REFERENCES
1. Timmis A, Townsend N, Gale C, et al. ESC Scientific Document Group. European society of cardiology: cardiovascular disease statistics 2017. Eur Heart J 2018;39:508-79.
2. McDonagh TA, Metra M, Adamo M, et al. ESC Scientific Document Group. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J 2021;42:3599-726.
3. Argulian E, Chandrashekhar Y, Shah SJ, et al. Teasing apart heart failure with preserved ejection fraction phenotypes with echocardiographic imaging: potential approach to research and clinical practice. Circ Res 2018;122:23-5.
5. Steffens S, Nahrendorf M, Madonna R. Immune cells in cardiac homeostasis and disease: emerging insights from novel technologies. Eur Heart J ;2021:ehab842.
6. Muñoz-Espín D, Serrano M. Cellular senescence: from physiology to pathology. Nat Rev Mol Cell Biol 2014;15:482-96.
7. Kuilman T, Peeper DS. Senescence-messaging secretome: SMS-ing cellular stress. Nat Rev Cancer 2009;9:81-94.
8. Kuilman T, Michaloglou C, Mooi WJ, Peeper DS. The essence of senescence. Genes Dev 2010;24:2463-79.
9. Ruiz-Meana M, Bou-Teen D, Ferdinandy P, et al. Cardiomyocyte ageing and cardioprotection: consensus document from the ESC working groups cell biology of the heart and myocardial function. Cardiovasc Res 2020;116:1835-49.
10. Souders CA, Bowers SL, Baudino TA. Cardiac fibroblast: the renaissance cell. Circ Res 2009;105:1164-76.
11. Pittenger MF, Mackay AM, Beck SC, et al. Multilineage potential of adult human mesenchymal stem cells. Science 1999;284:143-7.
13. Reus TL, Robert AW, Da Costa MB, de Aguiar AM, Stimamiglio MA. Secretome from resident cardiac stromal cells stimulates proliferation, cardiomyogenesis and angiogenesis of progenitor cells. Int J Cardiol 2016;221:396-403.
14. Madonna R, Guarnieri S, Kovácsházi C, et al. Telomerase/myocardin expressing mesenchymal cells induce survival and cardiovascular markers in cardiac stromal cells undergoing ischaemia/reperfusion. J Cell Mol Med 2021;25:5381-90.
15. Limana F, Capogrossi MC, Germani A. The epicardium in cardiac repair: from the stem cell view. Pharmacol Ther 2011;129:82-96.
16. Forbes SJ, Rosenthal N. Preparing the ground for tissue regeneration: from mechanism to therapy. Nat Med 2014;20:857-69.
17. Mayourian J, Ceholski DK, Gonzalez DM, et al. Physiologic, pathologic, and therapeutic paracrine modulation of cardiac excitation-contraction coupling. Circ Res 2018;122:167-83.
18. Eschenhagen T, Bolli R, Braun T, et al. Cardiomyocyte regeneration: a consensus statement. Circulation 2017;136:680-6.
19. Galli D, Innocenzi A, Staszewsky L, et al. Mesoangioblasts, vessel-associated multipotent stem cells, repair the infarcted heart by multiple cellular mechanisms: a comparison with bone marrow progenitors, fibroblasts, and endothelial cells. Arterioscler Thromb Vasc Biol 2005;25:692-7.
20. Traktuev DO, Merfeld-Clauss S, Li J, et al. A population of multipotent CD34-positive adipose stromal cells share pericyte and mesenchymal surface markers, reside in a periendothelial location, and stabilize endothelial networks. Circ Res 2008;102:77-85.
22. Sommariva E, Brambilla S, Carbucicchio C, et al. Cardiac mesenchymal stromal cells are a source of adipocytes in arrhythmogenic cardiomyopathy. Eur Heart J 2016;37:1835-46.
23. Stadiotti I, Piacentini L, Vavassori C, et al. Human cardiac mesenchymal stromal cells from right and left ventricles display differences in number, function, and transcriptomic profile. Front Physiol 2020;11:604.
24. Amendola A, Garoffolo G, Songia P, et al. Human cardiosphere-derived stromal cells exposed to SARS-CoV-2 evolve into hyper-inflammatory/pro-fibrotic phenotype and produce infective viral particles depending on the levels of ACE2 receptor expression. Cardiovasc Res 2021;117:1557-66.
25. Rotini A, Martínez-Sarrà E, Duelen R, et al. Aging affects the in vivo regenerative potential of human mesoangioblasts. Aging Cell 2018;17:e12714.
26. Perkisas S, Vandewoude M. Where frailty meets diabetes. Diabetes Metab Res Rev 2016;32 Suppl 1:261-7.
27. Palmer AK, Tchkonia T, LeBrasseur NK, Chini EN, Xu M, Kirkland JL. Cellular senescence in type 2 diabetes: a therapeutic opportunity. Diabetes 2015;64:2289-98.
28. Sloth AD, Schmidt MR, Munk K, et al. CONDI Investigators. Impact of cardiovascular risk factors and medication use on the efficacy of remote ischaemic conditioning: post hoc subgroup analysis of a randomised controlled trial. BMJ Open 2015;5:e006923.
29. Persson F, Nyström T, Jørgensen ME, et al. Dapagliflozin is associated with lower risk of cardiovascular events and all-cause mortality in people with type 2 diabetes (CVD-REAL Nordic) when compared with dipeptidyl peptidase-4 inhibitor therapy: a multinational observational study. Diabetes Obes Metab 2018;20:344-51.
30. Zinman B, Wanner C, Lachin JM, et al. EMPA-REG OUTCOME Investigators. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med 2015;373:2117-28.
31. Cahn A, Mosenzon O, Wiviott SD, et al. Efficacy and safety of dapagliflozin in the elderly: analysis from the DECLARE-TIMI 58 study. Diabetes Care 2020;43:468-75.
32. Leiter LA, Cefalu WT, de Bruin TW, Gause-Nilsson I, Sugg J, Parikh SJ. Dapagliflozin added to usual care in individuals with type 2 diabetes mellitus with preexisting cardiovascular disease: a 24-week, multicenter, randomized, double-blind, placebo-controlled study with a 28-week extension. J Am Geriatr Soc 2014;62:1252-62.
33. Madonna R, Doria V, Minnucci I, Pucci A, Pierdomenico DS, De Caterina R. Empagliflozin reduces the senescence of cardiac stromal cells and improves cardiac function in a murine model of diabetes. J Cell Mol Med 2020;24:12331-40.
34. Maly K, Strese K, Kampfer S, et al. Critical role of protein kinase C α and calcium in growth factor induced activation of the Na+/H+ exchanger NHE1. FEBS Letters 2002;521:205-10.
35. Katare R, Caporali A, Zentilin L, et al. Intravenous gene therapy with PIM-1 via a cardiotropic viral vector halts the progression of diabetic cardiomyopathy through promotion of prosurvival signaling. Circ Res 2011;108:1238-51.
36. Madonna R, Pieragostino D, Rossi C, et al. Transplantation of telomerase/myocardin-co-expressing mesenchymal cells in the mouse promotes myocardial revascularization and tissue repair. Vascul Pharmacol 2020;135:106807.
37. Madonna R, Taylor DA, Geng YJ, et al. Transplantation of mesenchymal cells rejuvenated by the overexpression of telomerase and myocardin promotes revascularization and tissue repair in a murine model of hindlimb ischemia. Circ Res 2013;113:902-14.
38. Madonna R, Willerson JT, Geng YJ. Myocardin a enhances telomerase activities in adipose tissue mesenchymal cells and embryonic stem cells undergoing cardiovascular myogenic differentiation. Stem Cells 2008;26:202-11.
40. Baker DJ, Childs BG, Durik M, et al. Naturally occurring p16(Ink4a)-positive cells shorten healthy lifespan. Nature 2016;530:184-9.
41. 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.
42. Balistreri CR, Madonna R, Ferdinandy P. Is it the time of seno-therapeutics application in cardiovascular pathological conditions related to ageing? Curr Res Pharmacol Drug Discov 2021;2:100027.
43. Gale CP, Cattle BA, Woolston A, et al. Resolving inequalities in care? Eur Heart J 2012;33:630-9.
44. Perrino C, Barabási AL, Condorelli G, et al. Epigenomic and transcriptomic approaches in the post-genomic era: path to novel targets for diagnosis and therapy of the ischaemic heart? Cardiovasc Res 2017;113:725-36.
45. Hacker TA, McKiernan SH, Douglas PS, Wanagat J, Aiken JM. Age-related changes in cardiac structure and function in Fischer 344 x Brown Norway hybrid rats. Am J Physiol Heart Circ Physiol 2006;290:H304-11.
46. Lesnefsky EJ, Chen Q, Hoppel CL. Mitochondrial metabolism in aging heart. Circ Res 2016;118:1593-611.
47. Madonna R, De Caterina R, Willerson JT, Geng YJ. Biologic function and clinical potential of telomerase and associated proteins in cardiovascular tissue repair and regeneration. Eur Heart J 2011;32:1190-6.
48. Cai Y, Liu H, Song E, et al. Deficiency of telomere-associated repressor activator protein 1 precipitates cardiac aging in mice via p53/PPARα signaling. Theranostics 2021;11:4710-27.
49. Liochev SI. Reactive oxygen species and the free radical theory of aging. Free Radic Biol Med 2013;60:1-4.
50. Häseli S, Deubel S, Jung T, Grune T, Ott C. Cardiomyocyte contractility and autophagy in a premature senescence model of cardiac aging. Oxid Med Cell Longev 2020;2020:8141307.
51. Moscato S, Cabiati M, Bianchi F, et al. Heart and liver connexin expression related to the first stage of aging: a study on naturally aged animals. Acta Histochem 2020;122:151651.
52. Ma Y, Li J. . Metabolic shifts during aging and pathology. In: Terjung R, editor. Comprehensive Physiology. Wiley; 2011. p. 667-86.
53. Coppé JP, Patil CK, Rodier F, et al. Senescence-associated secretory phenotypes reveal cell-nonautonomous functions of oncogenic RAS and the p53 tumor suppressor. PLoS Biol 2008;6:2853-68.
54. Ren J, Sowers JR, Zhang Y. Metabolic stress, autophagy, and cardiovascular aging: from pathophysiology to therapeutics. Trends Endocrinol Metab 2018;29:699-711.
55. Mouton RE, Venable ME. Ceramide induces expression of the senescence histochemical marker, β-galactosidase, in human fibroblasts. Mech Ageing Dev 2000;113:169-81.
56. Tran D, Bergholz J, Zhang H, et al. Insulin-like growth factor-1 regulates the SIRT1-p53 pathway in cellular senescence. Aging Cell 2014;13:669-78.
57. Kim KS, Seu YB, Baek SH, et al. Induction of cellular senescence by insulin-like growth factor binding protein-5 through a p53-dependent mechanism. Mol Biol Cell 2007;18:4543-52.
58. Davalos AR, Kawahara M, Malhotra GK, et al. p53-dependent release of Alarmin HMGB1 is a central mediator of senescent phenotypes. J Cell Biol 2013;201:613-29.
59. Kim CS, Park HS, Kawada T, et al. Circulating levels of MCP-1 and IL-8 are elevated in human obese subjects and associated with obesity-related parameters. Int J Obes (Lond) 2006;30:1347-55.
60. Elzi DJ, Lai Y, Song M, Hakala K, Weintraub ST, Shiio Y. Plasminogen activator inhibitor 1--insulin-like growth factor binding protein 3 cascade regulates stress-induced senescence. Proc Natl Acad Sci U S A 2012;109:12052-7.
61. Shakeri H, Lemmens K, Gevaert AB, De Meyer GRY, Segers VFM. Cellular senescence links aging and diabetes in cardiovascular disease. Am J Physiol Heart Circ Physiol 2018;315:H448-62.
62. 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.
63. 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.
64. Walaszczyk A, Dookun E, Redgrave R, et al. Pharmacological clearance of senescent cells improves survival and recovery in aged mice following acute myocardial infarction. Aging Cell 2019;18:e12945.
65. Guerrero A, Herranz N, Sun B, et al. Cardiac glycosides are broad-spectrum senolytics. Nat Metab 2019;1:1074-88.
66. Lazaro I, Oguiza A, Recio C, et al. Targeting HSP90 ameliorates nephropathy and atherosclerosis through suppression of NF-κB and STAT signaling pathways in diabetic mice. Diabetes 2015;64:3600-13.
67. Mattison JA, Wang M, Bernier M, et al. Resveratrol prevents high fat/sucrose diet-induced central arterial wall inflammation and stiffening in nonhuman primates. Cell Metab 2014;20:183-90.
68. Gao D, Zuo Z, Tian J, et al. Activation of SIRT1 attenuates klotho deficiency-induced arterial stiffness and hypertension by enhancing AMP-activated protein kinase activity. Hypertension 2016;68:1191-9.
69. Liu Y, Wang TT, Zhang R, et al. Calorie restriction protects against experimental abdominal aortic aneurysms in mice. J Exp Med 2016;213:2473-88.
70. Werner C, Gensch C, Pöss J, Haendeler J, Böhm M, Laufs U. Pioglitazone activates aortic telomerase and prevents stress-induced endothelial apoptosis. Atherosclerosis 2011;216:23-34.
71. Walters HE, Deneka-Hannemann S, Cox LS. Reversal of phenotypes of cellular senescence by pan-mTOR inhibition. Aging (Albany NY) 2016;8:231-44.
