REFERENCES

1. Di Cesare M, Perel P, Taylor S, et al. The heart of the world. Glob Heart. 2024;19:11.

2. Gómez LA. [Cardiovascular diseases: a public health problem and a global challenge]. Biomedica. 2011;31:469-73.

3. Yazdanyar A, Newman AB. The burden of cardiovascular disease in the elderly: morbidity, mortality, and costs. Clin Geriatr Med. 2009;25:563-77, vii.

4. Niklasson A, Maher J, Patil R, et al. Living with heart failure: patient experiences and implications for physical activity and daily living. ESC Heart Fail. 2022;9:1206-15.

5. Mulugeta H, Sinclair PM, Wilson A. The experience of people living with heart failure in Ethiopia: a qualitative descriptive study. PLoS One. 2024;19:e0310600.

6. Kreatsoulas C, Anand SS. The impact of social determinants on cardiovascular disease. Can J Cardiol. 2010;26 Suppl C:8C-13C.

7. Lopez AD, Mathers CD, Ezzati M, Jamison DT, Murray CJ. Global and regional burden of disease and risk factors, 2001: systematic analysis of population health data. Lancet. 2006;367:1747-57.

8. Alizadeh G, Gholipour K, Azami-Aghdash S, et al. Social, economic, technological, and environmental factors affecting cardiovascular diseases: a systematic review and thematic analysis. Int J Prev Med. 2022;13:78.

9. Ziaeian B, Fonarow GC. The prevention of hospital readmissions in heart failure. Prog Cardiovasc Dis. 2016;58:379-85.

10. Cohn JN, Ferrari R, Sharpe N. Cardiac remodeling-concepts and clinical implications: a consensus paper from an international forum on cardiac remodeling. Behalf of an International Forum on Cardiac Remodeling. J Am Coll Cardiol. 2000;35:569-82.

11. Hill JA, Olson EN. Cardiac plasticity. N Engl J Med. 2008;358:1370-80.

12. 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.

13. McDonagh TA, Metra M, Adamo M, et al. 2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur Heart J. 2021;42:3599-726.

14. Del Campo A, Perez G, Castro PF, Parra V, Verdejo HE. Mitochondrial function, dynamics and quality control in the pathophysiology of HFpEF. Biochim Biophys Acta Mol Basis Dis. 2021;1867:166208.

15. Paraskevaidis I, Kourek C, Farmakis D, Tsougos E. Mitochondrial dysfunction in cardiac disease: the fort fell. Biomolecules. 2024;14:1534.

16. Schwartz B, Gjini P, Gopal DM, Fetterman JL. Inefficient batteries in heart failure: metabolic bottlenecks disrupting the mitochondrial ecosystem. JACC Basic Transl Sci. 2022;7:1161-79.

17. Calle X, Garrido-Moreno V, Lopez-Gallardo E, et al. Mitochondrial E3 ubiquitin ligase 1 (MUL1) as a novel therapeutic target for diseases associated with mitochondrial dysfunction. IUBMB Life. 2022;74:850-65.

18. Liu H, Mao H, Ouyang X, Lu R, Li L. Intercellular mitochondrial transfer: the novel therapeutic mechanism for diseases. Traffic. 2024;25:e12951.

19. Ávila PM, Morales HF, Quirós-Meza G, Salazar-Nassar J, Castillo-Rivas J, Castillo-Rivas J. Prevalencia y factores de riesgo de enfermedad ateroesclerótica sistémica. Acta Méd Costarricense. 2014;56:6-11.

20. Frąk W, Wojtasińska A, Lisińska W, Młynarska E, Franczyk B, Rysz J. Pathophysiology of cardiovascular diseases: new insights into molecular mechanisms of atherosclerosis, arterial hypertension, and coronary artery disease. Biomedicines. 2022;10:1938.

21. Papazoglou AS, Kyriakoulis KG, Barmpagiannos K, et al. Atherosclerotic risk factor prevalence in adults with congenital heart disease: a meta-analysis. JACC Adv. 2024;3:101359.

22. Kim S, Khoriaty R, Li L, et al. ER-to-golgi transport and SEC23-dependent COPII vesicles regulate T cell alloimmunity. J Clin Invest. 2021;131:136574.

23. Lodhi IJ, Semenkovich CF. Peroxisomes: a nexus for lipid metabolism and cellular signaling. Cell Metab. 2014;19:380-92.

24. Nikolich-Žugich J. The twilight of immunity: emerging concepts in aging of the immune system. Nat Immunol. 2018;19:10-9.

25. Paillusson S, Stoica R, Gomez-Suaga P, et al. There's something wrong with my MAM; the ER-mitochondria axis and neurodegenerative diseases. Trends Neurosci. 2016;39:146-57.

26. Quirós PM, Mottis A, Auwerx J. Mitonuclear communication in homeostasis and stress. Nat Rev Mol Cell Biol. 2016;17:213-26.

27. Franceschi C, Garagnani P, Parini P, Giuliani C, Santoro A. Inflammaging: a new immune-metabolic viewpoint for age-related diseases. Nat Rev Endocrinol. 2018;14:576-90.

28. Chung JY, Ain QU, Song Y, Yong SB, Kim YH. Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance. Genome Res. 2019;29:1442-52.

29. Mone P, Agyapong ED, Morciano G, et al. Dysfunctional mitochondria elicit bioenergetic decline in the aged heart. J Cardiovasc Aging. 2024;4:13.

30. Murphy E, Ardehali H, Balaban RS, et al. Mitochondrial function, biology, and role in disease: a scientific statement from the american heart association. Circ Res. 2016;118:1960-91.

31. Nguyen BY, Ruiz-Velasco A, Bui T, Collins L, Wang X, Liu W. Mitochondrial function in the heart: the insight into mechanisms and therapeutic potentials. Br J Pharmacol. 2019;176:4302-18.

32. Martín-Fernández B, Gredilla R. Mitochondria and oxidative stress in heart aging. Age. 2016;38:225-38.

33. Muthu S, Tran Z, Thilagavathi J, et al. Aging triggers mitochondrial, endoplasmic reticulum, and metabolic stress responses in the heart. J Cardiovasc Aging. 2025;5:4.

34. Rosca MG, Hoppel CL. Mitochondria in heart failure. Cardiovasc Res. 2010;88:40-50.

35. Liu SZ, Marcinek DJ. Skeletal muscle bioenergetics in aging and heart failure. Heart Fail Rev. 2017;22:167-78.

36. Lesnefsky EJ, Chen Q, Hoppel CL. Mitochondrial metabolism in aging heart. Circ Res. 2016;118:1593-611.

37. Tatarková Z, Kuka S, Račay P, et al. Effects of aging on activities of mitochondrial electron transport chain complexes and oxidative damage in rat heart. Physiol Res. 2011;60:281-9.

38. Tocchi A, Quarles EK, Basisty N, Gitari L, Rabinovitch PS. Mitochondrial dysfunction in cardiac aging. Biochim Biophys Acta. 2015;1847:1424-33.

39. Sithara T, Drosatos K. Metabolic complications in cardiac aging. Front Physiol. 2021;12:669497.

40. Chen Y, Liu Y, Dorn GW 2nd. Mitochondrial fusion is essential for organelle function and cardiac homeostasis. Circ Res. 2011;109:1327-31.

41. Scheffer DDL, Garcia AA, Lee L, Mochly-Rosen D, Ferreira JCB. Mitochondrial fusion, fission, and mitophagy in cardiac diseases: challenges and therapeutic opportunities. Antioxid Redox Signal. 2022;36:844-63.

42. Zerihun M, Sukumaran S, Qvit N. The Drp1-mediated mitochondrial fission protein interactome as an emerging core player in mitochondrial dynamics and cardiovascular disease therapy. Int J Mol Sci. 2023;24:5785.

43. Łysek-Gładysińska M, Wieczorek A, Jóźwik A, et al. Aging-related changes in the ultrastructure of hepatocytes and cardiomyocytes of elderly mice are enhanced in ApoE-deficient animals. Cells. 2021;10:502.

44. Fernández-Ortiz M, Sayed RKA, Fernández-Martínez J, et al. Melatonin/Nrf2/NLRP3 connection in mouse heart mitochondria during aging. Antioxidants. 2020;9:1187.

45. Vue Z, Neikirk K, Vang L, et al. Three-dimensional mitochondria reconstructions of murine cardiac muscle changes in size across aging. Am J Physiol Heart Circ Physiol. 2023;325:H965-82.

46. Chaanine AH, Jeong D, Liang L, et al. JNK modulates FOXO3a for the expression of the mitochondrial death and mitophagy marker BNIP3 in pathological hypertrophy and in heart failure. Cell Death Dis. 2012;3:265.

47. Liu T, Chen L, Kim E, Tran D, Phinney BS, Knowlton AA. Mitochondrial proteome remodeling in ischemic heart failure. Life Sci. 2014;101:27-36.

48. Wai T, García-Prieto J, Baker MJ, et al. Imbalanced OPA1 processing and mitochondrial fragmentation cause heart failure in mice. Science. 2015;350:aad0116.

49. Ikeda Y, Shirakabe A, Maejima Y, et al. Endogenous Drp1 mediates mitochondrial autophagy and protects the heart against energy stress. Circ Res. 2015;116:264-78.

50. Song M, Franco A, Fleischer JA, Zhang L, Dorn GW 2nd. Abrogating mitochondrial dynamics in mouse hearts accelerates mitochondrial senescence. Cell Metab. 2017;26:872-83.e5.

51. Zhao L, Zou X, Feng Z, et al. Evidence for association of mitochondrial metabolism alteration with lipid accumulation in aging rats. Exp Gerontol. 2014;56:3-12.

52. Wang Y, Li Y, He C, Gou B, Song M. Mitochondrial regulation of cardiac aging. Biochim Biophys Acta Mol Basis Dis. 2019;1865:1853-64.

53. Gao B, Yu W, Lv P, Liang X, Sun S, Zhang Y. Parkin overexpression alleviates cardiac aging through facilitating K63-polyubiquitination of TBK1 to facilitate mitophagy. Biochim Biophys Acta Mol Basis Dis. 2021;1867:165997.

54. Hafner AV, Dai J, Gomes AP, et al. Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging. 2010;2:914-23.

55. Paradies G, Paradies V, Ruggiero FM, Petrosillo G. Changes in the mitochondrial permeability transition pore in aging and age-associated diseases. Mech Ageing Dev. 2013;134:1-9.

56. Kwong JQ, Molkentin JD. Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metab. 2015;21:206-14.

57. Strutynska NA, Kotsiuruba AV, Budko AY, Mys LA, Sagach VF. Mitochondrial dysfunction in the aging heart is accompanied by constitutive no-synthases uncoupling on the background of oxidative and nitrosative stress. Fiziol Zh (1994). 2016;62:3-11.

58. Phaneuf S, Leeuwenburgh C. Cytochrome c release from mitochondria in the aging heart: a possible mechanism for apoptosis with age. Am J Physiol Regul Integr Comp Physiol. 2002;282:R423-30.

59. Hofer T, Servais S, Seo AY, et al. Bioenergetics and permeability transition pore opening in heart subsarcolemmal and interfibrillar mitochondria: effects of aging and lifelong calorie restriction. Mech Ageing Dev. 2009;130:297-307.

60. Chen Q, Thompson J, Hu Y, et al. High-dose metformin treatment to inhibit complex I during early reperfusion protects the aged mouse heart via decreased mitochondrial permeability transition pore opening. J Pharmacol Exp Ther. 2024;392:100529.

61. Zhang J, Zhao Y, Gong N. Endoplasmic reticulum stress signaling modulates ischemia/reperfusion injury in the aged heart by regulating mitochondrial maintenance. Mol Med. 2024;30:107.

62. Lam A, Karekar P, Shah K, et al. Drosophila voltage-gated calcium channel α1-subunits regulate cardiac function in the aging heart. Sci Rep. 2018;8:6910.

63. Bers DM. Cardiac excitation-contraction coupling. Nature. 2002;415:198-205.

64. Eisner DA, Caldwell JL, Kistamás K, Trafford AW. Calcium and excitation-contraction coupling in the heart. Circ Res. 2017;121:181-95.

65. Mehdizadeh M, Aguilar M, Thorin E, Ferbeyre G, Nattel S. The role of cellular senescence in cardiac disease: basic biology and clinical relevance. Nat Rev Cardiol. 2022;19:250-64.

66. Györke S, Carnes C. Dysregulated sarcoplasmic reticulum calcium release: potential pharmacological target in cardiac disease. Pharmacol Ther. 2008;119:340-54.

67. Brette F, Sallé L, Orchard CH. Differential modulation of L-type Ca2+ current by SR Ca2+ release at the T-tubules and surface membrane of rat ventricular myocytes. Circ Res. 2004;95:e1-7.

68. Guo A, Zhang C, Wei S, Chen B, Song LS. Emerging mechanisms of T-tubule remodelling in heart failure. Cardiovasc Res. 2013;98:204-15.

69. Gil-Hernández A, Silva-Palacios A. Relevance of endoplasmic reticulum and mitochondria interactions in age-associated diseases. Ageing Res Rev. 2020;64:101193.

70. Wisneski JA, Stanley WC, Neese RA, Gertz EW. Effects of acute hyperglycemia on myocardial glycolytic activity in humans. J Clin Invest. 1990;85:1648-56.

71. Koss KL, Kranias EG. Phospholamban: a prominent regulator of myocardial contractility. Circ Res. 1996;79:1059-63.

72. Hetz C, Zhang K, Kaufman RJ. Mechanisms, regulation and functions of the unfolded protein response. Nat Rev Mol Cell Biol. 2020;21:421-38.

73. Bravo R, Parra V, Gatica D, et al. Endoplasmic reticulum and the unfolded protein response: dynamics and metabolic integration. Int Rev Cell Mol Biol. 2013;301:215-90.

74. Hotamisligil GS. Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. Cell. 2010;140:900-17.

75. Wang X, Xu L, Gillette TG, Jiang X, Wang ZV. The unfolded protein response in ischemic heart disease. J Mol Cell Cardiol. 2018;117:19-25.

76. Liberale L, Badimon L, Montecucco F, Lüscher TF, Libby P, Camici GG. Inflammation, aging, and cardiovascular disease: JACC review topic of the week. J Am Coll Cardiol. 2022;79:837-47.

77. Weber C, Habenicht AJR, von Hundelshausen P. Novel mechanisms and therapeutic targets in atherosclerosis: inflammation and beyond. Eur Heart J. 2023;44:2672-81.

78. Franceschi C, Garagnani P, Vitale G, Capri M, Salvioli S. Inflammaging and 'garb-aging'. Trends Endocrinol Metab. 2017;28:199-212.

79. Ferrucci L, Corsi A, Lauretani F, et al. The origins of age-related proinflammatory state. Blood. 2005;105:2294-9.

80. Youm YH, Grant RW, McCabe LR, et al. Canonical Nlrp3 inflammasome links systemic low-grade inflammation to functional decline in aging. Cell Metab. 2013;18:519-32.

81. Luo W, Zou X, Wang Y, et al. Critical role of the cGAS-STING pathway in doxorubicin-induced cardiotoxicity. Circ Res. 2023;132:e223-42.

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

83. Gilsbach R, Schwaderer M, Preissl S, et al. Distinct epigenetic programs regulate cardiac myocyte development and disease in the human heart in vivo. Nat Commun. 2018;9:391.

84. Bannister AJ, Kouzarides T. Regulation of chromatin by histone modifications. Cell Res. 2011;21:381-95.

85. Lans H, Marteijn JA, Vermeulen W. ATP-dependent chromatin remodeling in the DNA-damage response. Epigenetics Chromatin. 2012;5:4.

86. Emerson FJ, Lee SS. Chromatin: the old and young of it. Front Mol Biosci. 2023;10:1270285.

87. Liu B, Yip RKh, Zhou Z. Chromatin remodeling, DNA damage repair and aging. Curr Genomics. 2012;13:533-47.

88. Muñoz-Lorente MA, Cano-Martin AC, Blasco MA. Mice with hyper-long telomeres show less metabolic aging and longer lifespans. Nat Commun. 2019;10:4723.

89. Paneni F, Diaz Cañestro C, Libby P, Lüscher TF, Camici GG. The aging cardiovascular system: understanding it at the cellular and clinical levels. J Am Coll Cardiol. 2017;69:1952-67.

90. McKinsey TA, Vondriska TM, Wang Y. Epigenomic regulation of heart failure: integrating histone marks, long noncoding RNAs, and chromatin architecture. F1000Res. 2018;7:1713.

91. Han P, Hang CT, Yang J, Chang CP. Chromatin remodeling in cardiovascular development and physiology. Circ Res. 2011;108:378-96.

92. Mahmoud SA, Poizat C. Epigenetics and chromatin remodeling in adult cardiomyopathy. J Pathol. 2013;231:147-57.

93. Mathiyalagan P, Keating ST, Du XJ, El-Osta A. Chromatin modifications remodel cardiac gene expression. Cardiovasc Res. 2014;103:7-16.

94. Alcendor RR, Gao S, Zhai P, et al. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res. 2007;100:1512-21.

95. Matsushima S, Sadoshima J. The role of sirtuins in cardiac disease. Am J Physiol Heart Circ Physiol. 2015;309:H1375-89.

96. Ministrini S, Puspitasari YM, Beer G, Liberale L, Montecucco F, Camici GG. Sirtuin 1 in endothelial dysfunction and cardiovascular aging. Front Physiol. 2021;12:733696.

97. Rodriguez F, Seta F. Editorial: the role of sirtuin-1 in cardiovascular and renal pathophysiology. Front Physiol. 2021;12:770386.

98. Sciarretta S, Maejima Y, Zablocki D, Sadoshima J. The role of autophagy in the heart. Annu Rev Physiol. 2018;80:1-26.

99. Liu Y, Shoji-Kawata S, Sumpter RM Jr, et al. Autosis is a Na+,K+-ATPase-regulated form of cell death triggered by autophagy-inducing peptides, starvation, and hypoxia-ischemia. Proc Natl Acad Sci USA. 2013;110:20364-71.

100. Li F, Lang F, Zhang H, Xu L, Wang Y, Hao E. Role of TFEB mediated autophagy, oxidative stress, inflammation, and cell death in endotoxin induced myocardial toxicity of young and aged mice. Oxid Med Cell Longev. 2016;2016:5380319.

101. Okura Y, Brink M, Itabe H, Scheidegger KJ, Kalangos A, Delafontaine P. Oxidized low-density lipoprotein is associated with apoptosis of vascular smooth muscle cells in human atherosclerotic plaques. Circulation. 2000;102:2680-6.

102. Zhang AY, Yi F, Zhang G, Gulbins E, Li PL. Lipid raft clustering and redox signaling platform formation in coronary arterial endothelial cells. Hypertension. 2006;47:74-80.

103. Tanaka Y, Guhde G, Suter A, et al. Accumulation of autophagic vacuoles and cardiomyopathy in LAMP-2-deficient mice. Nature. 2000;406:902-6.

104. Wang J, Cheng X, Xiang MX, et al. IgE stimulates human and mouse arterial cell apoptosis and cytokine expression and promotes atherogenesis in Apoe-/- mice. J Clin Invest. 2011;121:3564-77.

105. Terman A, Kurz T, Gustafsson B, Brunk UT. The involvement of lysosomes in myocardial aging and disease. Curr Cardiol Rev. 2008;4:107-15.

106. Bhat OM, Li PL. Lysosome function in cardiovascular diseases. Cell Physiol Biochem. 2021;55:277-300.

107. Wilfling F, Haas JT, Walther TC, Farese RV Jr. Lipid droplet biogenesis. Curr Opin Cell Biol. 2014;29:39-45.

108. Dalhaimer P. Lipid droplets in disease. Cells. 2019;8:974.

109. Bresgen N, Kovacs M, Lahnsteiner A, Felder TK, Rinnerthaler M. The Janus-faced role of lipid droplets in aging: insights from the cellular perspective. Biomolecules. 2023;13:912.

110. Perrotta I. Interaction between lipid droplets and endoplasmic reticulum in human atherosclerotic plaques. Ultrastruct Pathol. 2017;41:1-9.

111. Moldavski O, Amen T, Levin-Zaidman S, et al. Lipid droplets are essential for efficient clearance of cytosolic inclusion bodies. Dev Cell. 2015;33:603-10.

112. Hammoudeh N, Soukkarieh C, Murphy DJ, Hanano A. Involvement of hepatic lipid droplets and their associated proteins in the detoxification of aflatoxin B1 in aflatoxin-resistance BALB/C mouse. Toxicol Rep. 2020;7:795-804.

113. Bosch M, Sánchez-Álvarez M, Fajardo A, et al. Mammalian lipid droplets are innate immune hubs integrating cell metabolism and host defense. Science. 2020;370:eaay8085.

114. Choudhary V, Golani G, Joshi AS, et al. Architecture of lipid droplets in endoplasmic reticulum is determined by phospholipid intrinsic curvature. Curr Biol. 2018;28:915-26.e9.

115. Lopaschuk GD, Ussher JR, Folmes CD, Jaswal JS, Stanley WC. Myocardial fatty acid metabolism in health and disease. Physiol Rev. 2010;90:207-58.

116. Osumi T, Kuramoto K. Heart lipid droplets and lipid droplet-binding proteins: biochemistry, physiology, and pathology. Exp Cell Res. 2016;340:198-204.

117. Goldberg IJ, Reue K, Abumrad NA, et al. Deciphering the role of lipid droplets in cardiovascular disease: a report from the 2017 national heart, lung, and blood institute workshop. Circulation. 2018;138:305-15.

118. Chen Y, Yang L, Wang K, et al. Relationship between fatty acid intake and aging: a Mendelian randomization study. Aging. 2024;16:5711-39.

119. Valencak TG, Ruf T. Feeding into old age: long-term effects of dietary fatty acid supplementation on tissue composition and life span in mice. J Comp Physiol B. 2011;181:289-98.

120. Papsdorf K, Miklas JW, Hosseini A, et al. Lipid droplets and peroxisomes are co-regulated to drive lifespan extension in response to mono-unsaturated fatty acids. Nat Cell Biol. 2023;25:672-84.

121. Guo D, Zhang M, Qi B, et al. Lipid overload-induced RTN3 activation leads to cardiac dysfunction by promoting lipid droplet biogenesis. Cell Death Differ. 2024;31:292-308.

122. Jebessa ZH, Shanmukha KD, Dewenter M, et al. The lipid droplet-associated protein ABHD5 protects the heart through proteolysis of HDAC4. Nat Metab. 2019;1:1157-67.

123. Han L, Huang D, Wu S, et al. Lipid droplet-associated lncRNA LIPTER preserves cardiac lipid metabolism. Nat Cell Biol. 2023;25:1033-46.

124. Kuramoto K, Sakai F, Yoshinori N, et al. Deficiency of a lipid droplet protein, perilipin 5, suppresses myocardial lipid accumulation, thereby preventing type 1 diabetes-induced heart malfunction. Mol Cell Biol. 2014;34:2721-31.

125. Poston CN, Krishnan SC, Bazemore-Walker CR. In-depth proteomic analysis of mammalian mitochondria-associated membranes (MAM). J Proteomics. 2013;79:219-30.

126. Li J, Zhang D, Brundel BJJM, Wiersma M. Imbalance of ER and mitochondria interactions: prelude to cardiac ageing and disease? Cells. 2019;8:1617.

127. Lopez-Crisosto C, Pennanen C, Vasquez-Trincado C, et al. Sarcoplasmic reticulum-mitochondria communication in cardiovascular pathophysiology. Nat Rev Cardiol. 2017;14:342-60.

128. Carpio MA, Means RE, Brill AL, Sainz A, Ehrlich BE, Katz SG. BOK controls apoptosis by Ca2+ transfer through ER-mitochondrial contact sites. Cell Rep. 2021;34:108827.

129. Rasola A, Bernardi P. Mitochondrial permeability transition in Ca2+-dependent apoptosis and necrosis. Cell Calcium. 2011;50:222-33.

130. Hu Y, Chen H, Zhang L, et al. The AMPK-MFN2 axis regulates MAM dynamics and autophagy induced by energy stresses. Autophagy. 2021;17:1142-56.

131. Shoshan-Barmatz V, De S, Meir A. The mitochondrial voltage-dependent anion channel 1, Ca2+ transport, apoptosis, and their regulation. Front Oncol. 2017;7:60.

132. Loncke J, de Ridder I, Kale J, et al. CISD2 counteracts the inhibition of ER-mitochondrial calcium transfer by anti-apoptotic BCL-2. Biochim Biophys Acta Mol Cell Res. 2025;1872:119857.

133. Wang CH, Chen YF, Wu CY, et al. Cisd2 modulates the differentiation and functioning of adipocytes by regulating intracellular Ca2+ homeostasis. Hum Mol Genet. 2014;23:4770-85.

134. Yeh CH, Chou YJ, Kao CH, Tsai TF. Mitochondria and calcium homeostasis: Cisd2 as a big player in cardiac ageing. Int J Mol Sci. 2020;21:9238.

135. Chen YF, Kao CH, Chen YT, et al. Cisd2 deficiency drives premature aging and causes mitochondria-mediated defects in mice. Genes Dev. 2009;23:1183-94.

136. Janikiewicz J, Szymański J, Malinska D, et al. Mitochondria-associated membranes in aging and senescence: structure, function, and dynamics. Cell Death Dis. 2018;9:332.

137. Wang C, Dai X, Wu S, et al. FUNDC1-dependent mitochondria-associated endoplasmic reticulum membranes are involved in angiogenesis and neoangiogenesis. Nat Commun. 2024;15:4572.

138. Wu S, Lu Q, Wang Q, et al. Binding of FUN14 domain containing 1 with inositol 1,4,5-trisphosphate receptor in mitochondria-associated endoplasmic reticulum membranes maintains mitochondrial dynamics and function in hearts in vivo. Circulation. 2017;136:2248-66.

139. Lagendijk AK, Szabó A, Merks RM, Bakkers J. Hyaluronan: a critical regulator of endothelial-to-mesenchymal transition during cardiac valve formation. Trends Cardiovasc Med. 2013;23:135-42.

140. Morgado-Cáceres P, Liabeuf G, Calle X, et al. The aging of ER-mitochondria communication: a journey from undifferentiated to aged cells. Front Cell Dev Biol. 2022;10:946678.

141. Jentsch TJ, Stein V, Weinreich F, Zdebik AA. Molecular structure and physiological function of chloride channels. Physiol Rev. 2002;82:503-68.

142. Li D, Li Y, Ding H, Wang Y, Xie Y, Zhang X. Cellular senescence in cardiovascular diseases: from pathogenesis to therapeutic challenges. J Cardiovasc Dev Dis. 2023;10:439.

143. Setterberg IE, Le C, Frisk M, Perdreau-Dahl H, Li J, Louch WE. The physiology and pathophysiology of T-tubules in the heart. Front Physiol. 2021;12:790227.

144. Kostin S, Scholz D, Shimada T, et al. The internal and external protein scaffold of the T-tubular system in cardiomyocytes. Cell Tissue Res. 1998;294:449-60.

145. Louch WE, Mørk HK, Sexton J, et al. T-tubule disorganization and reduced synchrony of Ca2+ release in murine cardiomyocytes following myocardial infarction. J Physiol. 2006;574:519-33.

146. Retzius G. Zur Kenntnis der quergestreiften Muskelfaser. Biol Untersuch. 1881:1-11. Available from: https://www.zobodat.at/pdf/Biolog-Untersuchungen_1_0001-0026.pdf [Last accessed on 10 Oct 2025].

147. Heinzel FR, Bito V, Biesmans L, et al. Remodeling of T-tubules and reduced synchrony of Ca2+ release in myocytes from chronically ischemic myocardium. Circ Res. 2008;102:338-46.

148. Louch WE, Bito V, Heinzel FR, et al. Reduced synchrony of Ca2+ release with loss of T-tubules-a comparison to Ca2+ release in human failing cardiomyocytes. Cardiovasc Res. 2004;62:63-73.

149. Zhang HB, Li RC, Xu M, et al. Ultrastructural uncoupling between T-tubules and sarcoplasmic reticulum in human heart failure. Cardiovasc Res. 2013;98:269-76.

150. Zorn-Pauly K, Schaffer P, Pelzmann B, et al. Oxidized LDL induces ventricular myocyte damage and abnormal electrical activity-role of lipid hydroperoxides. Cardiovasc Res. 2005;66:74-83.

151. Bertic M, Worme M, Foroutan F, et al. Predictors of survival and favorable neurologic outcome in patients treated with eCPR: a systematic review and meta-analysis. J Cardiovasc Transl Res. 2022;15:279-90.

152. Kho C, Lee A, Hajjar RJ. Altered sarcoplasmic reticulum calcium cycling-targets for heart failure therapy. Nat Rev Cardiol. 2012;9:717-33.

153. Rog-Zielinska EA, Scardigli M, Peyronnet R, et al. Beat-by-beat cardiomyocyte T-tubule deformation drives tubular content exchange. Circ Res. 2021;128:203-15.

154. Anderson R, Prolla T. PGC-1alpha in aging and anti-aging interventions. Biochim Biophys Acta. 2009;1790:1059-66.

155. Gao F, Liang T, Lu YW, et al. Reduced mitochondrial protein translation promotes cardiomyocyte proliferation and heart regeneration. Circulation. 2023;148:1887-906.

156. Gao F, Liang T, Lu YW, et al. A defect in mitochondrial protein translation influences mitonuclear communication in the heart. Nat Commun. 2023;14:1595.

157. Anderson R, Lagnado A, Maggiorani D, et al. Length-independent telomere damage drives post-mitotic cardiomyocyte senescence. EMBO J. 2019;38:e100492.

158. Lai L, Leone TC, Zechner C, et al. Transcriptional coactivators PGC-1alpha and PGC-lbeta control overlapping programs required for perinatal maturation of the heart. Genes Dev. 2008;22:1948-61.

159. Sahin E, Colla S, Liesa M, et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature. 2011;470:359-65.

160. Dai DF, Rabinovitch PS, Ungvari Z. Mitochondria and cardiovascular aging. Circ Res. 2012;110:1109-24.

161. Gomes AP, Price NL, Ling AJ, et al. Declining NAD+ induces a pseudohypoxic state disrupting nuclear-mitochondrial communication during aging. Cell. 2013;155:1624-38.

162. Zhu D, Li X, Tian Y. Mitochondrial-to-nuclear communication in aging: an epigenetic perspective. Trends Biochem Sci. 2022;47:645-59.

163. Yu W, Sun S, Xu H, Li C, Ren J, Zhang Y. TBC1D15/RAB7-regulated mitochondria-lysosome interaction confers cardioprotection against acute myocardial infarction-induced cardiac injury. Theranostics. 2020;10:11244-63.

164. Sun S, Yu W, Xu H, et al. TBC1D15-Drp1 interaction-mediated mitochondrial homeostasis confers cardioprotection against myocardial ischemia/reperfusion injury. Metabolism. 2022;134:155239.

165. Liao PC, Yang EJ, Borgman T, et al. Touch and Go: membrane contact sites between lipid droplets and other organelles. Front Cell Dev Biol. 2022;10:852021.

166. Kim J, Bai H. Peroxisomal stress response and inter-organelle communication in cellular homeostasis and aging. Antioxidants. 2022;11:192.

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

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

169. Chen F, Jimenez RJ, Sharma K, et al. Broad distribution of hepatocyte proliferation in liver homeostasis and regeneration. Cell Stem Cell. 2020;26:27-33.e4.

170. Burté F, Carelli V, Chinnery PF, Yu-Wai-Man P. Disturbed mitochondrial dynamics and neurodegenerative disorders. Nat Rev Neurol. 2015;11:11-24.

171. Plotegher N, Duchen MR. Mitochondrial dysfunction and neurodegeneration in lysosomal storage disorders. Trends Mol Med. 2017;23:116-34.

172. Wong YC, Kim S, Peng W, Krainc D. Regulation and function of mitochondria-lysosome membrane contact sites in cellular homeostasis. Trends Cell Biol. 2019;29:500-13.

173. Deus CM, Yambire KF, Oliveira PJ, Raimundo N. Mitochondria-lysosome crosstalk: from physiology to neurodegeneration. Trends Mol Med. 2020;26:71-88.

174. Ballabio A, Bonifacino JS. Lysosomes as dynamic regulators of cell and organismal homeostasis. Nat Rev Mol Cell Biol. 2020;21:101-18.

175. Cartes-Saavedra B, Ghosh A, Hajnóczky G. The roles of mitochondria in global and local intracellular calcium signalling. Nat Rev Mol Cell Biol. 2025;26:456-75.

176. Sugiura A, McLelland GL, Fon EA, McBride HM. A new pathway for mitochondrial quality control: mitochondrial-derived vesicles. EMBO J. 2014;33:2142-56.

177. Hamacher-Brady A, Choe SC, Krijnse-Locker J, Brady NR. Intramitochondrial recruitment of endolysosomes mediates Smac degradation and constitutes a novel intrinsic apoptosis antagonizing function of XIAP E3 ligase. Cell Death Differ. 2014;21:1862-76.

178. Wong YC, Holzbaur EL. Optineurin is an autophagy receptor for damaged mitochondria in parkin-mediated mitophagy that is disrupted by an ALS-linked mutation. Proc Natl Acad Sci USA. 2014;111:E4439-48.

179. Lazarou M, Sliter DA, Kane LA, et al. The ubiquitin kinase PINK1 recruits autophagy receptors to induce mitophagy. Nature. 2015;524:309-14.

180. McLelland GL, Soubannier V, Chen CX, McBride HM, Fon EA. Parkin and PINK1 function in a vesicular trafficking pathway regulating mitochondrial quality control. EMBO J. 2014;33:282-95.

181. Wong YC, Ysselstein D, Krainc D. Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis. Nature. 2018;554:382-6.

182. Zhang XM, Walsh B, Mitchell CA, Rowe T. TBC domain family, member 15 is a novel mammalian Rab GTPase-activating protein with substrate preference for Rab7. Biochem Biophys Res Commun. 2005;335:154-61.

183. Peralta ER, Martin BC, Edinger AL. Differential effects of TBC1D15 and mammalian Vps39 on Rab7 activation state, lysosomal morphology, and growth factor dependence. J Biol Chem. 2010;285:16814-21.

184. Onoue K, Jofuku A, Ban-Ishihara R, et al. Fis1 acts as a mitochondrial recruitment factor for TBC1D15 that is involved in regulation of mitochondrial morphology. J Cell Sci. 2013;126:176-85.

185. Meggouh F, Bienfait HM, Weterman MA, de Visser M, Baas F. Charcot-marie-tooth disease due to a de novo mutation of the RAB7 gene. Neurology. 2006;67:1476-8.

186. Itoh K, Adachi Y, Yamada T, et al. A brain-enriched Drp1 isoform associates with lysosomes, late endosomes, and the plasma membrane. J Biol Chem. 2018;293:11809-22.

187. Rossor AM, Tomaselli PJ, Reilly MM. Recent advances in the genetic neuropathies. Curr Opin Neurol. 2016;29:537-48.

188. Burbulla LF, Song P, Mazzulli JR, et al. Dopamine oxidation mediates mitochondrial and lysosomal dysfunction in Parkinson's disease. Science. 2017;357:1255-61.

189. Plotegher N, Duchen MR. Crosstalk between lysosomes and mitochondria in parkinson's disease. Front Cell Dev Biol. 2017;5:110.

190. Cisneros J, Belton TB, Shum GC, Molakal CG, Wong YC. Mitochondria-lysosome contact site dynamics and misregulation in neurodegenerative diseases. Trends Neurosci. 2022;45:312-22.

191. Verhoeven K, De Jonghe P, Coen K, et al. Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am J Hum Genet. 2003;72:722-7.

192. Cleeter MW, Chau KY, Gluck C, et al. Glucocerebrosidase inhibition causes mitochondrial dysfunction and free radical damage. Neurochem Int. 2013;62:1-7.

193. Osellame LD, Rahim AA, Hargreaves IP, et al. Mitochondria and quality control defects in a mouse model of Gaucher disease-links to Parkinson's disease. Cell Metab. 2013;17:941-53.

194. Li H, Ham A, Ma TC, et al. Mitochondrial dysfunction and mitophagy defect triggered by heterozygous GBA mutations. Autophagy. 2019;15:113-30.

195. Yang J, Guo Q, Feng X, Liu Y, Zhou Y. Mitochondrial dysfunction in cardiovascular diseases: potential targets for treatment. Front Cell Dev Biol. 2022;10:841523.

196. Arruda AP, Pers BM, Parlakgül G, Güney E, Inouye K, Hotamisligil GS. Chronic enrichment of hepatic endoplasmic reticulum-mitochondria contact leads to mitochondrial dysfunction in obesity. Nat Med. 2014;20:1427-35.

197. Madreiter-Sokolowski CT, Waldeck-Weiermair M, Bourguignon MP, et al. Enhanced inter-compartmental Ca2+ flux modulates mitochondrial metabolism and apoptotic threshold during aging. Redox Biol. 2019;20:458-66.

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

199. 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.

200. Di Micco R, Krizhanovsky V, Baker D, d'Adda di Fagagna F. Cellular senescence in ageing: from mechanisms to therapeutic opportunities. Nat Rev Mol Cell Biol. 2021;22:75-95.

201. Chou SM, Yen YH, Yuan F, Zhang SC, Chong CM. Neuronal senescence in the aged brain. Aging Dis. 2023;14:1618-32.

202. Englund DA, Zhang X, Aversa Z, LeBrasseur NK. Skeletal muscle aging, cellular senescence, and senotherapeutics: current knowledge and future directions. Mech Ageing Dev. 2021;200:111595.

203. Sun M, Jiang W, Mu N, Zhang Z, Yu L, Ma H. Mitochondrial transplantation as a novel therapeutic strategy for cardiovascular diseases. J Transl Med. 2023;21:347.

204. Yamada Y, Maruyama M, Kita T, Usami SI, Kitajiri SI, Harashima H. The use of a MITO-Porter to deliver exogenous therapeutic RNA to a mitochondrial disease's cell with a A1555G mutation in the mitochondrial 12S rRNA gene results in an increase in mitochondrial respiratory activity. Mitochondrion. 2020;55:134-44.

205. Renteln M. A synthetic mitochondrial-based vector for therapeutic purposes. Med Hypotheses. 2018;117:28-30.

206. Magalhães Rebelo AP, Dal Bello F, Knedlik T, et al. Chemical modulation of mitochondria-endoplasmic reticulum contact sites. Cells. 2020;9:1637.

207. Dentoni G, Castro-Aldrete L, Naia L, Ankarcrona M. The potential of small molecules to modulate the mitochondria-endoplasmic reticulum interplay in Alzheimer's disease. Front Cell Dev Biol. 2022;10:920228.

208. Dietel E, Brobeil A, Delventhal L, Tag C, Gattenlöhner S, Wimmer M. Crosstalks of the PTPIP51 interactome revealed in Her2 amplified breast cancer cells by the novel small molecule LDC3/Dynarrestin. PLoS One. 2019;14:e0216642.

209. Franco A, Kitsis RN, Fleischer JA, et al. Correcting mitochondrial fusion by manipulating mitofusin conformations. Nature. 2016;540:74-9.

210. Naia L, Ly P, Mota SI, et al. The Sigma-1 receptor mediates pridopidine rescue of mitochondrial function in huntington disease models. Neurotherapeutics. 2021;18:1017-38.

211. Salvatore T, Galiero R, Caturano A, et al. Effects of metformin in heart failure: from pathophysiological rationale to clinical evidence. Biomolecules. 2021;11:1834.

212. Gao J, Chen G, He H, et al. Therapeutic effects of breviscapine in cardiovascular diseases: a review. Front Pharmacol. 2017;8:289.

213. Zhang QY, Pan Y, Wang R, et al. Quercetin inhibits AMPK/TXNIP activation and reduces inflammatory lesions to improve insulin signaling defect in the hypothalamus of high fructose-fed rats. J Nutr Biochem. 2014;25:420-8.

214. Wang AL, Iadecola C, Wang G. New generations of dihydropyridines for treatment of hypertension. J Geriatr Cardiol. 2017;14:67-72.

215. Kobayashi S, Yano M, Suetomi T, et al. Dantrolene, a therapeutic agent for malignant hyperthermia, markedly improves the function of failing cardiomyocytes by stabilizing interdomain interactions within the ryanodine receptor. J Am Coll Cardiol. 2009;53:1993-2005.

216. Wüst RCI, Coolen BF, Held NM, et al. The antibiotic doxycycline impairs cardiac mitochondrial and contractile function. Int J Mol Sci. 2021;22:4100.

217. Houtkooper RH, Mouchiroud L, Ryu D, et al. Mitonuclear protein imbalance as a conserved longevity mechanism. Nature. 2013;497:451-7.

218. Chiao YA, Kolwicz SC, Basisty N, et al. Rapamycin transiently induces mitochondrial remodeling to reprogram energy metabolism in old hearts. Aging. 2016;8:314-27.

219. Lee DJW, Hodzic Kuerec A, Maier AB. Targeting ageing with rapamycin and its derivatives in humans: a systematic review. Lancet Healthy Longev. 2024;5:e152-62.

220. 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.

221. Liu S, Faitg J, Tissot C, et al. Urolithin A provides cardioprotection and mitochondrial quality enhancement preclinically and improves human cardiovascular health biomarkers. iScience. 2025;28:111814.

222. Gao X, Nan Y, Zhao Y, et al. Atorvastatin reduces lipid accumulation in the liver by activating protein kinase A-mediated phosphorylation of perilipin 5. Biochim Biophys Acta Mol Cell Biol Lipids. 2017;1862:1512-9.

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/