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Effects of aging and exercise training on mitochondrial function and apoptosis in the rat heart

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Abstract

Aging is associated with vulnerability to cardiovascular diseases, and mitochondrial dysfunction plays a critical role in cardiovascular disease pathogenesis. Exercise training is associated with benefits against chronic cardiac diseases. The purpose of this study was to determine the effects of aging and treadmill exercise training on mitochondrial function and apoptosis in the rat heart. Fischer 344 rats were divided into young sedentary (YS; n = 10, 4 months), young exercise (YE; n = 10, 4 months), old sedentary (OS; n = 10, 20 months), and old exercise (OE; n = 10, 20 months) groups. Exercise training groups ran on a treadmill at 15 m/min (young) or 10 m/min (old), 45 min/day, 5 days/week for 8 weeks. Morphological parameters, mitochondrial function, mitochondrial dynamics, mitophagy, and mitochondria-mediated apoptosis were analyzed in cardiac muscle. Mitochondrial O2 respiratory capacity and Ca2+ retention capacity gradually decreased, and mitochondrial H2O2 emitting potential significantly increased with aging. Exercise training attenuated aging-induced mitochondrial H2O2 emitting potential and mitochondrial O2 respiratory capacity, while protecting Ca2+ retention in the old groups. Aging triggered imbalanced mitochondrial dynamics and excess mitophagy, while exercise training ameliorated the aging-induced imbalance in mitochondrial dynamics and excess mitophagy. Aging induced increase in Bax and cleaved caspase-3 protein levels, while decreasing Bcl-2 levels. Exercise training protected against the elevation of apoptotic signaling markers by decreasing Bax and cleaved caspase-3 and increasing Bcl-2 protein levels, while decreasing the Bax/Bcl-2 ratio and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive myonuclei. These data demonstrate that regular exercise training prevents aging-induced impairment of mitochondrial function and mitochondria-mediated apoptosis in cardiac muscles.

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References

  1. Abel ED, Doenst T (2011) Mitochondrial adaptations to physiological vs. pathological cardiac hypertrophy. Cardiovasc Res 90:234–242. https://doi.org/10.1093/cvr/cvr015

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Akhmedov AT, Marin-Garcia J (2015) Mitochondrial DNA maintenance: an appraisal. Mol Cell Biochem 409:283–305. https://doi.org/10.1007/s11010-015-2532-x

    Article  CAS  PubMed  Google Scholar 

  3. Anderson EJ, Lustig ME, Boyle KE, Woodlief TL, Kane DA, Lin CT, Price JW 3rd, Kang L, Rabinovitch PS, Szeto HH, Houmard JA, Cortright RN, Wasserman DH, Neufer PD (2009) Mitochondrial H2O2 emission and cellular redox state link excess fat intake to insulin resistance in both rodents and humans. J Clin Invest 119:573–581. https://doi.org/10.1172/JCI37048

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Andreu AL, Arbos MA, Perez-Martos A, Lopez-Perez MJ, Asin J, Lopez N, Montoya J, Schwartz S (1998) Reduced mitochondrial DNA transcription in senescent rat heart. Biochem Biophys Res Commun 252:577–581. https://doi.org/10.1006/bbrc.1998.9703

    Article  CAS  PubMed  Google Scholar 

  5. Aokage T, Ohsawa I, Ohta S (2004) Green fluorescent protein causes mitochondria to aggregate in the presence of the Bcl-2 family proteins. Biochem Biophys Res Commun 314:711–716. https://doi.org/10.1016/j.bbrc.2003.12.152

    Article  CAS  PubMed  Google Scholar 

  6. Bhandari P, Song M, Dorn GW 2nd (2015) Dissociation of mitochondrial from sarcoplasmic reticular stress in Drosophila cardiomyopathy induced by molecularly distinct mitochondrial fusion defects. J Mol Cell Cardiol 80:71–80. https://doi.org/10.1016/j.yjmcc.2014.12.018

    Article  CAS  PubMed  Google Scholar 

  7. Boengler K, Kosiol M, Mayr M, Schulz R, Rohrbach S (2017) Mitochondria and ageing: role in heart, skeletal muscle and adipose tissue. J Cachexia Sarcopenia Muscle 8:349–369. https://doi.org/10.1002/jcsm.12178

    Article  PubMed  PubMed Central  Google Scholar 

  8. Bratic A, Larsson NG (2013) The role of mitochondria in aging. J Clin Invest 123:951–957. https://doi.org/10.1172/JCI64125

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Brenner DA, Apstein CS, Saupe KW (2001) Exercise training attenuates age-associated diastolic dysfunction in rats. Circulation 104:221–226. https://doi.org/10.1161/01.cir.104.2.221

    Article  CAS  PubMed  Google Scholar 

  10. Campos JC, Queliconi BB, Bozi LHM, Bechara LRG, Dourado PMM, Andres AM, Jannig PR, Gomes KMS, Zambelli VO, Rocha-Resende C, Guatimosim S, Brum PC, Mochly-Rosen D, Gottlieb RA, Kowaltowski AJ, Ferreira JCB (2017) Exercise reestablishes autophagic flux and mitochondrial quality control in heart failure. Autophagy 13:1304–1317. https://doi.org/10.1080/15548627.2017.1325062

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Capitanio D, Vasso M, De Palma S, Fania C, Torretta E, Cammarata FP, Magnaghi V, Procacci P, Gelfi C (2016) Specific protein changes contribute to the differential muscle mass loss during ageing. Proteomics 16:645–656. https://doi.org/10.1002/pmic.201500395

    Article  CAS  PubMed  Google Scholar 

  12. Cheng Z, Ito S, Nishio N, Thanasegaran S, Fang H, Isobe K (2013) Characteristics of cardiac aging in C57BL/6 mice. Exp Gerontol 48:341–348. https://doi.org/10.1016/j.exger.2013.01.005

    Article  CAS  PubMed  Google Scholar 

  13. Choksi KB, Papaconstantinou J (2008) Age-related alterations in oxidatively damaged proteins of mouse heart mitochondrial electron transport chain complexes. Free Radic Biol Med 44:1795–1805. https://doi.org/10.1016/j.freeradbiomed.2008.01.032

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Choksi KB, Nuss JE, Deford JH, Papaconstantinou J (2008) Age-related alterations in oxidatively damaged proteins of mouse skeletal muscle mitochondrial electron transport chain complexes. Free Radic Biol Med 45:826–838. https://doi.org/10.1016/j.freeradbiomed.2008.06.006

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dai DF, Chen T, Johnson SC, Szeto H, Rabinovitch PS (2012) Cardiac aging: from molecular mechanisms to significance in human health and disease. Antioxid Redox Signal 16:1492–1526. https://doi.org/10.1089/ars.2011.4179

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. El'darov Ch M, Vays VB, Vangeli IM, Kolosova NG, Bakeeva LE (2015) Morphometric examination of mitochondrial ultrastructure in aging cardiomyocytes. Biochemistry (Mosc) 80:604–609. https://doi.org/10.1134/S0006297915050132

    Article  CAS  Google Scholar 

  17. Feridooni HA, Dibb KM, Howlett SE (2015) How cardiomyocyte excitation, calcium release and contraction become altered with age. J Mol Cell Cardiol 83:62–72. https://doi.org/10.1016/j.yjmcc.2014.12.004

    Article  CAS  PubMed  Google Scholar 

  18. Figueiredo PA, Appell Coriolano HJ, Duarte JA (2014) Cardiac regeneration and cellular therapy: is there a benefit of exercise? Int J Sports Med 35:181–190. https://doi.org/10.1055/s-0033-1351253

    Article  CAS  PubMed  Google Scholar 

  19. Fulda S, Gorman AM, Hori O, Samali A (2010) Cellular stress responses: cell survival and cell death. Int J Cell Biol 2010:214074. https://doi.org/10.1155/2010/214074

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Gazoti Debessa CR, Mesiano Maifrino LB, Rodrigues de Souza R (2001) Age related changes of the collagen network of the human heart. Mech Ageing Dev 122:1049–1058. https://doi.org/10.1016/s0047-6374(01)00238-x

    Article  CAS  PubMed  Google Scholar 

  21. Gioscia-Ryan RA, Battson ML, Cuevas LM, Zigler MC, Sindler AL, Seals DR (2016) Voluntary aerobic exercise increases arterial resilience and mitochondrial health with aging in mice. Aging (Albany NY) 8:2897–2914. https://doi.org/10.18632/aging.101099

    Article  CAS  Google Scholar 

  22. Hafner AV, Dai J, Gomes AP, Xiao CY, Palmeira CM, Rosenzweig A, Sinclair DA (2010) Regulation of the mPTP by SIRT3-mediated deacetylation of CypD at lysine 166 suppresses age-related cardiac hypertrophy. Aging (Albany NY) 2:914–923. https://doi.org/10.18632/aging.100252

    Article  CAS  Google Scholar 

  23. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 11:298–300

    Article  CAS  Google Scholar 

  24. Hoshino A, Mita Y, Okawa Y, Ariyoshi M, Iwai-Kanai E, Ueyama T, Ikeda K, Ogata T, Matoba S (2013) Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart. Nat Commun 4:2308. https://doi.org/10.1038/ncomms3308

    Article  CAS  PubMed  Google Scholar 

  25. Ikeda Y, Shirakabe A, Brady C, Zablocki D, Ohishi M, Sadoshima J (2015) Molecular mechanisms mediating mitochondrial dynamics and mitophagy and their functional roles in the cardiovascular system. J Mol Cell Cardiol 78:116–122. https://doi.org/10.1016/j.yjmcc.2014.09.019

    Article  CAS  PubMed  Google Scholar 

  26. Jin H, Yang R, Li W, Lu H, Ryan AM, Ogasawara AK, Van Peborgh J, Paoni NF (2000) Effects of exercise training on cardiac function, gene expression, and apoptosis in rats. Am J Phys Heart Circ Phys 279:H2994–H3002

    CAS  Google Scholar 

  27. Joseph AM, Adhihetty PJ, Wawrzyniak NR, Wohlgemuth SE, Picca A, Kujoth GC, Prolla TA, Leeuwenburgh C (2013) Dysregulation of mitochondrial quality control processes contribute to sarcopenia in a mouse model of premature aging. PLoS One 8:e69327. https://doi.org/10.1371/journal.pone.0069327

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Kang PM, Yue P, Liu Z, Tarnavski O, Bodyak N, Izumo S (2004) Alterations in apoptosis regulatory factors during hypertrophy and heart failure. Am J Phys Heart Circ Phys 287:H72–H80. https://doi.org/10.1152/ajpheart.00556.2003

    Article  CAS  Google Scholar 

  29. Kolwicz SC Jr, Purohit S, Tian R (2013) Cardiac metabolism and its interactions with contraction, growth, and survival of cardiomyocytes. Circ Res 113:603–616. https://doi.org/10.1161/CIRCRESAHA.113.302095

    Article  CAS  PubMed  Google Scholar 

  30. Konopka AR, Suer MK, Wolff CA, Harber MP (2014) Markers of human skeletal muscle mitochondrial biogenesis and quality control: effects of age and aerobic exercise training. J Gerontol A Biol Sci Med Sci 69:371–378. https://doi.org/10.1093/gerona/glt107

    Article  CAS  PubMed  Google Scholar 

  31. Kwak HB, Song W, Lawler JM (2006) Exercise training attenuates age-induced elevation in Bax/Bcl-2 ratio, apoptosis, and remodeling in the rat heart. FASEB J 20:791–793. https://doi.org/10.1096/fj.05-5116fje

    Article  CAS  PubMed  Google Scholar 

  32. Lawler JM, Powers SK, Visser T, Van Dijk H, Kordus MJ, Ji LL (1993) Acute exercise and skeletal muscle antioxidant and metabolic enzymes: effects of fiber type and age. Am J Phys 265:R1344–R1350. https://doi.org/10.1152/ajpregu.1993.265.6.R1344

    Article  CAS  Google Scholar 

  33. Lenaz G, Bovina C, Castelluccio C, Fato R, Formiggini G, Genova ML, Marchetti M, Pich MM, Pallotti F, Parenti Castelli G, Biagini G (1997) Mitochondrial complex I defects in aging. Mol Cell Biochem 174:329–333

    Article  CAS  Google Scholar 

  34. Lesnefsky EJ, Chen Q, Hoppel CL (2016) Mitochondrial metabolism in aging heart. Circ Res 118:1593–1611. https://doi.org/10.1161/CIRCRESAHA.116.307505

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Liu L, Azhar G, Gao W, Zhang X, Wei JY (1998) Bcl-2 and Bax expression in adult rat hearts after coronary occlusion: age-associated differences. Am J Phys 275:R315–R322

    CAS  Google Scholar 

  36. Liu M, Zhang P, Chen M, Zhang W, Yu L, Yang XC, Fan Q (2012) Aging might increase myocardial ischemia / reperfusion-induced apoptosis in humans and rats. Age (Dordr) 34:621–632. https://doi.org/10.1007/s11357-011-9259-8

    Article  Google Scholar 

  37. Lu L, Guo J, Hua Y, Huang K, Magaye R, Cornell J, Kelly DJ, Reid C, Liew D, Zhou Y, Chen A, Xiao W, Fu Q, Wang BH (2017) Cardiac fibrosis in the ageing heart: contributors and mechanisms. Clin Exp Pharmacol Physiol 44(Suppl 1):55–63. https://doi.org/10.1111/1440-1681.12753

    Article  CAS  PubMed  Google Scholar 

  38. Marin-Garcia J, Akhmedov AT, Moe GW (2013) Mitochondria in heart failure: the emerging role of mitochondrial dynamics. Heart Fail Rev 18:439–456. https://doi.org/10.1007/s10741-012-9330-2

    Article  PubMed  Google Scholar 

  39. Marzetti E, Calvani R, Cesari M, Buford TW, Lorenzi M, Behnke BJ, Leeuwenburgh C (2013) Mitochondrial dysfunction and sarcopenia of aging: from signaling pathways to clinical trials. Int J Biochem Cell Biol 45:2288–2301. https://doi.org/10.1016/j.biocel.2013.06.024

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Miro O, Casademont J, Casals E, Perea M, Urbano-Marquez A, Rustin P, Cardellach F (2000) Aging is associated with increased lipid peroxidation in human hearts, but not with mitochondrial respiratory chain enzyme defects. Cardiovasc Res 47:624–631

    Article  CAS  Google Scholar 

  41. Moreira OC, Estebanez B, Martinez-Florez S, de Paz JA, Cuevas MJ, Gonzalez-Gallego J (2017) Mitochondrial function and mitophagy in the elderly: effects of exercise. Oxidative Med Cell Longev 2017:2012798. https://doi.org/10.1155/2017/2012798

    Article  CAS  Google Scholar 

  42. Navarro A, Boveris A (2007) The mitochondrial energy transduction system and the aging process. Am J Physiol Cell Physiol 292:C670–C686. https://doi.org/10.1152/ajpcell.00213.2006

    Article  CAS  PubMed  Google Scholar 

  43. Ni HM, Williams JA, Ding WX (2015) Mitochondrial dynamics and mitochondrial quality control. Redox Biol 4:6–13. https://doi.org/10.1016/j.redox.2014.11.006

    Article  CAS  PubMed  Google Scholar 

  44. Nitahara JA, Cheng W, Liu Y, Li B, Leri A, Li P, Mogul D, Gambert SR, Kajstura J, Anversa P (1998) Intracellular calcium, DNase activity and myocyte apoptosis in aging Fischer 344 rats. J Mol Cell Cardiol 30:519–535. https://doi.org/10.1006/jmcc.1997.0616

    Article  CAS  PubMed  Google Scholar 

  45. No MH, Heo JW, Yoo SZ, Jo HS, Park DH, Kang JH, Seo DY, Han J, Kwak HB (2018) Effects of aging on mitochondrial hydrogen peroxide emission and calcium retention capacity in rat heart. J Exerc Rehabil 14:920–926. https://doi.org/10.12965/jer.1836550.275

    Article  PubMed  PubMed Central  Google Scholar 

  46. Novoa U, Arauna D, Moran M, Nunez M, Zagmutt S, Saldivia S, Valdes C, Villasenor J, Zambrano CG, Gonzalez DR (2017) High-intensity exercise reduces cardiac fibrosis and hypertrophy but does not restore the nitroso-redox imbalance in diabetic cardiomyopathy. Oxidative Med Cell Longev 2017:7921363. https://doi.org/10.1155/2017/7921363

    Article  CAS  Google Scholar 

  47. Palmer CS, Osellame LD, Laine D, Koutsopoulos OS, Frazier AE, Ryan MT (2011) MiD49 and MiD51, new components of the mitochondrial fission machinery. EMBO Rep 12:565–573. https://doi.org/10.1038/embor.2011.54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Panel M, Ghaleh B, Morin D (2018) Mitochondria and aging: a role for the mitochondrial transition pore? Aging Cell 17:e12793. https://doi.org/10.1111/acel.12793

    Article  CAS  PubMed  Google Scholar 

  49. Picard M, Taivassalo T, Gouspillou G, Hepple RT (2011) Mitochondria: isolation, structure and function. J Physiol 589:4413–4421. https://doi.org/10.1113/jphysiol.2011.212712

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pollack M, Leeuwenburgh C (2001) Apoptosis and aging: role of the mitochondria. J Gerontol A Biol Sci Med Sci 56:B475–B482. https://doi.org/10.1093/gerona/56.11.b475

    Article  CAS  PubMed  Google Scholar 

  51. Preston CC, Oberlin AS, Holmuhamedov EL, Gupta A, Sagar S, Syed RH, Siddiqui SA, Raghavakaimal S, Terzic A, Jahangir A (2008) Aging-induced alterations in gene transcripts and functional activity of mitochondrial oxidative phosphorylation complexes in the heart. Mech Ageing Dev 129:304–312. https://doi.org/10.1016/j.mad.2008.02.010

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Reddy PH (2014) Increased mitochondrial fission and neuronal dysfunction in Huntington’s disease: implications for molecular inhibitors of excessive mitochondrial fission. Drug Discov Today 19:951–955. https://doi.org/10.1016/j.drudis.2014.03.020

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Redza-Dutordoir M, Averill-Bates DA (2016) Activation of apoptosis signalling pathways by reactive oxygen species. Biochim Biophys Acta 1863:2977–2992. https://doi.org/10.1016/j.bbamcr.2016.09.012

    Article  CAS  PubMed  Google Scholar 

  54. Riehle C, Wende AR, Zhu Y, Oliveira KJ, Pereira RO, Jaishy BP, Bevins J, Valdez S, Noh J, Kim BJ, Moreira AB, Weatherford ET, Manivel R, Rawlings TA, Rech M, White MF, Abel ED (2014) Insulin receptor substrates are essential for the bioenergetic and hypertrophic response of the heart to exercise training. Mol Cell Biol 34:3450–3460. https://doi.org/10.1128/MCB.00426-14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Roh J, Rhee J, Chaudhari V, Rosenzweig A (2016) The role of exercise in cardiac aging: from physiology to molecular mechanisms. Circ Res 118:279–295. https://doi.org/10.1161/CIRCRESAHA.115.305250

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Rosca MG, Hoppel CL (2013) Mitochondrial dysfunction in heart failure. Heart Fail Rev 18:607–622. https://doi.org/10.1007/s10741-012-9340-0

    Article  CAS  PubMed  Google Scholar 

  57. Rosca MG, Vazquez EJ, Kerner J, Parland W, Chandler MP, Stanley W, Sabbah HN, Hoppel CL (2008) Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation. Cardiovasc Res 80:30–39. https://doi.org/10.1093/cvr/cvn184

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Shadel GS, Horvath TL (2015) Mitochondrial ROS signaling in organismal homeostasis. Cell 163:560–569. https://doi.org/10.1016/j.cell.2015.10.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Siu PM, Pistilli EE, Butler DC, Alway SE (2005) Aging influences cellular and molecular responses of apoptosis to skeletal muscle unloading. Am J Physiol Cell Physiol 288:C338–C349. https://doi.org/10.1152/ajpcell.00239.2004

    Article  CAS  PubMed  Google Scholar 

  60. Song W, Kwak HB, Lawler JM (2006) Exercise training attenuates age-induced changes in apoptotic signaling in rat skeletal muscle. Antioxid Redox Signal 8:517–528. https://doi.org/10.1089/ars.2006.8.517

    Article  CAS  PubMed  Google Scholar 

  61. Stavrovskaya IG, Kristal BS (2005) The powerhouse takes control of the cell: is the mitochondrial permeability transition a viable therapeutic target against neuronal dysfunction and death? Free Radic Biol Med 38:687–697. https://doi.org/10.1016/j.freeradbiomed.2004.11.032

    Article  CAS  PubMed  Google Scholar 

  62. Steenman M, Lande G (2017) Cardiac aging and heart disease in humans. Biophys Rev 9:131–137. https://doi.org/10.1007/s12551-017-0255-9

    Article  PubMed  PubMed Central  Google Scholar 

  63. Syed M, Skonberg C, Hansen SH (2016) Inhibition of ATP synthesis by fenbufen and its conjugated metabolites in rat liver mitochondria. Toxicol in Vitro 31:23–29. https://doi.org/10.1016/j.tiv.2015.11.013

    Article  CAS  PubMed  Google Scholar 

  64. Takeuchi A, Kim B, Matsuoka S (2015) The destiny of Ca(2+) released by mitochondria. J Physiol Sci 65:11–24. https://doi.org/10.1007/s12576-014-0326-7

    Article  CAS  PubMed  Google Scholar 

  65. Tatarkova Z, Kuka S, Racay P, Lehotsky J, Dobrota D, Mistuna D, Kaplan P (2011) Effects of aging on activities of mitochondrial electron transport chain complexes and oxidative damage in rat heart. Physiol Res 60:281–289

    Article  CAS  Google Scholar 

  66. Tate CA, Helgason T, Hyek MF, McBride RP, Chen M, Richardson MA, Taffet GE (1996) SERCA2a and mitochondrial cytochrome oxidase expression are increased in hearts of exercise-trained old rats. Am J Phys 271:H68–H72. https://doi.org/10.1152/ajpheart.1996.271.1.H68

    Article  CAS  Google Scholar 

  67. Trifunovic A, Larsson NG (2008) Mitochondrial dysfunction as a cause of ageing. J Intern Med 263:167–178. https://doi.org/10.1111/j.1365-2796.2007.01905.x

    Article  CAS  PubMed  Google Scholar 

  68. Vasquez-Trincado C, Garcia-Carvajal I, Pennanen C, Parra V, Hill JA, Rothermel BA, Lavandero S (2016) Mitochondrial dynamics, mitophagy and cardiovascular disease. J Physiol 594:509–525. https://doi.org/10.1113/JP271301

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Westermann B (2010) Mitochondrial fusion and fission in cell life and death. Nat Rev Mol Cell Biol 11:872–884. https://doi.org/10.1038/nrm3013

    Article  CAS  PubMed  Google Scholar 

  70. Youle RJ, Narendra DP (2011) Mechanisms of mitophagy. Nat Rev Mol Cell Biol 12:9–14. https://doi.org/10.1038/nrm3028

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. Zorov DB, Juhaszova M, Sollott SJ (2014) Mitochondrial reactive oxygen species (ROS) and ROS-induced ROS release. Physiol Rev 94:909–950. https://doi.org/10.1152/physrev.00026.2013

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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This work was supported by the Ministry of Education of the Republic of Korea and the National Research Foundation of Korea (NRF-2016S1A5A8018954).

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  1. Department of Kinesiology, Inha University, 100 Inha-ro, Michuhol-gu, Incheon, 22212, Republic of Korea

    Mi-Hyun No, Jun-Won Heo, Su-Zi Yoo, Dong-Ho Park & Hyo-Bum Kwak

  2. Department of Physiology, Kyung Hee University, Seoul, South Korea

    Chang-Ju Kim

  3. Department of Pharmacology and Medicinal Toxicology Research Center, Inha University School of Medicine, Incheon, South Korea

    Ju-Hee Kang

  4. Department of Physiology and Cardiovascular and Metabolic Disease Center, Inje University School of Medicine, Busan, South Korea

    Dae-Yun Seo & Jin Han

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This article is part of the special issue on Exercise Physiology: future opportunities and challenges in Pflügers Archiv—European Journal of Physiology

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No, MH., Heo, JW., Yoo, SZ. et al. Effects of aging and exercise training on mitochondrial function and apoptosis in the rat heart. Pflugers Arch - Eur J Physiol 472, 179–193 (2020). https://doi.org/10.1007/s00424-020-02357-6

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