Cellular Senescence Contributes to Large Elastic Artery Stiffening and Endothelial Dysfunction With Aging: Amelioration With Senolytic Treatment
Open accessAbstract
BACKGROUND: Here, we assessed the role of cellular senescence and the senescence associated secretory phenotype (SASP) in age-related aortic stiffening and endothelial dysfunction. METHODS: We studied young (6-8 mo) and old (27-29 mo) p16-3MR mice, which allows for genetic-based clearance of senescent cells with ganciclovir (GCV). We also treated old C57BL/6N mice with the senolytic ABT-263. RESULTS: In old mice, GCV reduced aortic stiffness assessed by aortic pulse wave velocity (PWV; 477±10 vs. 382±7 cm/s, P <0.05) to young levels (old-GCV vs. young-vehicle, P =0.35); ABT-263 also reduced aortic PWV in old mice (446±9 to 356±11 cm/s, P <0.05). Aortic adventitial collagen was reduced by GCV ( P <0.05) and ABT-263 ( P =0.12) in old mice. To show an effect of the circulating SASP, we demonstrated that plasma exposure from Old-vehicle p16-3MR mice, but not from Old-GCV mice, induced aortic stiffening assessed ex vivo (elastic modulus; P <0.05). Plasma proteomics implicated glycolysis in circulating SASP-mediated aortic stiffening. In old p16-3MR mice, GCV increased endothelial function assessed via peak carotid artery endothelium-dependent dilation (EDD; Old-GCV, 94±1% vs. Old-vehicle, 84±2%, P <0.05) to young levels (Old-GCV vs. young-vehicle, P =0.98), and EDD was higher in old C57BL/6N mice treated with ABT-263 vs. vehicle (96±1% vs. 82±3%, P <0.05). Improvements in endothelial function were mediated by increased nitric oxide (NO) bioavailability ( P <0.05) and reduced oxidative stress ( P <0.05). Circulating SASP factors related to NO signaling were associated with greater NO-mediated EDD following senescent cell clearance. CONCLUSIONS: Cellular senescence and the SASP contribute to vascular aging and senolytics hold promise for improving age-related vascular function.
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scRNA-seq data of all aortic cells point to a role of senescent VSMCs in ECM remodeling and organization, consistent with Clayton et al.
“However, the scRNA-seq data of all aortic cells point to a role of senescent VSMCs in ECM remodeling and organization, consistent with the findings of Clayton et al.47”
From Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice (2025) · cites this paper as [47]
The Discussion (page unavailable) links cellular senescence to age-related changes in the aortic extracellular matrix, and the aortic-stiffening results report reduced adventitial collagen after senescent-cell clearance. Those findings are consistent with a role in ECM remodeling, but Clayton et al. do not identify senescent VSMCs as the responsible cells. The scRNA-seq finding is the citing authors’ own, not a finding attributed to Clayton et al. (LLM, conf=0.88)
Experimental — accuracy not yet measuredA recent study attributed vascular stiffening to accumulation of senescent vascular cells in naturally aged mice.
“This finding is further supported by a recent study that attributed vascular stiffening to the accumulation of senescent vascular cells in naturally aged mice47.”
From Single-cell and spatial transcriptomics map senescent vascular cells in arterial remodeling during atherosclerosis in mice (2025) · cites this paper as [47]
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“70 Consistent with this concept, we observed a relation between NO-mediated EDD and SASP factors linked to sphingolipid biosynthesis, which governs NO production and degradation, as well as to NO signaling pathways.”
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BackgroundSelf-citationClayton, Z. S., Brunt, V. E., Hutton, D. A., VanDongen, N. S., D’Alessandro, A., Reisz, J. A., Ziemba, B. P., & Seals, D. R. (2020) · JACC CardioOncology · doi:10.1016/j.jaccao.2020.06.010 · Cited by 83 · cited 1× · see citing works
“20,46 TEMPOL administration to the vessel perfusate restored peak EDD selectively in old vehicle p16-3MR mice ( P 0.0001 with versus without TEMPOL) to levels not different ( P= 0.87) from young vehicle mice, without affecting EDD in the young vehicle animals.”
BackgroundInfluentialSelf-citationCdkn1a transcript variant 2 is a marker of aging and cellular senescence.
López-Domínguez, J. A., Rodríguez-López, S., Ahumada-Castro, U., Desprez, P.-Y., Konovalenko, M., Laberge, R.-M., Cárdenas, C., Villalba, J. M., & Campisi, J. (2021) · Aging · doi:10.18632/aging.203110 · Cited by 83 · cited 1× · see citing works
“13,26,27,29,30 However, the effects of ABT-263 on vascular dysfunction have not been determined.”
BackgroundSelf-citationAcklin, S., Zhang, M., Du, W., Zhao, X., Plotkin, M. D., Chang, J., Campisi, J., Zhou, D., & Xia, F. (2020) · Scientific Reports · doi:10.1038/s41598-020-71042-6 · Cited by 76 · cited 2× · see citing works
“27 This mouse model allows for selective genetic-based suppression of excess p16 INK4A -positive senescent cells with the antiviral drug GCV .”
BackgroundSelf-citationKim, H., Chang, J., Iyer, S., Han, L., Campisi, J., Manolagas, S. C., Zhou, D., & Almeida, M. (2019) · Aging Cell · doi:10.1111/acel.12923 · Cited by 74 · see citing works
Self-citationClayton, Z. S., Hutton, D. A., Brunt, V. E., VanDongen, N. S., Ziemba, B. P., Casso, A. G., Greenberg, N., Mercer, A. N., Rossman, M. J., Campisi, J., et al. (2021) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00118.2021 · Cited by 73 · see citing works
Self-citationLesniewski, L. A., Durrant, J., Connell, M., Folian, B. J., Donato, A. J., & Seals, D. R. (2011) · The Journals of Gerontology Series A · doi:10.1093/gerona/glq233 · Cited by 69 · cited 1× · see citing works
“20,49,50 Greater NADPH oxidase with aging was fully ameliorated by GCV treatment (old GCV versus old vehicle, P= 0.01; Figure 4C).”
MethodInfluentialSelf-citationGioscia‐Ryan, R. A., Clayton, Z. S., Zigler, M. C., Richey, J. J., Cuevas, L. M., Rossman, M. J., Battson, M. L., Ziemba, B. P., Hutton, D. A., VanDongen, N. S., et al. (2020) · The Journal of Physiology · doi:10.1113/jp280607 · Cited by 68 · cited 2× · see citing works
“20,21,31 Because there were no sex differences in our p16-3MR/ GCV study nor an influence of senescent cell clearance in young animals (young animals treated with ganciclo-vir), to reduce the overall number of mice used, we only studied old male mice for this study.”
BackgroundMethodSelf-citationLarge elastic artery stiffness with aging: novel translational mechanisms and interventions.
Fleenor, B. S. (2013) · Europe PMC (PubMed Central) · Cited by 63 · see citing works
Xin, M., Zhang, J., Block, E. R., & Patel, J. M. (2003) · Mechanisms of Ageing and Development · doi:10.1016/s0047-6374(03)00163-5 · Cited by 63 · cited 1× · see citing works
“53 Accordingly, we next aimed to identify potential SASP factors in the circulation related to cellular senescence-associated changes in NO-mediated EDD with aging.”
BackgroundExercise Counters the Age-Related Accumulation of Senescent Cells
Zhang, X., Englund, D. A., Aversa, Z., Jachim, S. K., White, T. A., & LeBrasseur, N. K. (2022) · Exercise and Sport Sciences Reviews · doi:10.1249/jes.0000000000000302 · Cited by 63 · cited 1× · see citing works
“15 As such, natural food-derived senolytic compounds (eg, fisetin 77 and grape-seed extract 78 ) and lifestyle strategies shown to reduce senescent cell burden (eg, aerobic exercise 79 ) represent viable avenues for overcoming current barriers to seno-lytic therapy for healthy vascular aging.”
BackgroundInorganic Nitrite Supplementation Improves Endothelial Function With Aging
Rossman, M. J., Gioscia‐Ryan, R. A., Santos‐Parker, J. R., Ziemba, B. P., Lubieniecki, K. L., Johnson, L. C., Poliektov, N. E., Bispham, N. Z., Woodward, K. A., Nagy, E., et al. (2021) · Hypertension · doi:10.1161/hypertensionaha.120.16175 · Cited by 46 · cited 1× · see citing works
“51,52 Furthermore, alterations in the circulating SASP can directly increase oxidative stress.”
BackgroundSelf-citationSenolysis induced by 25-hydroxycholesterol targets CRYAB in multiple cell types
Limbad, C., Doi, R., McGirr, J., Ciotlos, S., Pérez, K., Clayton, Z. S., Daya, R., Seals, D. R., Campisi, J., & Melov, S. (2022) · iScience · doi:10.1016/j.isci.2022.103848 · Cited by 46 · cited 1× · see citing works
“13,26,27,29,30 However, the effects of ABT-263 on vascular dysfunction have not been determined.”
BackgroundSelf-citationMeasuring Arterial Stiffness in Animal Experimental Studies
Butlin, M., Tan, I., Spronck, B., & Avolio, A. P. (2020) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.119.313861 · Cited by 43 · see citing works
Metabolomic signature of arterial stiffness in male patients with peripheral arterial disease
Zagura, M., Kals, J., Kilk, K., Serg, M., Kampus, P., Eha, J., Soomets, U., & Zilmer, M. (2015) · Hypertension Research · doi:10.1038/hr.2015.71 · Cited by 42 · cited 1× · see citing works
“64,65 Taken together, our findings suggest cellular senescence-associated changes in metabolism— toward a more glycolytic state—may alter the circulating SASP to promote aortic stiffening with aging.”
BackgroundClayton, Z. S., Brunt, V. E., Hutton, D. A., Casso, A. G., Ziemba, B. P., Melov, S., Campisi, J., & Seals, D. R. (2021) · Hypertension · doi:10.1161/hypertensionaha.120.16759 · Cited by 40 · see citing works
Self-citationAssociation of Aortic Stiffness and Cognitive Decline: A Systematic Review and Meta-Analysis
Liu, Q., Fang, J., Cui, C., Dong, S., Gao, L., Bao, J., Li, Y., Ma, M., Chen, N., & He, L. (2021) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2021.680205 · Cited by 37 · cited 1× · see citing works
“58 It is important to understand the mechanism(s) mediating arterial stiffening with aging, as these mechanism(s) could serve as viable therapeutic targets for treatments.”
BackgroundCasso, A. G., VanDongen, N. S., Gioscia‐Ryan, R. A., Clayton, Z. S., Greenberg, N., Ziemba, B. P., Hutton, D. A., Neilson, A. P., Davy, K. P., Seals, D. R., et al. (2022) · The Journal of Physiology · doi:10.1113/jp283581 · Cited by 31 · see citing works
Self-citationNitric oxide and sphingolipids: mechanisms of interaction and role in cellular pathophysiology
Perrotta, C., Palma, C. D., & Clementi, E. (2008) · Biological Chemistry · doi:10.1515/bc.2008.155 · Cited by 27 · cited 1× · see citing works
“71 We also observed a relation between SASP factors related to oxidative stress (eg, altered glutathione metabolism) and NO-mediated EDD, suggesting the SASP may contribute to endothelial dysfunction by promoting excessive superoxide-related scavenging of NO.”
BackgroundThe Putative Role of Methylglyoxal in Arterial Stiffening: A Review
van der Bruggen, M. M., Spronck, B., Delhaas, T., Reesink, K. D., & Schalkwijk, C. G. (2021) · Heart Lung and Circulation · doi:10.1016/j.hlc.2021.06.527 · Cited by 27 · cited 1× · see citing works
“64,65 Taken together, our findings suggest cellular senescence-associated changes in metabolism— toward a more glycolytic state—may alter the circulating SASP to promote aortic stiffening with aging.”
BackgroundKuehnemann, C., Hughes, J. B., Desprez, P., Melov, S., Wiley, C. D., & Campisi, J. (2022) · Aging Cell · doi:10.1111/acel.13750 · Cited by 27 · cited 1× · see citing works
“5,6 Senescent cells alter the circulating milieu (eg, plasma) by secreting numerous proinflammatory cytokines, chemokines, metabolites, and growth factors termed the senescence-associated secretory phenotype (SASP), which can induce oxidative stress.”
BackgroundSelf-citationGioscia‐Ryan, R. A., Clayton, Z. S., Fleenor, B. S., Eng, J. S., Johnson, L. C., Rossman, M. J., Zigler, M. C., Evans, T. D., & Seals, D. R. (2020) · GeroScience · doi:10.1007/s11357-020-00212-1 · Cited by 25 · cited 1× · see citing works
“20,21,31 Because there were no sex differences in our p16-3MR/ GCV study nor an influence of senescent cell clearance in young animals (young animals treated with ganciclo-vir), to reduce the overall number of mice used, we only studied old male mice for this study.”
BackgroundSelf-citationLarge Artery Stiffness: A Companion to the 2015 AHA Science Statement on Arterial Stiffness
Rey-García, J., & Townsend, R. R. (2021) · Pulse · doi:10.1159/000518613 · Cited by 17 · cited 4× · see citing works
“Here, we demonstrate the role of cellular senescence and the circulating SASP in mediating age-related large elastic artery stiffness, as assessed via aortic PWV, and endothelial dysfunction, determined by carotid artery EDD.”
BackgroundInfluentialNishiuchi, S., Yagi, K., Saito, H., Zamami, Y., Niimura, T., Miyata, K., Sakamoto, Y., Fukunaga, K., Ishida, S., Hamano, H., et al. (2022) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2022.175083 · Cited by 15 · cited 1× · see citing works
“Aortic p16 INK4A abundance and BCL-2 activity, assessed as BAX/ BCL-2 protein abundance, 32,33”
BackgroundNovel Murine Biomarkers of Radiation Exposure Using An Aptamer-Based Proteomic Technology
Sproull, M. T., Shankavaram, U. T., & Camphausen, K. A. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.633131 · Cited by 12 · cited 1× · see citing works
“41,42 Most differences in individual plasma proteins were modest, with only a few significantly altered at a false discovery rate of P 0.01 (Figure 2C).”
BackgroundInfluential
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Mahoney, S. A., Venkatasubramanian, R., Darrah, M. A., Ludwig, K. R., VanDongen, N. S., Greenberg, N., Longtine, A. G., Hutton, D. A., Brunt, V. E., Campisi, J., et al. (2023) · Aging Cell · doi:10.1111/acel.14060 · Cited by 107 · see citing works
“Leveraging genetic senolysis models in combination with senolytic agents is considered the reference standard for assessing the causal impact of cellular senescence on physiological function (Clayton et al., 2023; Demaria et al., 2014, 2017 ).”
BackgroundInfluentialSelf-citationCurrent senolytics: Mode of action, efficacy and limitations, and their future
Rad, A. N., & Grillari, J. (2023) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2023.111888 · Cited by 86 · see citing works
The brain–body energy conservation model of aging
Shaulson, E. D., Cohen, A. A., & Picard, M. A. (2024) · Nature Aging · doi:10.1038/s43587-024-00716-x · Cited by 76 · see citing works
“…levels in depigmented human hair shafts 215 Fibrosis Proliferation of fibroblasts and undesirable excessive secretion of extracellular matrix 216 Transformation of tissue characteristics to maintain soft tissue tone (for example, vascular) at a minimal energetic cost by reducing the need…”
The Multifaceted Role of Endothelial Sirt1 in Vascular Aging: An Update
Campagna, R., Mazzanti, L., Pompei, V., Alia, S., Vignini, A., & Emanuelli, M. (2024) · Cells · doi:10.3390/cells13171469 · Cited by 57 · see citing works
“…cells that have become senescent arrest the cell cycle preventing further divisions and acquire typical phenotypic traits causing impairment of the angiogenic process, vascular inflammation, and remodeling, and display increased levels of ROS and a decreased NO bioavailability [144,155,156].”
BackgroundOxidative stress and cell senescence as drivers of ageing: Chicken and egg
von Zglinicki, T. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102558 · Cited by 52 · see citing works
Mazan-Mamczarz, K., Tsitsipatis, D., Childs, B. G., Carr, A. E., Dos Santos, C. R., Anerillas, C., Romero, B., Gregg, J. M., Henry-Smith, C., Okereke, A. N., et al. (2025) · Nature Aging · doi:10.1038/s43587-025-00889-z · Cited by 37 · see citing works
“This finding is further supported by a recent study that attributed vascular stiffening to the accumulation of senescent vascular cells in naturally aged mice 47 .”
Anti-ageing interventions for the treatment of cardiovascular disease
Abdellatif, M., Schmid, S., Fuerlinger, A., & Kroemer, G. (2024) · Cardiovascular Research · doi:10.1093/cvr/cvae177 · Cited by 41 · see citing works
“164 Similarly, fisetin, a naturally occurring senotherapeutic flavonoid, 165 improved vascular stiffness and endothelial function in old female and male mice by reducing oxidative stress and increasing NO bioavailability.”
Cyclic nucleotide phosphodiesterases as drug targets
Kelly, M. P., Nikolaev, V. O., Gobejishvili, L., Lugnier, C., Heßlinger, C., Nickolaus, P., Kass, D. A., de Vasconcelos, W. P., Fischmeister, R., Brocke, S., et al. (2025) · Pharmacological Reviews · doi:10.1016/j.pharmr.2025.100042 · Cited by 38 · see citing works
Balasubramanian, P., Kiss, T., Gulej, R., Toth, A. N., Tarantini, S., Yabluchanskiy, A., Ungvari, Z. I., & Csiszár, A. (2024) · Nutrients · doi:10.3390/nu16070952 · Cited by 33 · see citing works
“These mice express the 3MR transgene construct containing luciferase, red fluorescent protein, and thymidine kinase under the control of p16 promoter [120–128].”
BackgroundPharmacological modulation of vascular ageing: A review from VascAgeNet
Roth, L., Doğan, S., Tuna, B. G., Arányi, T., Benı́tez, S., Borrell-Pagés, M., Bozaykut, P., Meyer, G. R. Y. D., Duca, L., Durmuş, N., et al. (2023) · Ageing Research Reviews · doi:10.1016/j.arr.2023.102122 · Cited by 36 · see citing works
Sutanto, H., Fetarayani, D., Narendra, M. R., & Nasution, S. A. (2025) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2025.106488 · Cited by 30 · see citing works
“In aged vessels, the accumulation of senescent endothelial cells, VSMCs, and adventitial fibroblasts leads to a continuous release of SASP factors, which remodel the vascular ECM, compromise vascular tone, and initiate atherogenic signaling cascades [68,69].”
Perivascular fat tissue and vascular aging: A sword and a shield
Wang, Y., Wang, X., chen, Y., Zhang, Y., Zhen, X., Tao, S., Dou, J., Li, P., & Jiang, G. (2024) · Pharmacological Research · doi:10.1016/j.phrs.2024.107140 · Cited by 23 · see citing works
Oxysterol Sensing Through GPR183 Triggers Endothelial Senescence in Hypertension
Chu, Q., Li, Y., Wu, J., Gao, Y., Xiangyun, G., Li, J., Lv, H., Liu, M., Tang, W., Zhan, P., et al. (2024) · Circulation Research · doi:10.1161/circresaha.124.324722 · Cited by 23 · see citing works
“19,20 Therefore, a comprehensive identification of potential targets will accelerate the development of strategies to attenuate endothelial senescence and improve vascular disease outcomes.”
Ungvari, A., Gulej, R., Patai, R., Papp, Z., Tóth, A., Szabó, A. Á., Podesser, B. K., Sótonyi, P., Benyó, Z., Yabluchanskiy, A., et al. (2025) · GeroScience · doi:10.1007/s11357-024-01489-2 · Cited by 21 · see citing works
“Current research in senolytic agents has shown promise in preclinical models, including the potential to restore endothelial function [184, 186, 190, 201, 207, 220], rescue the integrity of the blood–brain barrier [115, 207], and prevent cerebral microhemorrhages [188].”
InfluentialCardiovascular ageing: hallmarks, signaling pathways, diseases and therapeutic targets
Zheng, P., Yan, W., Ding, Y.-N., Zhang, Y., Chen, Z., Qian, J., & Ge, J. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02630-7 · Cited by 26 · see citing works
“254 Recent fi ndings highlight the signi fi cance of EC senescence: impaired glucose transport is associated with cardiac EC senescence 255 ; a glycolytic shift promotes vascular senescence, an effect reversible by senolytics 256 ; and evidence suggests reduced lactate production in senescent ECs.”
Cellular elasticity in cancer: a review of altered biomechanical features
Radman, B. A., Alhameed, A. M. M., Shu, G., Yin, G., & Wang, M. (2024) · Journal of Materials Chemistry B · doi:10.1039/d4tb00328d · Cited by 22 · see citing works
Targeting vascular senescence in cardiovascular disease with aging
Hall, S. A., & Lesniewski, L. A. (2024) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2023.45 · Cited by 25 · see citing works
“Additionally, a reduction in circulating SASP factors in concert with NO signaling was associated with enhanced NO-mediated EDD subsequent to the removal of senescent cells in both treatment groups [85] .”
BackgroundInfluentialMurray, K. O., Mahoney, S. A., Ludwig, K. R., Miyamoto-Ditmon, J., VanDongen, N. S., Banskota, N., Herman, A. B., Seals, D. R., Mankowski, R. T., Rossman, M. J., et al. (2025) · Aging Cell · doi:10.1111/acel.70114 · Cited by 19 · see citing works
Self-citationMahoney, S. A., Dey, A. K., Basisty, N., & Herman, A. B. (2023) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00352.2023 · Cited by 20 · see citing works
Self-citationSenolytic therapies for cardiovascular aging: tackling fibrosis and metabolic dysfunction
Atlante, S., Zamperla, M. G., Cis, L., Farsetti, A., & Gaetano, C. (2025) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2025.07.009 · Cited by 19 · see citing works
Exercise to Prevent Accelerated Vascular Aging in People Living With HIV
Jones, R., Robinson, A. T., Beach, L. B., Lindsey, M. L., Kirabo, A., Hinton, A. O., Jr., Erlandson, K. M., & Jenkins, N. D. M. (2024) · Circulation Research · doi:10.1161/circresaha.124.323975 · Cited by 22 · see citing works
SIRT3-Mediated Mitochondrial Regulation and Driver Tissues in Systemic Aging
Šešelja, K., Šimunić, E., Sobočanec, S., Podgorski, I. I., Pinterić, M., Hadžija, M. P., Balog, T., & Belužić, R. (2025) · Genes · doi:10.3390/genes16121497 · Cited by 18 · see citing works
“Locally, accumulated senescent fibroblasts and endothelial cells contribute to extracellular matrix degradation and vascular stiffening, while senescent immune cells impair immune surveillance, amplifying low-grade inflammaging [52,53].”
Guduric‐Fuchs, J., Pedrini, E., Bertelli, P. M., McDonnell, S., Pathak, V., McLoughlin, K. J., O’Neill, C. L., Stitt, A. W., & Medina, R. J. (2024) · Aging Cell · doi:10.1111/acel.14240 · Cited by 16 · see citing works
“Furthermore, aged mouse treated with senolytic ABT-263 showed reduced aortic stiffness and improved endothelial function mediated by SASP modulation (Clayton et al., 2023).”
BackgroundShafqat, A., Masters, M. C., Tripathi, U., Tchkonia, T., Kirkland, J. L., & Hashmi, S. K. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102400 · Cited by 15 · see citing works
Testosterone deficiency promotes arterial stiffening independent of sex chromosome complement
Sakamuri, A., Visniauskas, B., Kilanowski‐Doroh, I., McNally, A. B., Sugi, A. I., Kamau, A., Sengottaian, D., McLachlan, J. A., Anguera, M. C., Mauvais‐Jarvis, F., et al. (2024) · Biology of Sex Differences · doi:10.1186/s13293-024-00624-0 · Cited by 14 · see citing works
“Our data shows that carotid walls got thinner while the aorta wall had an increase in collagen deposition, suggesting higher mechanical wall stress associated with aging and hypertension [48, 53].”
Russo, L., Babboni, S., Andreassi, M. G., Daher, J., Canale, P., Turco, S. D., & Basta, G. (2025) · Antioxidants · doi:10.3390/antiox14010099 · Cited by 15 · see citing works
Mechanisms of cellular senescence-induced vascular aging: evidence of senotherapeutic strategies
Mahoney, S. A., Bloom, S. I., Seals, D. R., Donato, A. J., Rossman, M. J., & Clayton, Z. S. (2025) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2024.31 · Cited by 15 · see citing works
“…blood exchange (administration of blood/ blood factors of one organism into the circulating milieu of another organism) [67] , and in vitro or ex vivo exposure of cells [68,69] or organ systems [13,70] , respectively, to distinct components of the circulation (e.g., blood/plasma/serum).”
InfluentialSelf-citationSex, senescence, senolytics, and cognition
Foster, T. C., & Kumar, A. (2025) · Frontiers in Aging Neuroscience · doi:10.3389/fnagi.2025.1555872 · Cited by 13 · see citing works
PAI-1 is a common driver of aging and diverse diseases
Khoddam, A., Miyata, T., & Vaughan, D. E. (2025) · Biomedical Journal · doi:10.1016/j.bj.2025.100892 · Cited by 12 · see citing works
“Together with PAI-1 as a component of SASP, accumulation of senescent cells along the vasculature contribute to the arterial pathophysiology seen in advanced age [61].”
Cellular and molecular mechanisms underlying cardiovascular aging
Zhang, S.-Y., Yang, Y., Wen, R., Yang, N., Feng, S., & Zhang, T. (2025) · Cellular & Molecular Biology Letters · doi:10.1186/s11658-025-00803-w · Cited by 12 · see citing works
“Recent research has emphasized the critical role of endothelial senescence in the pathogenesis of hypertension and age-associated vascular diseases [73, 74].”
Role of the circulating milieu in age-related arterial dysfunction: a novel ex vivo approach
Mahoney, S. A., VanDongen, N. S., Greenberg, N., Venkatasubramanian, R., Rossman, M. J., Widlansky, M. E., Brunt, V. E., de Quirós, Y. B., Seals, D. R., & Clayton, Z. S. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00014.2024 · Cited by 12 · see citing works
Self-citationPeripheral vascular dysfunction and the aging brain
Wahl, D., & Clayton, Z. S. (2024) · Aging · doi:10.18632/aging.205877 · Cited by 12 · see citing works
Self-citationStepanov, A. D., Shishkova, D. K., Markova, V. E., Markova, Y. O., Frolov, A. V., Lazebnaya, A. A., Oshchepkova, K., Perepletchikova, D. A., Smirnova, D., Basovich, L., et al. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms252111382 · Cited by 11 · see citing works
Lambert, M., Miquel, G., Villeneuve, L. R., Thorin‐Trescases, N., & Thorin, É. (2025) · GeroScience · doi:10.1007/s11357-025-01563-3 · Cited by 11 · see citing works
Venkatasubramanian, R., Mahoney, S. A., Hutton, D. A., VanDongen, N. S., Brunt, V. E., Greenberg, N., Longtine, A. G., Brandt, L., Beyer, A., Melov, S., et al. (2025) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00712.2025 · Cited by 11 · see citing works
Self-citationAging of the Hematopoietic System: Mechanisms, Consequences, and Systemic Interactions
Miyawaki, M., Hashimoto, S., Ogawa, S., & Kase, Y. (2026) · Aging Cell · doi:10.1111/acel.70385 · Cited by 10 · see citing works
Darvish, S., Mahoney, S. A., Venkatasubramanian, R., Rossman, M. J., Clayton, Z. S., & Murray, K. O. (2024) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00188.2024 · Cited by 10 · see citing works
Self-citationPower, G. J., Lateef, O. M., Ramirez‐Perez, F. I., Lazo‐Fernandez, Y., Augenreich, M. A., Ferreira‐Santos, L., Soares, R. N., Gonzalez-Vallejo, J. D., Morales‐Quinones, M., Norton, C. E., et al. (2024) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00667.2024 · Cited by 9 · see citing works
Endothelial cell senescence and mitochondrial dysfunction in vascular ageing
Walczak, I., Tarnawska, M., Stawarska, K., Braczko, A., Paterek, A., Rolski, F., Leszek, P., Smolarek, D., Kapusta, M., Narajczyk, M., et al. (2026) · Ageing Research Reviews · doi:10.1016/j.arr.2026.103119 · Cited by 10 · see citing works
Mahoney, S. A., Mazan-Mamczarz, K., Tsitsipatis, D., VanDongen, N. S., Henry-Smith, C., Okereke, A. N., Munk, R. B., Darvish, S., Murray, K. O., De, S., et al. (2026) · Aging Cell · doi:10.1111/acel.70500 · Cited by 9 · see citing works
Self-citationSingh, P., Venkatasubramanian, R., Mahoney, S. A., Darrah, M. A., Ludwig, K. R., Zhang, A., Kaneshiro, K. R., Najera, L. E., Wimer, L. A., Shanmugam, M. M., et al. (2025) · Aging · doi:10.18632/aging.206335 · Cited by 8 · see citing works
“Together, these findings are consistent with our previous observations of lower NO production in senescent endothelial cells [15] and further confirm the senescence-inducing effects of MGO-induced glycation stress, and protective effects of Gly-Low on endothelial cell senescence-related phenotypes.”
InfluentialSelf-citationTan, S., Nepovimová, E., Valko, M., Jomová, K., Wu, Q., & Kuča, K. (2026) · Cell Communication and Signaling · doi:10.1186/s12964-026-02855-7 · Cited by 10 · see citing works
Insights into the therapeutic strategies for aging and aging-associated diseases
Dong, R., Wu, Q., Kan, J., Fu, C., Sorrentino, V., Chow, A., Lei, Y., Wu, D., Xu, Z., Du, J., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02662-z · Cited by 9 · see citing works
Venkatasubramanian, R., Darrah, M., Mahoney, S. A., Hutton, D. A., Maurer, G. S., Ludwig, K. R., VanDongen, N. S., Greenberg, N., Longtine, A. G., Brunt, V. E., et al. (2025) · Hypertension · doi:10.1161/hypertensionaha.125.25408 · Cited by 7 · see citing works
Self-citationMicrovascular Health as a Key Determinant of Organismal Aging
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- Authors
- Clayton, Z. S., Rossman, M. J., Mahoney, S. A., Venkatasubramanian, R., Maurer, G. S., Hutton, D. A., VanDongen, N. S., Greenberg, N. T., Longtine, A. G., Ludwig, K. R., Brunt, V. E., LaRocca, T. J., Campisi, J., Melov, S., & Seals, D. R.
- Affiliations
- University of Colorado Boulder (US)
- Colorado State University (US)
- Buck Institute for Research on Aging (US)
- ORCID
- Venue
- Hypertension
- Published
- 2023-10
- Volume
- 80
- Issue
- 10
- Pages
- 2072-2087
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- PMC
- PMC10530538
- OpenAlex
- W4385969491
- Cited by
- 84
- References
- 79
- Citations by year
- 2026: 29 · 2025: 25 · 2024: 25 · 2023: 5
- FWCI
- 14.84
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Aging (R01AG055822)
- National Heart, Lung, and Blood Institute (K99HL159241, F32HL151022, F31HL165885)
- National Institute of Diabetes and Digestive and Kidney Diseases (K01DK115524, T32DK007135)
- Topics
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Aging › Genetics, Aging, and Longevity in Model Organisms
- Keywords
- ENCE, senolytics, senescence-associated secretory phenotype, aortic stiffness, endothelial dysfunction, aging, ganciclovir, navitoclax, pulse wave velocity, nitric oxide bioavailability, oxidative stress, endothelium-dependent dilation, glycolysis
- MeSH terms
- Senotherapeutics, Aging, Aniline Compounds, Animals, Arteries, Mice, Inbred C57BL, Nitric Oxide, Sulfonamides, Vascular Diseases, Cellular Senescence, Mice, Pulse Wave Analysis
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