nuclear factor erythroid factor 2-related factor 2 (Nrf2) pathway implications and future perspectives. Pharmaceutics 14:534

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tatar M, Bartke A, Antebi A (2003) The endocrine regulation of aging by insulin-like signals. Science 299:1346–1351

    Article  CAS  PubMed  Google Scholar 

  • Tehrani AY, White Z, Tung LW, Zhao RRY, Milad N, Seidman MA, Sauge E, Theret M, Rossi FMV, Esfandiarei M, van Breemen C, Bernatchez P (2022) Pleiotropic activation of endothelial function by angiotensin II receptor blockers is crucial to their protective anti-vascular remodeling effects. Sci Rep 12:9771

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Tian Z, Liang M (2021) Renal Metabolism and Hypertension. Nat Commun 12:963

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Topcu SO, Erbagci A, Erturhan S, Yagci F, Ucak R (2008) Verapamil attenuates renal tubular apoptosis in response to partial unilateral ureteral obstruction. Urol Int 80:84–89

    Article  CAS  PubMed  Google Scholar 

  • Umemura T, Soga J, Hidaka T, Takemoto H, Nakamura S, Jitsuiki D, Nishioka K, Goto C, Teragawa H, Yoshizumi M, Chayama K, Higashi Y (2008) Aging and hypertension are independent risk factors for reduced number of circulating endothelial progenitor cells. Am J Hypertens 21:1203–1209

    Article  CAS  PubMed  Google Scholar 

  • Vallée A, Lévy BL, Blacher J (2018) Interplay between the renin-angiotensin system, the canonical WNT/β-catenin pathway and PPARγ in hypertension. Curr Hypertens Rep 20:62

    Article  PubMed  Google Scholar 

  • van Zonneveld AJ, Rabelink TJ (2006) Endothelial progenitor cells: biology and therapeutic potential in hypertension. Curr Opin Nephrol Hypertens 15:167–172

    Article  PubMed  Google Scholar 

  • Vasa M, Fichtlscherer S, Aicher A, Adler K, Urbich C, Martin H, Zeiher AM, Dimmeler S (2001) Number and migratory activity of circulating endothelial progenitor cells inversely correlate with risk factors for coronary artery disease. Circ Res 89:E1-7

    Article  CAS  PubMed  Google Scholar 

  • Venkatachalam G, Surana U, Clément MV (2017) Replication stress-induced endogenous DNA damage drives cellular senescence induced by a sub-lethal oxidative stress. Nucleic Acids Res 45:10564–10582

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Sun Z (2009) Current understanding of klotho. Ageing Res Rev 8:43–51

    Article  PubMed  Google Scholar 

  • Wang HL, Xu Q, Wang Z, Zhang YH, Si LY, Li XJ, Yang QH, Xiao H (2010) A potential regulatory single nucleotide polymorphism in the promoter of the Klotho gene may be associated with essential hypertension in the Chinese Han population. Clin Chim Acta 411:386–390

    Article  CAS  PubMed  Google Scholar 

  • Wang S, Li R, Fettermann A, Li Z, Qian Y, Liu Y, Wang X, Zhou A, Mo JQ, Yang L, Jiang P, Taschner A, Rossmanith W, Guan MX (2011) Maternally inherited essential hypertension is associated with the novel 4263A>G mutation in the mitochondrial tRNAIle gene in a large Han Chinese family. Circ Res 108:862–870

    Article  CAS  PubMed  Google Scholar 

  • Wei W, Ji S (2018) Cellular senescence: Molecular mechanisms and pathogenicity. J Cell Physiol 233:9121–9135

    Article  CAS  PubMed  Google Scholar 

  • Wenzel P, Knorr M, Kossmann S, Stratmann J, Hausding M, Schuhmacher S, Karbach SH, Schwenk M, Yogev N, Schulz E, Oelze M, Grabbe S, Jonuleit H, Becker C, Daiber A, Waisman A, Münzel T (2011) Lysozyme M-positive monocytes mediate angiotensin II-induced arterial hypertension and vascular dysfunction. Circulation 124:1370–1381

    Article  CAS  PubMed  Google Scholar 

  • Westhoff JH, Hilgers KF, Steinbach MP, Hartner A, Klanke B, Amann K, Melk A (2008) Hypertension induces somatic cellular senescence in rats and humans by induction of cell cycle inhibitor p16INK4a. Hypertension 52:123–129

    Article  CAS  PubMed  Google Scholar 

  • Wilmanski T, Diener C, Rappaport N, Patwardhan S, Wiedrick J, Lapidus J, Earls JC, Zimmer A, Glusman G, Robinson M, Yurkovich JT, Kado DM, Cauley JA, Zmuda J, Lane NE, Magis AT, Lovejoy JC, Hood L, Gibbons SM, Orwoll ES, Price ND (2021) Gut microbiome pattern reflects healthy ageing and predicts survival in humans. Nat Metab 3:274–286

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu YH, Zhou JN, Balesar R, Unmehopa U, Bao A, Jockers R, Van Heerikhuize J, Swaab DF (2006) Distribution of MT1 melatonin receptor immunoreactivity in the human hypothalamus and pituitary gland: colocalization of MT1 with vasopressin, oxytocin, and corticotropin-releasing hormone. J Comp Neurol 499:897–910

    Article  CAS  PubMed  Google Scholar 

  • Wu VC, Lo SC, Chen YL, Huang PH, Tsai CT, Liang CJ, Kuo CC, Kuo YS, Lee BC, Wu EL, Lin YH, Sun YY, Lin SL, Chen JW, Lin SJ, Wu KD (2011) Endothelial progenitor cells in primary aldosteronism: a biomarker of severity for aldosterone vasculopathy and prognosis. J Clin Endocrinol Metab 96:3175–3183

    Article  CAS  PubMed  Google Scholar 

  • Xie Y, Lou D, Zhang D (2021) Melatonin alleviates age-associated endothelial injury of atherosclerosis via regulating telomere function. J Inflamm Res 14:6799–6812

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xu XJ, Zhao WB, Feng SB, Sun C, Chen Q, Ni B, Hu HY (2017) Celastrol alleviates angiotensin II-mediated vascular smooth muscle cell senescence via induction of autophagy. Mol Med Rep 16:7657–7664

    Article  CAS  PubMed  Google Scholar 

  • Yamagishi S, Takeuchi M (2004) Nifedipine inhibits gene expression of receptor for advanced glycation end products (RAGE) in endothelial cells by suppressing reactive oxygen species generation. Drugs Exp Clin Res 30:169–175

    CAS  PubMed  Google Scholar 

  • Yamagishi S, Kikuchi S, Takenaka K, Takeuchi M (2005) Blockade by nifedipine of advanced glycation end product-induced CD40-CD40 ligand interaction in endothelial cells. Drugs Exp Clin Res 31:221–226

    CAS  PubMed  Google Scholar 

  • Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, Miyoshi M, Ogawa Y, Castrillon DH, Rosenblatt KP, Kuro-o M (2005) Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 280:38029–38034

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Huang X, Jiang H, Zhang Y, Liu H, Qin C, Eisner GM, Jose PA, Rudolph L, Ju Z (2009) Short telomeres and prognosis of hypertension in a chinese population. Hypertension 53:639–645

    Article  CAS  PubMed  Google Scholar 

  • Yang T, Santisteban MM, Rodriguez V, Li E, Ahmari N, Carvajal JM, Zadeh M, Gong M, Qi Y, Zubcevic J, Sahay B, Pepine CJ, Raizada MK, Mohamadzadeh M (2015) Gut dysbiosis is linked to hypertension. Hypertension 65:1331–1340

    Article  CAS  PubMed  Google Scholar 

  • Yang Z, Zhan YW, Huang YY, Huang W, Zhan F, Lin SD (2020) Regulation of epithelial mesenchymal transition by the renin-angiotensin system: a role for klotho in renal tubular epithelial cells. J Biol Regul Homeost Agents 34:57–67

    CAS  PubMed  Google Scholar 

  • Yao EH, Fukuda N, Matsumoto T, Katakawa M, Yamamoto C, Han Y, Ueno T, Kobayashi N, Matsumoto K (2008) Effects of the antioxidative beta-blocker celiprolol on endothelial progenitor cells in hypertensive rats. Am J Hypertens 21:1062–1068

    Article  CAS  PubMed  Google Scholar 

  • Yen WL, Klionsky DJ (2008) How to live long and prosper: autophagy, mitochondria, and aging. Physiology (bethesda) 23:248–262

    CAS  PubMed  Google Scholar 

  • Yi W, Chen F, Zhang H, Tang P, Yuan M, Wen J, Wang S, Cai Z (2022) Role of angiotensin II in aging. Front Aging Neurosci 14:1002138

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yoo KH, Yim HE, Bae ES (2020) Angiotensin inhibition and cellular senescence in the developing rat kidney. Exp Mol Pathol 117:104551

    Article  CAS  PubMed  Google Scholar 

  • Yoshimoto S, Loo TM, Atarashi K, Kanda H, Sato S, Oyadomari S, Iwakura Y, Oshima K, Morita H, Hattori M, Honda K, Ishikawa Y, Hara E, Ohtani N (2013) Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome. Nature 499:97–101

    Article  CAS  PubMed  Google Scholar 

  • Youn JC, Yu HT, Lim BJ, Koh MJ, Lee J, Chang DY, Choi YS, Lee SH, Kang SM, Jang Y, Yoo OJ, Shin EC, Park S (2013) Immunosenescent CD8+ T cells and C-X-C chemokine receptor type 3 chemokines are increased in human hypertension. Hypertension 62:126–133

    Article  CAS  PubMed  Google Scholar 

  • Yu X, Li X, Jiang G, Wang X, Chang HC, Hsu WH, Li Q (2013) Isradipine prevents rotenone-induced intracellular calcium rise that accelerates senescence in human neuroblastoma SH-SY5Y cells. Neuroscience 246:243–253

    Article  CAS  PubMed  Google Scholar 

  • Yu J, Liu H, He S, Li P, Ma C, Ping F, Zhang H, Li W, Sun Q, Ma M, Liu Y, Lv L, Xu L, Li Y (2019) Negative association of serum URIC acid with peripheral blood cellular aging markers. J Nutr Health Aging 23:547–551

    Article  CAS  PubMed  Google Scholar 

  • Zhou Z, Peng J, Wang CJ, Li D, Li TT, Hu CP, Chen XP, Li YJ (2010) Accelerated senescence of endothelial progenitor cells in hypertension is related to the reduction of calcitonin gene-related peptide. J Hypertens 28:931–939

    Article  CAS  PubMed  Google Scholar 

  • Zhou L, Mo H, Miao J, Zhou D, Tan RJ, Hou FF, Liu Y (2015) Klotho ameliorates kidney injury and fibrosis and normalizes blood pressure by targeting the renin-angiotensin system. Am J Pathol 185:3211–3223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhou Y, Wan X, Seidel K, Zhang M, Goodman JB, Seta F, Hamburg N, Han J (2021) Aging and hypercholesterolemia differentially affect the unfolded protein response in the vasculature of Apoe(-/-) mice. J Am Heart Assoc 10:e020441

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zu Y, Liu L, Lee MY, Xu C, Liang Y, Man RY, Vanhoutte PM, Wang Y (2010) SIRT1 promotes proliferation and prevents senescence through targeting LKB1 in primary porcine aortic endothelial cells. Circ Res 106:1384–1393

    Article  CAS  PubMed  Google Scholar 

Download references

Funding

None. Open access funding provided by Università degli Studi di Verona within the CRUI-CARE Agreement. No funding to be declared.

Author information

Authors and Affiliations

  1. Department of Nephrology, School of Medicine, Suleyman Demirel University, Isparta, Turkey

    Baris Afsar & Rengin Elsurer Afsar

Authors
  1. Baris Afsar
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rengin Elsurer Afsar
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

This manuscript was completely conceived and written by BA. REA: read the paper, suggested notes and revision, validated the final manuscript submitted.

Corresponding author

Correspondence to Baris Afsar.

Ethics declarations

Conflict of interest

The Authors state they have no conflict of interest.

Ethical approval

Not applicable.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Afsar, B., Afsar, R.E. Hypertension and cellular senescence. Biogerontology 24, 457–478 (2023). https://doi.org/10.1007/s10522-023-10031-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10522-023-10031-4

Keywords

Search

Navigation