REFERENCES

1. Kazi DS, Elkind MSV, Deutsch A, et al. Forecasting the economic burden of cardiovascular disease and stroke in the United States through 2050: a presidential advisory from the American heart association. Circulation. 2024;150:e89-101.

2. Martin SS, Aday AW, Almarzooq ZI, et al. 2024 heart disease and stroke statistics: a report of US and global data from the American heart association. Circulation. 2024;149:e347-913.

3. Forouzanfar MH, Alexander L, Anderson HR, et al. Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks in 188 countries, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015;386:2287-323.

4. Olshansky SJ, Goldman DP, Zheng Y, Rowe JW. Aging in America in the twenty-first century: demographic forecasts from the MacArthur Foundation Research Network on an Aging Society. Milbank Q. 2009;87:842-62.

5. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part I: aging arteries: a “set up” for vascular disease. Circulation. 2003;107:139-46.

6. Seals DR, Kaplon RE, Gioscia-Ryan RA, LaRocca TJ. You’re only as old as your arteries: translational strategies for preserving vascular endothelial function with aging. Physiology. 2014;29:250-64.

7. Abdellatif M, Rainer PP, Sedej S, Kroemer G. Hallmarks of cardiovascular ageing. Nat Rev Cardiol. 2023;20:754-77.

8. Ungvari Z, Tarantini S, Donato AJ, Galvan V, Csiszar A. Mechanisms of vascular aging. Circ Res. 2018;123:849-67.

9. Fleenor BS, Seals DR, Zigler ML, Sindler AL. Superoxide-lowering therapy with TEMPOL reverses arterial dysfunction with aging in mice. Aging Cell. 2012;11:269-76.

10. Lesniewski LA, Durrant JR, Connell ML, Folian BJ, Donato AJ, Seals DR. Salicylate treatment improves age-associated vascular endothelial dysfunction: potential role of nuclear factor κB and forkhead box O phosphorylation. J Gerontol A Biol Sci Med Sci. 2011;66:409-18.

11. Campisi J, d'Adda di Fagagna F. Cellular senescence: when bad things happen to good cells. Nat Rev Mol Cell Biol. 2007;8:729-40.

12. Yousefzadeh MJ, Zhao J, Bukata C, et al. Tissue specificity of senescent cell accumulation during physiologic and accelerated aging of mice. Aging Cell. 2020;19:e13094.

13. Clayton ZS, Rossman MJ, Mahoney SA, et al. Cellular senescence contributes to large elastic artery stiffening and endothelial dysfunction with aging: amelioration with senolytic treatment. Hypertension. 2023;80:2072-87.

14. Chen MS, Lee RT, Garbern JC. Senescence mechanisms and targets in the heart. Cardiovasc Res. 2022;118:1173-87.

15. Green DJ, Jones H, Thijssen D, Cable NT, Atkinson G. Flow-mediated dilation and cardiovascular event prediction: does nitric oxide matter?. Hypertension. 2011;57:363-9.

16. Mitchell GF, Hwang SJ, Vasan RS, et al. Arterial stiffness and cardiovascular events: the Framingham Heart Study. Circulation. 2010;121:505-11.

17. Chirinos JA, Segers P, Hughes T, Townsend R. Large-artery stiffness in health and disease: JACC state-of-the-art review. J Am Coll Cardiol. 2019;74:1237-63.

18. Owens GK, Kumar MS, Wamhoff BR. Molecular regulation of vascular smooth muscle cell differentiation in development and disease. Physiol Rev. 2004;84:767-801.

19. Townsend RR, Wilkinson IB, Schiffrin EL, et al. Recommendations for improving and standardizing vascular research on arterial stiffness: a scientific statement from the American Heart Association. Hypertension. 2015;66:698-722.

20. Seals DR, Jablonski KL, Donato AJ. Aging and vascular endothelial function in humans. Clin Sci. 2011;120:357-75.

21. Cahill PA, Redmond EM. Vascular endothelium - gatekeeper of vessel health. Atherosclerosis. 2016;248:97-109.

22. Harrison DG. Cellular and molecular mechanisms of endothelial cell dysfunction. J Clin Invest. 1997;100:2153-7.

23. Steven S, Frenis K, Oelze M, et al. Vascular inflammation and oxidative stress: major triggers for cardiovascular disease. Oxid Med Cell Longev. 2019;2019:7092151.

24. Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal. 2011;15:1583-606.

25. van der Loo B, Labugger R, Skepper JN, et al. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med. 2000;192:1731-44.

26. Hsieh HJ, Liu CA, Huang B, Tseng AHH, Wang DL. Shear-induced endothelial mechanotransduction: the interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J Biomed Sci. 2014;21:3.

27. Faleeva M, Ahmad S, Theofilatos K, et al. Sox9 accelerates vascular aging by regulating extracellular matrix composition and stiffness. Circ Res. 2024;134:307-24.

28. Bellien J, Favre J, Iacob M, et al. Arterial stiffness is regulated by nitric oxide and endothelium-derived hyperpolarizing factor during changes in blood flow in humans. Hypertension. 2010;55:674-80.

29. Campisi J. Aging, cellular senescence, and cancer. Annu Rev Physiol. 2013;75:685-705.

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

31. González-Gualda E, Baker AG, Fruk L, Muñoz-Espín D. A guide to assessing cellular senescence in vitro and in vivo. FEBS J. 2021;288:56-80.

32. Demaria M, Ohtani N, Youssef SA, et al. An essential role for senescent cells in optimal wound healing through secretion of PDGF-AA. Dev Cell. 2014;31:722-33.

33. Baker DJ, Wijshake T, Tchkonia T, et al. Clearance of p16INK4a-positive senescent cells delays ageing-associated disorders. Nature. 2011;479:232-6.

34. Han Y, Kim SY. Endothelial senescence in vascular diseases: current understanding and future opportunities in senotherapeutics. Exp Mol Med. 2023;55:1-12.

35. Hu C, Zhang X, Teng T, Ma ZG, Tang QZ. Cellular senescence in cardiovascular diseases: a systematic review. Aging Dis. 2022;13:103-28.

36. Childs BG, Baker DJ, Wijshake T, Conover CA, Campisi J, van Deursen JM. Senescent intimal foam cells are deleterious at all stages of atherosclerosis. Science. 2016;354:472-7.

37. Cho JH, Kim EC, Son Y, et al. CD9 induces cellular senescence and aggravates atherosclerotic plaque formation. Cell Death Differ. 2020;27:2681-96.

38. Born E, Lipskaia L, Breau M, et al. Eliminating senescent cells can promote pulmonary hypertension development and progression. Circulation. 2023;147:650-66.

39. Gao P, Gao P, Zhao J, et al. MKL1 cooperates with p38MAPK to promote vascular senescence, inflammation, and abdominal aortic aneurysm. Redox Biol. 2021;41:101903.

40. Bloom SI, Liu Y, Tucker JR, et al. Endothelial cell telomere dysfunction induces senescence and results in vascular and metabolic impairments. Aging Cell. 2023;22:e13875.

41. Jia G, Aroor AR, Jia C, Sowers JR. Endothelial cell senescence in aging-related vascular dysfunction. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1802-9.

42. Rossman MJ, Kaplon RE, Hill SD, et al. 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:H890-5.

43. Chi C, Li DJ, Jiang YJ, et al. Vascular smooth muscle cell senescence and age-related diseases: state of the art. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1810-21.

44. Katsuumi G, Shimizu I, Yoshida Y, Minamino T. Vascular senescence in cardiovascular and metabolic diseases. Front Cardiovasc Med. 2018;5:18.

45. Dimri GP, Lee X, Basile G, et al. A biomarker that identifies senescent human cells in culture and in aging skin in vivo. Proc Natl Acad Sci USA. 1995;92:9363-7.

46. Zhu Y, Tchkonia T, Pirtskhalava T, et al. The Achilles’ heel of senescent cells: from transcriptome to senolytic drugs. Aging Cell. 2015;14:644-58.

47. Rossman MJ, Gioscia-Ryan RA, Clayton ZS, Murphy MP, Seals DR. Targeting mitochondrial fitness as a strategy for healthy vascular aging. Clin Sci. 2020;134:1491-519.

48. Miwa S, Kashyap S, Chini E, von Zglinicki T. Mitochondrial dysfunction in cell senescence and aging. J Clin Invest. 2022;132:e158447.

49. Wiley CD, Velarde MC, Lecot P, et al. Mitochondrial dysfunction induces senescence with a distinct secretory phenotype. Cell Metab. 2016;23:303-14.

50. Victorelli S, Salmonowicz H, Chapman J, et al. Apoptotic stress causes mtDNA release during senescence and drives the SASP. Nature. 2023;622:627-36.

51. Mahoney SA, Dey AK, Basisty N, Herman AB. Identification and functional analysis of senescent cells in the cardiovascular system using omics approaches. Am J Physiol Heart Circ Physiol. 2023;325:H1039-58.

52. Erusalimsky JD. Vascular endothelial senescence: from mechanisms to pathophysiology. J Appl Physiol (1985). 2009;106:326-32.

53. Nguyen MT, Vryer R, Ranganathan S, et al. Telomere length and vascular phenotypes in a population-based cohort of children and midlife adults. J Am Heart Assoc. 2019;8:e012707.

54. Chiu JJ, Chien S. Effects of disturbed flow on vascular endothelium: pathophysiological basis and clinical perspectives. Physiol Rev. 2011;91:327-87.

55. Okuda K, Khan MY, Skurnick J, Kimura M, Aviv H, Aviv A. Telomere attrition of the human abdominal aorta: relationships with age and atherosclerosis. Atherosclerosis. 2000;152:391-8.

56. Kotla S, Vu HT, Ko KA, et al. Endothelial senescence is induced by phosphorylation and nuclear export of telomeric repeat binding factor 2-interacting protein. JCI Insight. 2019;4:124867.

57. Warboys CM, de Luca A, Amini N, et al. Disturbed flow promotes endothelial senescence via a p53-dependent pathway. Arterioscler Thromb Vasc Biol. 2014;34:985-95.

58. VanderLaan PA, Reardon CA, Getz GS. Site specificity of atherosclerosis: site-selective responses to atherosclerotic modulators. Arterioscler Thromb Vasc Biol. 2004;24:12-22.

59. Li Y, Liu Z, Han X, et al. Dynamics of endothelial cell generation and turnover in arteries during homeostasis and diseases. Circulation. 2024;149:135-54.

60. Jones RC, Karkanias J, Krasnow MA, et al. The tabula sapiens: a multiple-organ, single-cell transcriptomic atlas of humans. Science. 2022;376:eabl4896.

61. Jacobsen K, Lund MB, Shim J, et al. Diverse cellular architecture of atherosclerotic plaque derives from clonal expansion of a few medial SMCs. JCI Insight. 2017;2:95890.

62. Misra A, Feng Z, Chandran RR, et al. Integrin beta3 regulates clonality and fate of smooth muscle-derived atherosclerotic plaque cells. Nat Commun. 2018;9:2073.

63. Chappell J, Harman JL, Narasimhan VM, et al. Extensive proliferation of a subset of differentiated, yet plastic, medial vascular smooth muscle cells contributes to neointimal formation in mouse injury and atherosclerosis models. Circ Res. 2016;119:1313-23.

64. McDonald AI, Shirali AS, Aragón R, et al. Endothelial regeneration of large vessels is a biphasic process driven by local cells with distinct proliferative capacities. Cell Stem Cell. 2018;23:210-25.e6.

65. Mahoney SA, Venkatasubramanian R, Darrah MA, et al. Intermittent supplementation with fisetin improves arterial function in old mice by decreasing cellular senescence. Aging Cell. 2024;23:e14060.

66. Conboy MJ, Conboy IM, Rando TA. Heterochronic parabiosis: historical perspective and methodological considerations for studies of aging and longevity. Aging Cell. 2013;12:525-30.

67. Jeon OH, Mehdipour M, Gil TH, et al. Systemic induction of senescence in young mice after single heterochronic blood exchange. Nat Metab. 2022;4:995-1006.

68. Craighead DH, Heinbockel TC, Freeberg KA, et al. Time-efficient inspiratory muscle strength training lowers blood pressure and improves endothelial function, NO bioavailability, and oxidative stress in midlife/older adults with above-normal blood pressure. J Am Heart Assoc. 2021;10:e020980.

69. Rossman MJ, Gioscia-Ryan RA, Santos-Parker JR, et al. Inorganic nitrite supplementation improves endothelial function with aging: translational evidence for suppression of mitochondria-derived oxidative stress. Hypertension. 2021;77:1212-22.

70. Mahoney SA, VanDongen NS, Greenberg NT, et al. Role of the circulating milieu in age-related arterial dysfunction: a novel ex vivo approach. Am J Physiol Heart Circ Physiol. 2024;326:H1279-90.

71. Kiss T, Tarantini S, Csipo T, et al. Circulating anti-geronic factors from heterochonic parabionts promote vascular rejuvenation in aged mice: transcriptional footprint of mitochondrial protection, attenuation of oxidative stress, and rescue of endothelial function by young blood. Geroscience. 2020;42:727-48.

72. Bloom SI, Islam MT, Lesniewski LA, Donato AJ. Mechanisms and consequences of endothelial cell senescence. Nat Rev Cardiol. 2023;20:38-51.

73. Lee AH, Ghosh D, Koh IL, Dawson MR. Senescence-associated exosomes transfer miRNA-induced fibrosis to neighboring cells. Aging. 2023;15:1237-56.

74. Terlecki-Zaniewicz L, Lämmermann I, Latreille J, et al. Small extracellular vesicles and their miRNA cargo are anti-apoptotic members of the senescence-associated secretory phenotype. Aging. 2018;10:1103-32.

75. Amersfoort J, Eelen G, Carmeliet P. Immunomodulation by endothelial cells - partnering up with the immune system?. Nat Rev Immunol. 2022;22:576-88.

76. Uryga AK, Grootaert MOJ, Garrido AM, et al. Telomere damage promotes vascular smooth muscle cell senescence and immune cell recruitment after vessel injury. Commun Biol. 2021;4:611.

77. Mazan-Mamczarz K, Tsitsipatis D, Carr A, et al. Single-cell and spatial transcriptomics uncovers the role of senescent vascular cells in pathological arterial remodeling during atherosclerosis. Research Square Platform LLC; 2023.

78. Krouwer VJ, Hekking LH, Langelaar-Makkinje M, Regan-Klapisz E, Post JA. Endothelial cell senescence is associated with disrupted cell-cell junctions and increased monolayer permeability. Vasc Cell. 2012;4:12.

79. Mun GI, Boo YC. Identification of CD44 as a senescence-induced cell adhesion gene responsible for the enhanced monocyte recruitment to senescent endothelial cells. Am J Physiol Heart Circ Physiol. 2010;298:H2102-11.

80. Real MGC, Falcione SR, Boghozian R, et al. Endothelial cell senescence effect on the blood-brain barrier in stroke and cognitive impairment. Neurology. 2024;103:e210063.

81. Beidokhti M, Villalba N, Ma Y, Reynolds A, Villamil JH, Yuan SY. Lung endothelial cell senescence impairs barrier function and promotes neutrophil adhesion and migration. Geroscience. 2025. Online ahead of print.

82. Tang L, Zhang C, Yang Q, et al. Melatonin maintains inner blood-retinal barrier via inhibition of p38/TXNIP/NF-κB pathway in diabetic retinopathy. J Cell Physiol. 2021;236:5848-64.

83. Parrinello S, Samper E, Krtolica A, Goldstein J, Melov S, Campisi J. Oxygen sensitivity severely limits the replicative lifespan of murine fibroblasts. Nat Cell Biol. 2003;5:741-7.

84. Busuttil RA, Rubio M, Dollé ME, Campisi J, Vijg J. Oxygen accelerates the accumulation of mutations during the senescence and immortalization of murine cells in culture. Aging Cell. 2003;2:287-94.

85. Roos CM, Zhang B, Palmer AK, et al. Chronic senolytic treatment alleviates established vasomotor dysfunction in aged or atherosclerotic mice. Aging Cell. 2016;15:973-7.

86. Ko CH, Takahashi JS. Molecular components of the mammalian circadian clock. Hum Mol Genet. 2006;15:R271-7.

87. Bunger MK, Wilsbacher LD, Moran SM, et al. Mop3 is an essential component of the master circadian pacemaker in mammals. Cell. 2000;103:1009-17.

88. Rey G, Cesbron F, Rougemont J, Reinke H, Brunner M, Naef F. Genome-wide and phase-specific DNA-binding rhythms of BMAL1 control circadian output functions in mouse liver. PLoS Biol. 2011;9:e1000595.

89. Menet JS, Pescatore S, Rosbash M. CLOCK:BMAL1 is a pioneer-like transcription factor. Genes Dev. 2014;28:8-13.

90. Crnko S, Cour M, Van Laake LW, Lecour S. Vasculature on the clock: Circadian rhythm and vascular dysfunction. Vascul Pharmacol. 2018;108:1-7.

91. Fan R, Peng X, Xie L, et al. Importance of bmal1 in Alzheimer's disease and associated aging-related diseases: mechanisms and interventions. Aging Cell. 2022;21:e13704.

92. Bhatwadekar AD, Beli E, Diao Y, et al. Conditional deletion of bmal1 accentuates microvascular and macrovascular injury. Am J Pathol. 2017;187:1426-35.

93. Jachim SK, Zhong J, Ordog T, et al. BMAL1 modulates senescence programming via AP-1. Aging. 2023;15:9984-10009.

94. Rafikov R, Sun X, Rafikova O, et al. Complex I dysfunction underlies the glycolytic switch in pulmonary hypertensive smooth muscle cells. Redox Biol. 2015;6:278-86.

95. Wiley CD, Campisi J. From ancient pathways to aging cells-connecting metabolism and cellular senescence. Cell Metab. 2016;23:1013-21.

96. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. Hallmarks of aging: an expanding universe. Cell. 2023;186:243-78.

97. der Bruggen MM, Spronck B, Delhaas T, Reesink KD, Schalkwijk CG. The putative role of methylglyoxal in arterial stiffening: a review. Heart Lung Circ. 2021;30:1681-93.

98. Aragonès G, Rowan S, Francisco SG, et al. The glyoxalase system in age-related diseases: nutritional intervention as anti-ageing strategy. Cells. 2021;10:1852.

99. Halkoum R, Salnot V, Capallere C, et al. Glyoxal induces senescence in human keratinocytes through oxidative stress and activation of the protein kinase B/FOXO3a/p27KIP1 pathway. J Invest Dermatol. 2022;142:2068-78.e7.

100. Li H, Zheng L, Chen C, Liu X, Zhang W. Brain senescence caused by elevated levels of reactive metabolite methylglyoxal on D-galactose-induced aging mice. Front Neurosci. 2019;13:1004.

101. Ikeda Y, Inagi R, Miyata T, et al. Glyoxalase I retards renal senescence. Am J Pathol. 2011;179:2810-21.

102. Jo-Watanabe A, Ohse T, Nishimatsu H, et al. Glyoxalase I reduces glycative and oxidative stress and prevents age-related endothelial dysfunction through modulation of endothelial nitric oxide synthase phosphorylation. Aging Cell. 2014;13:519-28.

103. Ziegler DV, Martin N, Bernard D. Cellular senescence links mitochondria-ER contacts and aging. Commun Biol. 2021;4:1323.

104. Wang J, Bai Y, Zhao X, et al. oxLDL-mediated cellular senescence is associated with increased NADPH oxidase p47phox recruitment to caveolae. Biosci Rep. 2018;38:BSR20180283.

105. Yu S, Zhang L, Liu C, Yang J, Zhang J, Huang L. PACS2 is required for ox-LDL-induced endothelial cell apoptosis by regulating mitochondria-associated ER membrane formation and mitochondrial Ca2+ elevation. Exp Cell Res. 2019;379:191-202.

106. Ziegler DV, Vindrieux D, Goehrig D, et al. Calcium channel ITPR2 and mitochondria-ER contacts promote cellular senescence and aging. Nat Commun. 2021;12:720.

107. Bolinches-Amorós A, Mollá B, Pla-Martín D, Palau F, González-Cabo P. Mitochondrial dysfunction induced by frataxin deficiency is associated with cellular senescence and abnormal calcium metabolism. Front Cell Neurosci. 2014;8:124.

108. Rodríguez LR, Calap-Quintana P, Lapeña-Luzón T, et al. Oxidative stress modulates rearrangement of endoplasmic reticulum-mitochondria contacts and calcium dysregulation in a Friedreich's ataxia model. Redox Biol. 2020;37:101762.

109. Piera-Velazquez S, Jimenez SA. Endothelial to mesenchymal transition: role in physiology and in the pathogenesis of human diseases. Physiol Rev. 2019;99:1281-324.

110. Ramadhiani R, Ikeda K, Hirata KI, Emoto N. Endothelial cell senescence exacerbates pulmonary fibrosis potentially through accelerated endothelial to mesenchymal transition. Kobe J Med Sci. 2021;67:E84-91.

111. Zhu J, Angelov S, Alp Yildirim I, et al. Loss of transforming growth factor beta signaling in aortic smooth muscle cells causes endothelial dysfunction and aortic hypercontractility. Arterioscler Thromb Vasc Biol. 2021;41:1956-71.

112. Fleenor BS, Marshall KD, Durrant JR, Lesniewski LA, Seals DR. Arterial stiffening with ageing is associated with transforming growth factor-β1-related changes in adventitial collagen: reversal by aerobic exercise. J Physiol. 2010;588:3971-82.

113. Fleenor BS, Marshall KD, Rippe C, Seals DR. Replicative aging induces endothelial to mesenchymal transition in human aortic endothelial cells: potential role of inflammation. J Vasc Res. 2012;49:59-64.

114. Hamczyk MR, Nevado RM, Barettino A, Fuster V, Andrés V. Biological versus chronological aging: JACC focus seminar. J Am Coll Cardiol. 2020;75:919-30.

115. Sharma R, Oni OA, Gupta K, et al. Normalization of testosterone level is associated with reduced incidence of myocardial infarction and mortality in men. Eur Heart J. 2015;36:2706-15.

116. Vlachopoulos C, Ioakeimidis N, Miner M, et al. Testosterone deficiency: a determinant of aortic stiffness in men. Atherosclerosis. 2014;233:278-83.

117. Yildiz O, Seyrek M. Vasodilating mechanisms of testosterone. Exp Clin Endocrinol Diabetes. 2007;115:1-6.

118. Novella S, Dantas AP, Segarra G, et al. Gathering of aging and estrogen withdrawal in vascular dysfunction of senescent accelerated mice. Exp Gerontol. 2010;45:868-74.

119. Maeda M, Hayashi T, Mizuno N, Hattori Y, Kuzuya M. Intermittent high glucose implements stress-induced senescence in human vascular endothelial cells: role of superoxide production by NADPH oxidase. PLoS One. 2015;10:e0123169.

120. Farhat N, Thorin-Trescases N, Voghel G, et al. Stress-induced senescence predominates in endothelial cells isolated from atherosclerotic chronic smokers. Can J Physiol Pharmacol. 2008;86:761-9.

121. Carreras A, Zhang SX, Peris E, et al. Chronic sleep fragmentation induces endothelial dysfunction and structural vascular changes in mice. Sleep. 2014;37:1817-24.

122. Satyjeet F, Naz S, Kumar V, et al. Psychological stress as a risk factor for cardiovascular disease: a case-control study. Cureus. 2020;12:e10757.

123. Vancheri F, Longo G, Vancheri E, Henein MY. Mental stress and cardiovascular health-part I. J Clin Med. 2022;11:3353.

124. Sara JDS, Toya T, Ahmad A, et al. Mental stress and its effects on vascular health. Mayo Clin Proc. 2022;97:951-90.

125. Sara JDS, Lerman LO, Lerman A. What can biologic aging tell us about the effects of mental stress on vascular health. Hypertension. 2023;80:2515-22.

126. Hayashi T, Yano K, Matsui-Hirai H, Yokoo H, Hattori Y, Iguchi A. Nitric oxide and endothelial cellular senescence. Pharmacol Ther. 2008;120:333-9.

127. Lin YF, Wang LY, Chen CS, Li CC, Hsiao YH. Cellular senescence as a driver of cognitive decline triggered by chronic unpredictable stress. Neurobiol Stress. 2021;15:100341.

128. Rentscher KE, Carroll JE, Repetti RL, Cole SW, Reynolds BM, Robles TF. Chronic stress exposure and daily stress appraisals relate to biological aging marker p16INK4a. Psychoneuroendocrinology. 2019;102:139-48.

129. Jimenez DE, Alegría M, Chen CN, Chan D, Laderman M. Prevalence of psychiatric illnesses in older ethnic minority adults. J Am Geriatr Soc. 2010;58:256-64.

130. Pietrzak RH, Goldstein RB, Southwick SM, Grant BF. Prevalence and axis I comorbidity of full and partial posttraumatic stress disorder in the United States: results from wave 2 of the national epidemiologic survey on alcohol and related conditions. J Anxiety Disord. 2011;25:456-65.

131. Kaiser A, Cook JM, Glick DM, Moye J. Posttraumatic stress disorder in older adults: a conceptual review. Clin Gerontol. 2019;42:359-76.

132. Wolf EJ, Morrison FG. Traumatic stress and accelerated cellular aging: from epigenetics to cardiometabolic disease. Curr Psychiatry Rep. 2017;19:75.

133. Lohr JB, Palmer BW, Eidt CA, et al. Is post-traumatic stress disorder associated with premature senescence? A review of the literature. Am J Geriatr Psychiatry. 2015;23:709-25.

134. Wang Y, Boerma M, Zhou D. Ionizing radiation-induced endothelial cell senescence and cardiovascular diseases. Radiat Res. 2016;186:153-61.

135. Zheng X, Liu Z, Bin Y, et al. Ionizing radiation induces vascular smooth muscle cell senescence through activating NF-κB/CTCF/p16 pathway. Biochim Biophys Acta Mol Basis Dis. 2024;1870:166994.

136. Yamamoto Y, Minami M, Yoshida K, et al. Irradiation accelerates plaque formation and cellular senescence in flow-altered carotid arteries of apolipoprotein E knock-out mice. J Am Heart Assoc. 2021;10:e020712.

137. Fernández-Alvarez V, Nieto CS, Alvarez FL. Arterial stiffness as an ultrasound biomarker of radiation-induced carotid artery disease. Vasa. 2021;50:348-55.

138. Bansal N, Amdani SM, Hutchins KK, Lipshultz SE. Cardiovascular disease in survivors of childhood cancer. Curr Opin Pediatr. 2018;30:628-38.

139. Lipshultz SE, Karnik R, Sambatakos P, Franco VI, Ross SW, Miller TL. Anthracycline-related cardiotoxicity in childhood cancer survivors. Curr Opin Cardiol. 2014;29:103-12.

140. Cappetta D, Rossi F, Piegari E, et al. Doxorubicin targets multiple players: a new view of an old problem. Pharmacol Res. 2018;127:4-14.

141. Bourlon MT, Velazquez HE, Hinojosa J, et al. Immunosenescence profile and expression of the aging biomarker (p16INK4a) in testicular cancer survivors treated with chemotherapy. BMC Cancer. 2020;20:882.

142. Smitherman AB, Wood WA, Mitin N, et al. Accelerated aging among childhood, adolescent, and young adult cancer survivors is evidenced by increased expression of p16INK4a and frailty. Cancer. 2020;126:4975-83.

143. Muss HB, Smitherman A, Wood WA, et al. p16 a biomarker of aging and tolerance for cancer therapy. Transl Cancer Res. 2020;9:5732-42.

144. Clayton ZS, Hutton DA, Mahoney SA, Seals DR. Anthracycline chemotherapy-mediated vascular dysfunction as a model of accelerated vascular aging. Aging Cancer. 2021;2:45-69.

145. Hutton D, Brunt V, Mahoney S, et al. Cellular senescence mediates doxorubicin-induced arterial dysfunction via activation of mitochondrial oxidative stress and the mammalian target of rapamycin. FASEB J. 2021;35:00283.

146. Jain D, Ahmad T, Cairo M, Aronow W. Cardiotoxicity of cancer chemotherapy: identification, prevention and treatment. Ann Transl Med. 2017;5:348.

147. Axel DI, Kunert W, Göggelmann C, et al. Paclitaxel inhibits arterial smooth muscle cell proliferation and migration in vitro and in vivo using local drug delivery. Circulation. 1997;96:636-45.

148. Ahire C, Nyul-Toth A, DelFavero J, et al. Accelerated cerebromicrovascular senescence contributes to cognitive decline in a mouse model of paclitaxel (Taxol)-induced chemobrain. Aging Cell. 2023;22:e13832.

149. Kanmogne GD. HIV Infection, antiretroviral drugs, and the vascular endothelium. Cells. 2024;13:672.

150. Gianesin K, Noguera-Julian A, Zanchetta M, et al. Premature aging and immune senescence in HIV-infected children. AIDS. 2016;30:1363-73.

151. Kuehnemann C, Hughes JB, Desprez PY, Melov S, Wiley CD, Campisi J. Antiretroviral protease inhibitors induce features of cellular senescence that are reversible upon drug removal. Aging Cell. 2023;22:e13750.

152. Cohen J, D'Agostino L, Tuzer F, Torres C. HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs. Mech Ageing Dev. 2018;175:74-82.

153. Kaur G, Sohanur Rahman M, Shaikh S, et al. Emerging roles of senolytics/senomorphics in HIV-related co-morbidities. Biochem Pharmacol. 2024;228:116179.

154. Matthews C, Gorenne I, Scott S, et al. Vascular smooth muscle cells undergo telomere-based senescence in human atherosclerosis: effects of telomerase and oxidative stress. Circ Res. 2006;99:156-64.

155. Wang J, Uryga AK, Reinhold J, et al. Vascular smooth muscle cell senescence promotes atherosclerosis and features of plaque vulnerability. Circulation. 2015;132:1909-19.

156. van der Feen DE, Bossers GPL, Hagdorn QAJ, et al. Cellular senescence impairs the reversibility of pulmonary arterial hypertension. Sci Transl Med. 2020;12:eaaw4974.

157. Chen HZ, Wang F, Gao P, et al. Age-associated sirtuin 1 reduction in vascular smooth muscle links vascular senescence and inflammation to abdominal aortic aneurysm. Circ Res. 2016;119:1076-88.

158. Tyrrell DJ, Chen J, Li BY, et al. Aging alters the aortic proteome in health and thoracic aortic aneurysm. Arterioscler Thromb Vasc Biol. 2022;42:1060-76.

159. Minamino T, Komuro I. Vascular cell senescence: contribution to atherosclerosis. Circ Res. 2007;100:15-26.

160. Sun Y, Wang X, Liu T, Zhu X, Pan X. The multifaceted role of the SASP in atherosclerosis: from mechanisms to therapeutic opportunities. Cell Biosci. 2022;12:74.

161. Lu H, Du W, Ren L, et al. Vascular smooth muscle cells in aortic aneurysm: from genetics to mechanisms. J Am Heart Assoc. 2021;10:e023601.

162. Noureddine H, Gary-Bobo G, Alifano M, et al. Pulmonary artery smooth muscle cell senescence is a pathogenic mechanism for pulmonary hypertension in chronic lung disease. Circ Res. 2011;109:543-53.

163. Gonzalo S, Kreienkamp R, Askjaer P. Hutchinson-gilford progeria syndrome: a premature aging disease caused by LMNA gene mutations. Ageing Res Rev. 2017;33:18-29.

164. Xu Q, Mojiri A, Boulahouache L, Morales E, Walther BK, Cooke JP. Vascular senescence in progeria: role of endothelial dysfunction. Eur Heart J Open. 2022;2:oeac047.

165. Wong A, Kieu T, Robbins PD. The Ercc1-/Δ mouse model of accelerated senescence and aging for identification and testing of novel senotherapeutic interventions. Aging. 2020;12:24481-3.

166. Ataei Ataabadi E, Golshiri K, van der Linden J, et al. Vascular ageing features caused by selective DNA damage in smooth muscle cell. Oxid Med Cell Longev. 2021;2021:2308317.

167. Shamanna RA, Croteau DL, Lee JH, Bohr VA. Recent advances in understanding werner syndrome. F1000Res. 2017;6:1779.

168. Kato H, Maezawa Y. Atherosclerosis and cardiovascular diseases in progeroid syndromes. J Atheroscler Thromb. 2022;29:439-47.

169. Norwood TH, Hoehn H, Salk D, Martin GM. Cellular aging in Werner's syndrome: a unique phenotype?. J Invest Dermatol. 1979;73:92-6.

170. Paul SK, Oshima M, Patil A, et al. Retrotransposons in Werner syndrome-derived macrophages trigger type I interferon-dependent inflammation in an atherosclerosis model. Nat Commun. 2024;15:4772.

171. Zhu JL, Hasle H, Correa A, et al. Survival among people with down syndrome: a nationwide population-based study in denmark. Genet Med. 2013;15:64-9.

172. Cappelli-Bigazzi M, Santoro G, Battaglia C, et al. Endothelial cell function in patients with down's syndrome. Am J Cardiol. 2004;94:392-5.

173. Koike MA, Green KN, Blurton-Jones M, Laferla FM. Oligemic hypoperfusion differentially affects tau and amyloid-β. Am J Pathol. 2010;177:300-10.

174. Garcia-Alloza M, Gregory J, Kuchibhotla KV, et al. Cerebrovascular lesions induce transient β-amyloid deposition. Brain. 2011;134:3697-707.

175. Wee SO, Rosenberg AJ, Kanokwan B, Griffith G, Baynard T, Fernhall B. Carotid vascular blood flow in individuals with down syndrome following low body negative pressure challenge. FASEB J. 2017;31:840.21.

176. Meharena HS, Marco A, Dileep V, et al. Down-syndrome-induced senescence disrupts the nuclear architecture of neural progenitors. Cell Stem Cell. 2022;29:116-30.e7.

177. Gimeno A, García-Giménez JL, Audí L, et al. Decreased cell proliferation and higher oxidative stress in fibroblasts from Down Syndrome fetuses. Preliminary study. Biochim Biophys Acta. 2014;1842:116-25.

178. de Arruda Cardoso Smith M, Borsatto-Galera B, Feller RI, et al. Telomeres on chromosome 21 and aging in lymphocytes and gingival fibroblasts from individuals with Down syndrome. J Oral Sci. 2004;46:171-7.

179. Zhang L, Pitcher LE, Prahalad V, Niedernhofer LJ, Robbins PD. Targeting cellular senescence with senotherapeutics: senolytics and senomorphics. FEBS J. 2023;290:1362-83.

180. Chen XK, Yi ZN, Wong GTC, et al. Is exercise a senolytic medicine? A systematic review. Aging Cell. 2021;20:e13294.

181. Lynch DH, Petersen CL, Stewart D, et al. Changes in senescence markers after a weight loss intervention in older adults with obesity. Arch Gerontol Geriatr. 2025;129:105685.

182. Wang B, Han J, Elisseeff JH, Demaria M. The senescence-associated secretory phenotype and its physiological and pathological implications. Nat Rev Mol Cell Biol. 2024;25:958-78.

183. Kirkland JL, Tchkonia T. Senolytic drugs: from discovery to translation. J Intern Med. 2020;288:518-36.

184. Zhu Y, Tchkonia T, Fuhrmann-Stroissnigg H, et al. Identification of a novel senolytic agent, navitoclax, targeting the Bcl-2 family of anti-apoptotic factors. Aging Cell. 2016;15:428-35.

185. Wilson WH, O'Connor OA, Czuczman MS, et al. Navitoclax, a targeted high-affinity inhibitor of BCL-2, in lymphoid malignancies: a phase 1 dose-escalation study of safety, pharmacokinetics, pharmacodynamics, and antitumour activity. Lancet Oncol. 2010;11:1149-59.

186. Karnewar S, Karnewar V, Shankman LS, Owens GK. Treatment of advanced atherosclerotic mice with ABT-263 reduced indices of plaque stability and increased mortality. JCI Insight. 2024;9:e173863.

187. Garrido AM, Kaistha A, Uryga AK, et al. Efficacy and limitations of senolysis in atherosclerosis. Cardiovasc Res. 2022;118:1713-27.

188. Childs BG, Zhang C, Shuja F, et al. Senescent cells suppress innate smooth muscle cell repair functions in atherosclerosis. Nat Aging. 2021;1:698-714.

189. Justice JN, Nambiar AM, Tchkonia T, et al. Senolytics in idiopathic pulmonary fibrosis: results from a first-in-human, open-label, pilot study. EBioMedicine. 2019;40:554-63.

190. Gonzales MM, Garbarino VR, Kautz T, et al. Senolytic therapy to modulate the progression of Alzheimer's disease (SToMP-AD) - outcomes from the first clinical trial of senolytic therapy for Alzheimer's disease. Res Sq. 2023;rs.3.rs-2809973.

191. Parvizi M, Franchi F, Arendt BK, Ebtehaj S, Rodriguez-Porcel M, Lanza IR. Senolytic agents lessen the severity of abdominal aortic aneurysm in aged mice. Exp Gerontol. 2021;151:111416.

192. Yousefzadeh MJ, Zhu Y, McGowan SJ, et al. Fisetin is a senotherapeutic that extends health and lifespan. EBioMedicine. 2018;36:18-28.

193. Mahoney S, Ciotlos S, Darrah M, et al. 25-Hydroxycholesterol reduces aortic cellular senescence and stiffness in old mice. Physiology. 2023;38:5711505.

194. Johmura Y, Yamanaka T, Omori S, et al. Senolysis by glutaminolysis inhibition ameliorates various age-associated disorders. Science. 2021;371:265-70.

195. Suda M, Shimizu I, Katsuumi G, et al. Senolytic vaccination improves normal and pathological age-related phenotypes and increases lifespan in progeroid mice. Nat Aging. 2021;1:1117-26.

196. Ota H, Eto M, Kano MR, et al. Induction of endothelial nitric oxide synthase, SIRT1, and catalase by statins inhibits endothelial senescence through the Akt pathway. Arterioscler Thromb Vasc Biol. 2010;30:2205-11.

197. Abdelgawad IY, Agostinucci K, Sadaf B, Grant MKO, Zordoky BN. Metformin mitigates SASP secretion and LPS-triggered hyper-inflammation in Doxorubicin-induced senescent endothelial cells. Front Aging. 2023;4:1170434.

198. Oeseburg H, de Boer RA, Buikema H, van der Harst P, van Gilst WH, Silljé HH. Glucagon-like peptide 1 prevents reactive oxygen species-induced endothelial cell senescence through the activation of protein kinase A. Arterioscler Thromb Vasc Biol. 2010;30:1407-14.

199. Zhao L, Li AQ, Zhou TF, Zhang MQ, Qin XM. Exendin-4 alleviates angiotensin II-induced senescence in vascular smooth muscle cells by inhibiting Rac1 activation via a cAMP/PKA-dependent pathway. Am J Physiol Cell Physiol. 2014;307:C1130-41.

200. Bode-Böger SM, Martens-Lobenhoffer J, Täger M, Schröder H, Scalera F. Aspirin reduces endothelial cell senescence. Biochem Biophys Res Commun. 2005;334:1226-32.

201. Xia L, Wang XX, Hu XS, et al. Resveratrol reduces endothelial progenitor cells senescence through augmentation of telomerase activity by Akt-dependent mechanisms. Br J Pharmacol. 2008;155:387-94.

202. Csiszar A, Sosnowska D, Wang M, Lakatta EG, Sonntag WE, Ungvari Z. Age-associated proinflammatory secretory phenotype in vascular smooth muscle cells from the non-human primate Macaca mulatta: reversal by resveratrol treatment. J Gerontol A Biol Sci Med Sci. 2012;67:811-20.

203. Lesniewski LA, Seals DR, Walker AE, et al. Dietary rapamycin supplementation reverses age-related vascular dysfunction and oxidative stress, while modulating nutrient-sensing, cell cycle, and senescence pathways. Aging Cell. 2017;16:17-26.

204. Sasaki N, Itakura Y, Toyoda M. Rapamycin promotes endothelial-mesenchymal transition during stress-induced premature senescence through the activation of autophagy. Cell Commun Signal. 2020;18:43.

205. Schoenwaelder SM, Jarman KE, Gardiner EE, et al. Bcl-xL-inhibitory BH3 mimetics can induce a transient thrombocytopathy that undermines the hemostatic function of platelets. Blood. 2011;118:1663-74.

206. Breccia M, Molica M, Alimena G. How tyrosine kinase inhibitors impair metabolism and endocrine system function: a systematic updated review. Leuk Res. 2014;38:1392-8.

207. Crespo-Garcia S, Tsuruda PR, Dejda A, et al. Pathological angiogenesis in retinopathy engages cellular senescence and is amenable to therapeutic elimination via BCL-xL inhibition. Cell Metab. 2021;33:818-32.e7.

208. Crespo-Garcia S, Fournier F, Diaz-Marin R, et al. Therapeutic targeting of cellular senescence in diabetic macular edema: preclinical and phase 1 trial results. Nat Med. 2024;30:443-54.

209. Moiseeva V, Cisneros A, Sica V, et al. Senescence atlas reveals an aged-like inflamed niche that blunts muscle regeneration. Nature. 2023;613:169-78.

210. Wang B, Wang L, Gasek NS, et al. An inducible p21-Cre mouse model to monitor and manipulate p21-highly-expressing senescent cells in vivo. Nat Aging. 2021;1:962-73.

211. Li M, Wang D, Liu Z, et al. Assessing the effects of aging on the renal endothelial cell landscape using single-cell RNA sequencing. Front Genet. 2023;14:1175716.

212. Cohen C, Le Goff O, Soysouvanh F, et al. Glomerular endothelial cell senescence drives age-related kidney disease through PAI-1. EMBO Mol Med. 2021;13:e14146.

213. Amor C, Fernández-Maestre I, Chowdhury S, et al. Prophylactic and long-lasting efficacy of senolytic CAR T cells against age-related metabolic dysfunction. Nat Aging. 2024;4:336-49.

214. Grosse L, Wagner N, Emelyanov A, et al. Defined p16High senescent cell types are indispensable for mouse healthspan. Cell Metab. 2020;32:87-99.e6.

215. Omori S, Wang TW, Johmura Y, et al. Generation of a p16 reporter mouse and its use to characterize and target p16High cells in vivo. Cell Metab. 2020;32:814-28.e6.

216. Ozawa M, Mori H, Endo T, et al. Age-related decline in spermatogenic activity accompanied with endothelial cell senescence in male mice. iScience. 2023;26:108456.

217. Kiss T, Nyúl-Tóth Á, Balasubramanian P, et al. Single-cell RNA sequencing identifies senescent cerebromicrovascular endothelial cells in the aged mouse brain. Geroscience. 2020;42:429-44.

218. Ximerakis M, Lipnick SL, Innes BT, et al. Single-cell transcriptomic profiling of the aging mouse brain. Nat Neurosci. 2019;22:1696-708.

219. Hussong SA, Banh AQ, Van Skike CE, et al. Soluble pathogenic tau enters brain vascular endothelial cells and drives cellular senescence and brain microvascular dysfunction in a mouse model of tauopathy. Nat Commun. 2023;14:2367.

220. Gulej R, Nyúl-Tóth Á, Ahire C, et al. Elimination of senescent cells by treatment with Navitoclax/ABT263 reverses whole brain irradiation-induced blood-brain barrier disruption in the mouse brain. Geroscience. 2023;45:2983-3002.

221. Wang L, Wang B, Gasek NS, et al. Targeting p21Cip1 highly expressing cells in adipose tissue alleviates insulin resistance in obesity. Cell Metab. 2022;34:75-89.e8.

222. Lipskaia L, Breau M, Cayrou C, et al. mTert induction in p21-positive cells counteracts capillary rarefaction and pulmonary emphysema. EMBO Rep. 2024;25:1650-84.

223. Culley MK, Zhao J, Tai YY, et al. Frataxin deficiency promotes endothelial senescence in pulmonary hypertension. J Clin Invest. 2021;131:136459.

224. Gao Z, Santos RB, Rupert J, et al. Endothelial-specific telomerase inactivation causes telomere-independent cell senescence and multi-organ dysfunction characteristic of aging. Aging Cell. 2024;23:e14138.

225. Barinda AJ, Ikeda K, Nugroho DB, et al. Endothelial progeria induces adipose tissue senescence and impairs insulin sensitivity through senescence associated secretory phenotype. Nat Commun. 2020;11:481.

226. Islam MT, Hall SA, Dutson T, et al. Endothelial cell-specific reduction in mTOR ameliorates age-related arterial and metabolic dysfunction. Aging Cell. 2024;23:e14040.

The Journal of Cardiovascular Aging
ISSN 2768-5993 (Online)

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/

Portico

All published articles are preserved here permanently:

https://www.portico.org/publishers/oae/