REFERENCES

1. Li X, Pang X, Sun H, et al. Cardiac aging: molecular mechanisms and therapeutic interventions. Pharmacol Res. 2025;221:107954.

2. Ribeiro ASF, Zerolo BE, López-Espuela F, Sánchez R, Fernandes VS. Cardiac system during the aging process. Aging Dis. 2023;14:1105-22.

3. Haigis MC, Yankner BA. The aging stress response. Mol Cell. 2010;40:333-44.

4. Vetter VM, Drewelies J, Sommerer Y, et al. Epigenetic aging and perceived psychological stress in old age. Transl Psychiatry. 2022;12:410.

5. Gissler MC, Antiochos P, Ge Y, Heydari B, Gräni C, Kwong RY. Cardiac magnetic resonance evaluation of LV remodeling post-myocardial infarction: prognosis, monitoring and trial endpoints. JACC Cardiovasc Imaging. 2024;17:1366-80.

6. Leancă SA, Crișu D, Petriș AO, et al. Left ventricular remodeling after myocardial infarction: from physiopathology to treatment. Life. 2022;12:1111.

7. Subramanian V, Tucker WJ, Peters AE, Upadhya B, Kitzman DW, Pandey A. Cardiovascular aging and exercise: implications for heart failure prevention and management. Circ Res. 2025;137:205-30.

8. Cheng S, Fernandes VR, Bluemke DA, McClelland RL, Kronmal RA, Lima JA. Age-related left ventricular remodeling and associated risk for cardiovascular outcomes: the multi-ethnic study of atherosclerosis. Circ Cardiovasc Imaging. 2009;2:191-8.

9. Hernández-Vicente A, Hernando D, Santos-Lozano A, et al. Heart rate variability and exceptional longevity. Front Physiol. 2020;11:566399.

10. Zhao D, Wang Y, Wong ND, Wang J. Impact of aging on cardiovascular diseases: from chronological observation to biological insights: JACC family series. JACC Asia. 2024;4:345-58.

11. Tracy E, Rowe G, LeBlanc AJ. Cardiac tissue remodeling in healthy aging: the road to pathology. Am J Physiol Cell Physiol. 2020;319:C166-82.

12. Ingwall JS. Energy metabolism in heart failure and remodelling. Cardiovasc Res. 2009;81:412-9.

13. Li M, Fukagawa NK. Age-related changes in redox signaling and VSMC function. Antioxid Redox Signal. 2010;12:641-55.

14. Lakatta EG. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part III: cellular and molecular clues to heart and arterial aging. Circulation. 2003;107:490-7.

15. Janosevic D, Bertman K, Roth M, et al. Left ventricular concentric remodeling in normal aging is associated with decline of diastolic function assessed by multi-modality imaging. J Cardiovasc Magn Reson. 2011;13:1932.

16. Pillai R, Zhang L, Peters K, et al. Age- and sex-differences and reference values for ventricular strain by cardiovascular magnetic resonance imaging in adults without cardiovascular disease or cardiovascular disease risk factors. J Cardiovasc Magn Reson. 2025;27:101902.

17. Thomas JD, Edvardsen T, Abraham T, et al. Clinical applications of strain echocardiography: a clinical consensus statement from the American Society of Echocardiography Developed in collaboration with the European Association of Cardiovascular Imaging of the European Society of Cardiology. Eur Heart J Cardiovasc Imaging. 2026;27:335-68.

18. Kersten J, Hackenbroch C, Bouly M, Tyl B, Bernhardt P. What is normal for an aging heart? A Prospective CMR Cohort Study. J Cardiovasc Imaging. 2022;30:202-11.[DOI:10.4250/jcvi.2022. 0021].

19. Zhai P, Sung EA, Shiheido-Watanabe Y, Takayama K, Tian Y, Sadoshima J. Suppression of autophagy induces senescence in the heart. bioRxiv. 2024. 2024. Available from: https://www.biorxiv.org/content/10.1101/2024.05.26.595978v1.abstract [Last accessed on 28 May 2026].

20. Hu WS, Liao WY, Chang CH, Chen TS. Paracrine IGF-1 activates SOD2 expression and regulates ROS/p53 axis in the treatment of cardiac damage in D-galactose-induced aging rats after receiving mesenchymal stem cells. J Clin Med. 2022;11:4419.

21. Conte M, Petraglia L, Poggio P, et al. Inflammation and cardiovascular diseases in the elderly: the role of epicardial adipose tissue. Front Med. 2022;9:844266.

22. Loffredo FS, Steinhauser ML, Jay SM, et al. Growth differentiation factor 11 is a circulating factor that reverses age-related cardiac hypertrophy. Cell. 2013;153:828-39.

23. Egerman MA, Cadena SM, Gilbert JA, et al. GDF11 Increases with age and inhibits skeletal muscle regeneration. Cell Metab. 2015;22:164-74.

24. Kraler S, Balbi C, Vdovenko D, et al. Circulating GDF11 exacerbates myocardial injury in mice and associates with increased infarct size in humans. Cardiovasc Res. 2023;119:2729-42.

25. Ketchem JM, Bowman EJ, Isales CM. Male sex hormones, aging, and inflammation. Biogerontology. 2023;24:1-25.

26. Szabó R, Hoffmann A, Börzsei D, et al. Hormone replacement therapy and aging: a potential therapeutic approach for age-related oxidative stress and cardiac remodeling. Oxid Med Cell Longev. 2021;2021:8364297.

27. Morin-Grandmont A, Walsh-Wilkinson É, Labbé EA, et al. Biological sex, sex steroids and sex chromosomes contribute to mouse cardiac aging. Aging. 2024;16:7553-77.

28. Prud’homme GJ, Kurt M, Wang Q. Pathobiology of the klotho antiaging protein and therapeutic considerations. Front Aging. 2022;3:931331.

29. Chen K, Wang S, Sun QW, Zhang B, Ullah M, Sun Z. Correction to: klotho deficiency causes heart aging via impairing the Nrf2-GR pathway. Circ Res. 2025;137:e175.

30. Guo XH, Li YH, Zhao YS, Zhai YZ, Zhang LC. Antiaging effects of melatonin on the myocardial mitochondria of rats and associated mechanisms. Mol Med Rep. 2017;15:403-10.

31. Iacobellis G. Aging effects on epicardial adipose tissue. Front Aging. 2021;2:666260.

32. Vidal R, Wagner JUG, Braeuning C, et al. Transcriptional heterogeneity of fibroblasts is a hallmark of the aging heart. JCI Insight. 2019;4:131092.

33. Chang ACY, Pardon G, Chang ACH, et al. Increased tissue stiffness triggers contractile dysfunction and telomere shortening in dystrophic cardiomyocytes. Stem Cell Rep. 2021;16:2169-81.

34. Schneider SE, Scott AK, Gallagher KM, Miller EY, Ghosh S, Neu CP. Mechanical stress triggers premature senescence in cardiac fibroblasts. Adv Sci. 2025;12:e13314.

35. Angelini A, Ortiz-Urbina J, Trial J, et al. Sex-specific phenotypes in the aging mouse heart and consequences for chronic fibrosis. Am J Physiol Heart Circ Physiol. 2022;323:H285-300.

36. Ji H, Kwan AC, Chen MT, et al. Sex differences in myocardial and vascular aging. Circ Res. 2022;130:566-77.

37. Zheng X, Yao G, Yu H, et al. FBLN7 KO attenuates age-related cardiac fibrosis by promoting TGFBR3/ALK1/Smad1 signaling and inhibiting the profibrotic phenotypes of cardiac fibroblasts. Theranostics. 2025;15:8531-52.

38. Wagner JUG, Dimmeler S. Cellular cross-talks in the diseased and aging heart. J Mol Cell Cardiol. 2020;138:136-46.

39. Vagnozzi RJ, Molkentin JD. Resident macrophages keep mitochondria running in the heart. Cell Res. 2020;30:1057-8.

40. Nicolás-Ávila JA, Lechuga-Vieco AV, Esteban-Martínez L, et al. A network of macrophages supports mitochondrial homeostasis in the heart. Cell. 2020;183:94-109.e23.

41. Adao DMT, Ching C, Fish JE, Simmons CA, Billia F. Endothelial cell-cardiomyocyte cross-talk: understanding bidirectional paracrine signaling in cardiovascular homeostasis and disease. Clin Sci. 2024;138:1395-419.

42. Gao C, Xia Y, Li C, et al. KMV-mediated cardiomyocyte-to-endothelial cell signaling drives capillary rarefaction to promote heart failure following pressure overload. Theranostics. 2025;15:4970-88.

43. Tamiato A, Tombor LS, Fischer A, et al. Age-dependent RGS5 loss in pericytes induces cardiac dysfunction and fibrosis. Circ Res. 2024;134:1240-55.

44. Simon C, Greening DW, Bolumar D, Balaguer N, Salamonsen LA, Vilella F. Extracellular vesicles in human reproduction in health and disease. Endocr Rev. 2018;39:292-332.

45. Grigorian Shamagian L, Rogers RG, Luther K, et al. Rejuvenating effects of young extracellular vesicles in aged rats and in cellular models of human senescence. Sci Rep. 2023;13:12240.

46. Chen X, Luo Y, Zhu Q, et al. Small extracellular vesicles from young plasma reverse age-related functional declines by improving mitochondrial energy metabolism. Nat Aging. 2024;4:814-38.

47. Aijaz A, Bieerkehazhi S, Kang N, et al. Young extracellular vesicles restore burn-induced adipose tissue immunometabolic and mitochondrial function in older mice. Sci Rep. 2025;15:35328.

48. Sanz-Ros J, Huete-Acevedo J, Mas-Bargues C, et al. Small extracellular vesicles from young adipose-derived stem cells ameliorate age-related changes in the heart of old mice. Stem Cell Res Ther. 2025;16:138.

49. Saeedi Saravi SS, Bonetti NR, Vukolic A, et al. Long-term dietary n3 fatty acid prevents aging-related cardiac diastolic and vascular dysfunction. Vascul Pharmacol. 2023;150:107175.

50. Abdellatif M, Sedej S, Kroemer G. NAD+ metabolism in cardiac health, aging, and disease. Circulation. 2021;144:1795-817.

51. Santulli G, Kansakar U, Varzideh F, Mone P, Jankauskas SS, Lombardi A. Functional role of taurine in aging and cardiovascular health: an updated overview. Nutrients. 2023;15:4236.

52. Tang X, Li PH, Chen HZ. Cardiomyocyte senescence and cellular communications within myocardial microenvironments. Front Endocrinol 2020;11:280.

53. Morgado LAL, Rodrigues LMZ, Silva DCF, da Silva BD, Irigoyen MCC, Takano APC. NF-κB-specific suppression in cardiomyocytes unveils aging-associated responses in cardiac tissue. Biomedicines. 2025;13:224.

54. Yousef A, Fang L, Heidari M, Kranrod J, Seubert JM. The role of CYP-sEH derived lipid mediators in regulating mitochondrial biology and cellular senescence: implications for the aging heart. Front Pharmacol. 2024;15:1486717.

55. De Bartolo A, Rago V, Romeo N, et al. Unveiling selenoprotein T as a novel regulator of cardiomyocyte senescence: pivotal role of the CD36 receptor in AC16 human cardiomyocytes. GeroScience. 2026;48:1751-70.

56. de Boer M, Te Lintel Hekkert M, Chang J, et al. DNA repair in cardiomyocytes is critical for maintaining cardiac function in mice. Aging Cell. 2023;22:e13768.

57. Jiang R, Wang H, Zhang W, et al. DHT ameliorates cardiac aging in progeroid mice by XRCC4-mediated genome stabilization. Mech Ageing Dev. 2026;229:112141.

58. 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.

59. Maggiorani D, Santin Y, Formoso K, et al. Identification of Prominin-2 as a new player of cardiomyocyte senescence in the aging heart. Aging Cell. 2024;23:e14204.

60. Anderson R, Lagnado A, Maggiorani D, et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. 2019;38.

61. Qian W, Kumar N, Roginskaya V, et al. Chemoptogenetic damage to mitochondria causes rapid telomere dysfunction. Proc Natl Acad Sci U S A. 2019;116:18435-44.

62. Li B, Xiong W, Zuo W, et al. Proximal telomeric decompaction due to telomere shortening drives FOXC1-dependent myocardial senescence. Nucleic Acids Res. 2024;52:6269-84.

63. Calvani R, Joseph AM, Adhihetty PJ, et al. Mitochondrial pathways in sarcopenia of aging and disuse muscle atrophy. Biol Chem. 2013;394:393-414.

64. Pan G, Deshpande M, Pang H, et al. 4-Hydroxy-2-nonenal attenuates 8-oxoguanine DNA glycosylase 1 activity. J Cell Biochem. 2020;121:4887-97.

65. Rong Z, Tu P, Xu P, et al. The mitochondrial response to DNA damage. Front Cell Dev Biol. 2021;9:669379.

66. Manolis AS, Manolis AA, Manolis TA, et al. Mitochondrial dysfunction in cardiovascular disease: current status of translational research/clinical and therapeutic implications. Med Res Rev. 2021;41:275-313.

67. Elorza AA, Soffia JP. mtDNA heteroplasmy at the core of aging-associated heart failure. An integrative view of OXPHOS and mitochondrial life cycle in cardiac mitochondrial physiology. Front Cell Dev Biol. 2021;9:625020.

68. Sato M, Kadomatsu T, Morinaga J, et al. HINT1 suppression protects against age-related cardiac dysfunction by enhancing mitochondrial biogenesis. Mol Metab. 2025;93:102107.

69. Guo Y, You Y, Shang FF, et al. iNOS aggravates pressure overload-induced cardiac dysfunction via activation of the cytosolic-mtDNA-mediated cGAS-STING pathway. Theranostics. 2023;13:4229-46.

70. Gabillard-Lefort C, Thibault T, Lenaers G, Wiesner RJ, Mialet-Perez J, Baris OR. Heart of the matter: mitochondrial dynamics and genome alterations in cardiac aging. Mech Ageing Dev. 2025;224:112044.

71. Yan M, Li Y, Luo Q, et al. Mitochondrial damage and activation of the cytosolic DNA sensor cGAS-STING pathway lead to cardiac pyroptosis and hypertrophy in diabetic cardiomyopathy mice. Cell Death Discov. 2022;8:258.[DOI:10. 1038/s41420-022-01046-w].

72. Ichas F, Jouaville LS, Mazat JP. Mitochondria are excitable organelles capable of generating and conveying electrical and calcium signals. Cell. 1997;89:1145-53.

73. Glancy B, Hartnell LM, Malide D, et al. Mitochondrial reticulum for cellular energy distribution in muscle. Nature. 2015;523:617-20.

74. Glancy B, Hartnell LM, Combs CA, et al. Power grid protection of the muscle mitochondrial reticulum. Cell Rep. 2017;19:487-96.

75. El'darov ChM, Vays VB, Vangeli IM, Kolosova NG, Bakeeva LE. Morphometric examination of mitochondrial ultrastructure in aging cardiomyocytes. Biochemistry 2015;80:604-9.

76. Picca A, Lezza AM. Regulation of mitochondrial biogenesis through TFAM-mitochondrial DNA interactions: useful insights from aging and calorie restriction studies. Mitochondrion. 2015;25:67-75.

77. Zhang Y, Wang C, Zhou J, et al. Complex inhibition of autophagy by mitochondrial aldehyde dehydrogenase shortens lifespan and exacerbates cardiac aging. Biochim Biophys Acta Mol Basis Dis. 2017;1863:1919-32.

78. Shirakabe A, Ikeda Y, Sciarretta S, Zablocki DK, Sadoshima J. Aging and autophagy in the heart. Circ Res. 2016;118:1563-76.

79. Zhan S, Guo C, Yan H, Zheng G, Yan D. The multi-dimensional regulatory mechanism of Sirt6 in heart health: From cell death pathways to targeted therapy for cardiovascular diseases. Biochem Biophys Res Commun. 2025;782:152561.

80. Delbridge LMD, Mellor KM, Taylor DJ, Gottlieb RA. Myocardial stress and autophagy: mechanisms and potential therapies. Nat Rev Cardiol. 2017;14:412-25.

81. Hsu YJ, Hsu SC, Hsu CP, et al. Sirtuin 1 protects the aging heart from contractile dysfunction mediated through the inhibition of endoplasmic reticulum stress-mediated apoptosis in cardiac-specific Sirtuin 1 knockout mouse model. Int J Cardiol. 2017;228:543-52.

82. Kerrigan L, Edgar K, Russell-Hallinan A, et al. Integrin beta-like 1 is regulated by DNA methylation and increased in heart failure patients. ESC Heart Fail. 2025;12:150-65.

83. Si J, Chen L, Yu C, et al. ; China Kadoorie Biobank Collaborative Group. Healthy lifestyle, DNA methylation age acceleration, and incident risk of coronary heart disease. Clin Epigenetics. 2023;15:52.

84. Topriceanu CC, Dev E, Ahmad M, et al. Accelerated DNA methylation age plays a role in the impact of cardiovascular risk factors on the human heart. Clin Epigenetics. 2023;15:164.

85. Serio S, Pagiatakis C, Musolino E, et al. Cardiac aging is promoted by pseudohypoxia increasing p300-induced glycolysis. Circ Res. 2023;133:687-703.

86. Grzeczka A, Graczyk S, Gong X, Gröschel J, Spethmann S, Kordowitzki P. Aging hearts, fibrotic fears: The sirtuin connection. Biomed Pharmacother. 2025;193:118882.

87. Trembinski DJ, Bink DI, Theodorou K, et al. Aging-regulated anti-apoptotic long non-coding RNA Sarrah augments recovery from acute myocardial infarction. Nat Commun. 2020;11:2039.

88. Cabiati M, Sapio A, Salvadori C, et al. Evaluation of transcriptional levels of the natriuretic peptides, endothelin-1, adrenomedullin, their receptors and long non-coding RNAs in rat cardiac tissue as cardiovascular biomarkers of aging. Peptides. 2020;123:170173.

89. Jha S, Thasma Loganathbabu VK, Kumaran K, Krishnasamy G, Aruljothi KN. Long non-coding RNAs (lncRNAs) in heart failure: a comprehensive review. Noncoding RNA. 2023;10:3.

90. Lin R, Rahtu-Korpela L, Magga J, et al. miR-1468-3p promotes aging-related cardiac fibrosis. Mol Ther Nucleic Acids. 2020;20:589-605.

91. Pandey A, Kraus WE, Brubaker PH, Kitzman DW. Healthy aging and cardiovascular function: invasive hemodynamics during rest and exercise in 104 healthy volunteers. JACC Heart Fail. 2020;8:111-21.

92. Jefferis BJ, Parsons TJ, Sartini C, et al. Objectively measured physical activity, sedentary behaviour and all-cause mortality in older men: does volume of activity matter more than pattern of accumulation? Br J Sports Med 2019;53:1013-20.

93. Lin R, Rahtu-Korpela L, Magga J, et al. miR-1468-3p promotes aging-related cardiac fibrosis. Mol Ther Nucleic Acids. 2020;20:589-605.

94. Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail. 2010;3:588-95.

95. Howden EJ, Sarma S, Lawley JS, et al. Reversing the cardiac effects of sedentary aging in middle age-a randomized controlled trial: implications for heart failure prevention. Circulation. 2018;137:1549-60.

96. Beaumont AJ, Grace FM, Richards JC, Campbell AK, Sculthorpe NF. Aerobic training protects cardiac function during advancing age: a meta-analysis of four decades of controlled studies. Sports Med. 2019;49:199-219.

97. Fleg JL, Morrell CH, Bos AG, et al. Accelerated longitudinal decline of aerobic capacity in healthy older adults. Circulation. 2005;112:674-82.

98. Roh JD, Houstis N, Yu A, et al. Exercise training reverses cardiac aging phenotypes associated with heart failure with preserved ejection fraction in male mice. Aging Cell. 2020;19:e13159.

99. Green CL, Lamming DW, Fontana L. Molecular mechanisms of dietary restriction promoting health and longevity. Nat Rev Mol Cell Biol. 2022;23:56-73.

100. Radovic M, Gartzke LP, Wink SE, van der Kleij JA, Politiek FA, Krenning G. Targeting the electron transport system for enhanced longevity. Biomolecules. 2025;15:614.

101. Niemann B, Li L, Simm A, et al. Caloric restriction reduces sympathetic activity similar to beta-blockers but conveys additional mitochondrio-protective effects in aged myocardium. Sci Rep. 2021;11:1931.

102. Koutouroushis C, Sarkar O. Role of autophagy in cardiovascular disease and aging. Cureus. 2021;13:e20042.

103. Murillo-Cancho AF, Lozano-Paniagua D, Nievas-Soriano BJ. Dietary and pharmacological modulation of aging-related metabolic pathways: molecular insights, clinical evidence, and a translational model. Int J Mol Sci. 2025;26:9643.

104. Small S, Iglesies-Grau J, Gariepy C, Wilkinson M, Taub P, Kirkham A. Time-restricted eating: a novel dietary strategy for cardiac rehabilitation. Can J Cardiol. 2023;39:S384-94.

105. Gabel K, Cienfuegos S, Kalam F, Ezpeleta M, Varady KA. Time-restricted eating to improve cardiovascular health. Curr Atheroscler Rep. 2021;23:22.

106. Chaudhary S, Chaudhary MR, Jena MK, et al. Calorie restriction mimetics against aging and inflammation. Biogerontology. 2025;26:126.

107. Zhang Y, Mi SL, Hu N, et al. Mitochondrial aldehyde dehydrogenase 2 accentuates aging-induced cardiac remodeling and contractile dysfunction: role of AMPK, Sirt1, and mitochondrial function. Free Radic Biol Med. 2014;71:208-20.

108. Makino N, Maeda T. Calorie restriction delays cardiac senescence and improves cardiac function in obese diabetic rats. Mol Cell Biochem. 2021;476:221-9.

109. Weisel FJ, Mullett SJ, Elsner RA, et al. Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis. Nat Immunol. 2020;21:331-42.

110. Wang DD, Airhart SE, Zhou B, et al. Safety and tolerability of nicotinamide riboside in heart failure with reduced ejection fraction. JACC Basic Transl Sci. 2022;7:1183-96.

111. Ali MA, Gioscia-Ryan R, Yang D, Sutton NR, Tyrrell DJ. Cardiovascular aging: spotlight on mitochondria. Am J Physiol Heart Circ Physiol. 2024;326:H317-33.

112. Wang S, Long H, Hou L, et al. The mitophagy pathway and its implications in human diseases. Signal Transduct Target Ther. 2023;8:304.

113. Eisenberg T, Abdellatif M, Schroeder S, et al. Cardioprotection and lifespan extension by the natural polyamine spermidine. Nat Med. 2016;22:1428-38.

114. Hofer SJ, Simon AK, Bergmann M, Eisenberg T, Kroemer G, Madeo F. Mechanisms of spermidine-induced autophagy and geroprotection. Nat Aging. 2022;2:1112-29.

115. Hofer SJ, Daskalaki I, Bergmann M, et al. Spermidine is essential for fasting-mediated autophagy and longevity. Nat Cell Biol. 2024;26:1571-84.

116. D’Amico D, Andreux PA, Valdés P, Singh A, Rinsch C, Auwerx J. Impact of the natural compound urolithin a on health, disease, and aging. Trends Mol Med. 2021;27:687-99.

117. Andreux PA, Blanco-Bose W, Ryu D, et al. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019;1:595-603.

118. Huang JR, Zhang MH, Chen YJ, et al. Urolithin A ameliorates obesity-induced metabolic cardiomyopathy in mice via mitophagy activation. Acta Pharmacol Sin. 2023;44:321-31.

119. Liu S, D’Amico D, Shankland E, et al. Effect of urolithin a supplementation on muscle endurance and mitochondrial health in older adults: a randomized clinical trial. JAMA Netw Open. 2022;5:e2144279.

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