Mechanisms of regulation of apoptosis in skeletal muscles: the effect of physical activity and bioactive compounds



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Abstract

Apoptosis, or programmed cell death, plays a crucial role in maintaining skeletal muscle homeostasis. However, its dysregulation in obesity, type 2 diabetes, and aging leads to accelerated muscle degeneration, reduced functionality, and metabolic disorders. This review examines the mechanisms of apoptosis regulation in skeletal muscles and the impact of two key factors: physical exercise and natural bioactive compounds. Scientific evidence confirms that both physical activity and natural products, such as resveratrol, curcumin, and quercetin, exert significant anti-apoptotic effects by reducing oxidative stress, improving mitochondrial function, and modulating the Bcl-2 and AMPK/SIRT1 signaling pathways. When combined, these interventions exhibit a synergistic effect, making them a promising approach for preventing and treating sarcopenia, obesity, and related metabolic diseases. Despite promising experimental findings, further clinical trials are needed to optimize exercise protocols and determine the most effective combinations of natural compounds to prevent muscle atrophy and enhance metabolic health in patients.

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References

  1. Dedov I.I., Shestakova M.V., Melnichenko G.A., et al. Interdisciplinary clinical practice guidelines "management of obesity and its comorbidities". Obesity and metabolism. 2021;18(1):5-99. (In Russ.) https://doi.org/10.14341/omet12714
  2. Dalili D, Bazzocchi A, Dalili DE, et al. . The role of body composition assessment in obesity and eating disorders. Eur J Radiol. 2020;131:109227. doi: 10.1016/j.ejrad.2020.109227.
  3. Lingvay I, Cohen RV, Roux CWL, Sumithran P. Obesity in adults. Lancet. 2024;404(10456):972-987. doi: 10.1016/S0140-6736(24)01210-8.
  4. Bondareva E.A., Troshina E.A. Obesity. Reasons, features and prospects. Obesity and metabolism. 2024;21(2):174-187. (In Russ.) https://doi.org/10.14341/omet13055
  5. Razina A.O., Achkasov E.E., Runenko S.D. Obesity: the modern approach to the problem. Obesity and metabolism. 2016;13(1):3-8. (In Russ.) https://doi.org/10.14341/omet201613-8
  6. Anekwe CV, Jarrell AR, Townsend MJ, Gaudier GI, Hiserodt JM, Stanford FC. Socioeconomics of Obesity. Curr Obes Rep. 2020;9(3):272-279. doi: 10.1007/s13679-020-00398-7.
  7. Mustafina S.V., Vinter D.A., Alferova V.I. Influence of obesity on the formation and development of cancer. Obesity and metabolism. Obesity and metabolism. 2024;21(2):205-214. (In Russ.) https://doi.org/10.14341/omet13025
  8. Anekwe CV, Jarrell AR, Townsend MJ, Gaudier GI, Hiserodt JM, Stanford FC. Socioeconomics of Obesity. Curr Obes Rep. 2020;9(3):272-279. doi: 10.1007/s13679-020-00398-7.
  9. Keane KN, Cruzat VF, Carlessi R, et al. Molecular Events Linking Oxidative Stress and Inflammation to Insulin Resistance and β-Cell Dysfunction. Oxid Med Cell Longev. 2015;2015:181643. doi: 10.1155/2015/181643.
  10. Röszer T. Adipose Tissue Immunometabolism and Apoptotic Cell Clearance. Cells. 2021;10(9):2288. doi: 10.3390/cells10092288.
  11. Wondmkun YT. Obesity, Insulin Resistance, and Type 2 Diabetes: Associations and Therapeutic Implications. Diabetes Metab Syndr Obes. 2020;13:3611-3616. doi: 10.2147/DMSO.S275898.
  12. Kyazimova ND, Kornyakova VV. Influence of polyphenolic compounds on human health and the course of a number of diseases. Scientific Bulletin of the Omsk State Medical University. 2024;4(1):87-91. doi: 10.61634/2782-3024-2024-13-87-91
  13. de Oliveira MR, Nabavi SF, Manayi A, et al. Resveratrol and the mitochondria: From triggering the intrinsic apoptotic pathway to inducing mitochondrial biogenesis, a mechanistic view. Biochim Biophys Acta. 2016;1860(4):727-45. doi: 10.1016/j.bbagen.2016.01.017.
  14. Liu X, Zhao H, Jin Q, et al. Resveratrol induces apoptosis and inhibits adipogenesis by stimulating the SIRT1-AMPKα-FOXO1 signalling pathway in bovine intramuscular adipocytes. Mol Cell Biochem. 2018;439(1-2):213-223. doi: 10.1007/s11010-017-3149-z.
  15. Shirinsky I.V., Shirinsky V.S., Filatova K.Yu. Efficacy and safety of curcumin in patients with metabolic phenotype of osteoarthritis: A pilot study. Medical Immunology (In Russ.). 2023;25(5):1099-1102. https://doi.org/10.15789/1563-0625-EAS-2771
  16. Xia ZH, Zhang SY, Chen YS, et al. Curcumin anti-diabetic effect mainly correlates with its anti-apoptotic actions and PI3K/Akt signal pathway regulation in the liver. Food Chem Toxicol. 2020;146:111803. doi: 10.1016/j.fct.2020.111803.
  17. Accattato F, Greco M, Pullano SA, et al. Effects of acute physical exercise on oxidative stress and inflammatory status in young, sedentary obese subjects. PLoS One. 2017;12(6):e0178900. doi: 10.1371/journal.pone.0178900.
  18. Zhang X, Gao F. Exercise improves vascular health: Role of mitochondria. Free Radic Biol Med. 2021;177:347-359. doi: 10.1016/j.freeradbiomed.2021.11.002.
  19. Ghoweba RE, Khowailed AA, Aboulhoda BE, et al. Synergistic role of resveratrol and exercise training in management of diabetic neuropathy and myopathy via SIRT1/NGF/GAP43 linkage. Tissue Cell. 2023;81:102014. doi: 10.1016/j.tice.2023.102014.
  20. Liao ZY, Chen JL, Xiao MH, et al. The effect of exercise, resveratrol or their combination on Sarcopenia in aged rats via regulation of AMPK/Sirt1 pathway. Exp Gerontol. 2017;98:177-183. doi: 10.1016/j.exger.2017.08.032.
  21. Nagata I, Kawashima M, Miyazaki A, et al. Icing after skeletal muscle injury with necrosis in a small fraction of myofibers limits inducible nitric oxide synthase-expressing macrophage invasion and facilitates muscle regeneration. Am J Physiol Regul Integr Comp Physiol. 2023;324(4):R574-R588. doi: 10.1152/ajpregu.00258.2022.
  22. Argilés JM, Busquets S, Stemmler B, López-Soriano FJ. Cachexia and sarcopenia: mechanisms and potential targets for intervention. Curr Opin Pharmacol. 2015;22:100-6. doi: 10.1016/j.coph.2015.04.003.
  23. Chen TH, Koh KY, Lin KM, Chou CK. Mitochondrial Dysfunction as an Underlying Cause of Skeletal Muscle Disorders. Int J Mol Sci. 2022;23(21):12926. doi: 10.3390/ijms232112926.
  24. Li W, Sang H, Xu X, et al.. Protective effect of dihydromyricetin on vascular smooth muscle cell apoptosis induced by hydrogen peroxide in rats. Perfusion. 2023;38(3):491-500. doi: 10.1177/02676591211059901.
  25. Sahoo G, Samal D, Khandayataray P, Murthy MK. A Review on Caspases: Key Regulators of Biological Activities and Apoptosis. Mol Neurobiol. 2023;60(10):5805-5837. doi: 10.1007/s12035-023-03433-5.
  26. Means RE, Katz SG. Balancing life and death: BCL-2 family members at diverse ER-mitochondrial contact sites. FEBS J. 2022;289(22):7075-7112. doi: 10.1111/febs.16241.
  27. Mailloux RJ. An Update on Mitochondrial Reactive Oxygen Species Production. Antioxidants (Basel). 2020;9(6):472. doi: 10.3390/antiox9060472.
  28. Napolitano G, Fasciolo G, Venditti P. Mitochondrial Management of Reactive Oxygen Species. Antioxidants (Basel). 2021;10(11):1824. doi: 10.3390/antiox10111824.
  29. Collins KH, Herzog W, MacDonald GZ, et al. Obesity, Metabolic Syndrome, and Musculoskeletal Disease: Common Inflammatory Pathways Suggest a Central Role for Loss of Muscle Integrity. Front Physiol. 2018;9:112. doi: 10.3389/fphys.2018.00112.
  30. Jin JY, Wei XX, Zhi XL, et al. Drp1-dependent mitochondrial fission in cardiovascular disease. Acta Pharmacol Sin. 2021;42(5):655-664. doi: 10.1038/s41401-020-00518-y.
  31. Yapa NMB, Lisnyak V, Reljic B, Ryan MT. Mitochondrial dynamics in health and disease. FEBS Lett. 2021;595(8):1184-1204. doi: 10.1002/1873-3468.14077.
  32. Berns S.A., Sheptulina A.F., Mamutova E.M., et al. Sarcopenic obesity: epidemiology, pathogenesis and diagnostic criteria. Cardiovascular Therapy and Prevention. 2023;22(6):3576. (In Russ.) https://doi.org/10.15829/1728-8800-2023-3576.
  33. Abrigo J, Rivera JC, Aravena J, et al. High Fat Diet-Induced Skeletal Muscle Wasting Is Decreased by Mesenchymal Stem Cells Administration: Implications on Oxidative Stress, Ubiquitin Proteasome Pathway Activation, and Myonuclear Apoptosis. Oxid Med Cell Longev. 2016;2016:9047821. doi: 10.1155/2016/9047821.
  34. Reynaud O, Wang J, Ayoub MB, et al. The impact of high-fat feeding and parkin overexpression on skeletal muscle mass, mitochondrial respiration, and H2O2 emission. Am J Physiol Cell Physiol. 2023;324(2):C366-C376. doi: 10.1152/ajpcell.00388.2022.
  35. Larsson L, Degens H, Li M, et al. Sarcopenia: Aging-Related Loss of Muscle Mass and Function. Physiol Rev. 2019;99(1):427-511. doi: 10.1152/physrev.00061.2017.
  36. Merz KE, Thurmond DC. Role of Skeletal Muscle in Insulin Resistance and Glucose Uptake. Compr Physiol. 2020;10(3):785-809. doi: 10.1002/cphy.c190029.
  37. Ou MY, Zhang H, Tan PC, et al. Adipose tissue aging: mechanisms and therapeutic implications. Cell Death Dis. 2022;13(4):300. doi: 10.1038/s41419-022-04752-6
  38. Dungan CM, Li J, Williamson DL. Caloric Restriction Normalizes Obesity-Induced Alterations on Regulators of Skeletal Muscle Growth Signaling. Lipids. 2016;51(8):905-12. doi: 10.1007/s11745-016-4168-3.
  39. Sishi B, Loos B, Ellis B, et al. Diet-induced obesity alters signalling pathways and induces atrophy and apoptosis in skeletal muscle in a prediabetic rat model. Exp Physiol. 2011;96(2):179-93. doi: 10.1113/expphysiol.2010.054189.
  40. Yuzefovych LV, Musiyenko SI, Wilson GL, Rachek LI. Mitochondrial DNA damage and dysfunction, and oxidative stress are associated with endoplasmic reticulum stress, protein degradation and apoptosis in high fat diet-induced insulin resistance mice. PLoS One. 2013;8(1):e54059. doi: 10.1371/journal.pone.0054059.
  41. Turpin SM, Lancaster GI, Darby I, et al. Apoptosis in skeletal muscle myotubes is induced by ceramides and is positively related to insulin resistance. Am J Physiol Endocrinol Metab. 2006;291(6):E1341-50. doi: 10.1152/ajpendo.00095.2006
  42. Peterson JM, Bryner RW, Alway SE. Satellite cell proliferation is reduced in muscles of obese Zucker rats but restored with loading. Am J Physiol Cell Physiol. 2008; 295(2):C521-8. doi: 10.1152/ajpcell.00073.2008.
  43. Peterson JM, Bryner RW, Sindler A, et al. Mitochondrial apoptotic signaling is elevated in cardiac but not skeletal muscle in the obese Zucker rat and is reduced with aerobic exercise. J Appl Physiol (1985). 2008;105(6):1934-43. doi: 10.1152/japplphysiol.00037.2008.
  44. Romantsova T.R., Sych Yu.P. Immunometabolism and metainflammation in obesity. Obesity and metabolism. 2019;16(4):3-17. (In Russ.) https://doi.org/10.14341/omet12218
  45. Vazeille E, Slimani L, Claustre A, et al. Curcumin treatment prevents increased proteasome and apoptosome activities in rat skeletal muscle during reloading and improves subsequent recovery. J Nutr Biochem. 2012;23(3):245-51. doi: 10.1016/j.jnutbio.2010.11.021.
  46. Lee DY, Chun YS, Kim JK, et al. Curcumin Attenuates Sarcopenia in Chronic Forced Exercise Executed Aged Mice by Regulating Muscle Degradation and Protein Synthesis with Antioxidant and Anti-inflammatory Effects. J Agric Food Chem. 2021;69(22):6214-6228. doi: 10.1021/acs.jafc.1c00699.
  47. Sin TK, Yu AP, Yung BY, et al.. Effects of long-term resveratrol-induced SIRT1 activation on insulin and apoptotic signalling in aged skeletal muscle. Acta Diabetol. 2015;52(6):1063-75. doi: 10.1007/s00592-015-0767-3.
  48. Wu J-P. Resveratrol attenuates obesity- and aging-induced sarcopenia mitochondrial dysfunction in mice skeletal muscle. FASEB J. 2020; 34(S1):1–1
  49. Wang D, Sun H, Song G, et al. Resveratrol Improves Muscle Atrophy by Modulating Mitochondrial Quality Control in STZ-Induced Diabetic Mice. Mol Nutr Food Res. 2018;62(9):e1700941. doi: 10.1002/mnfr.201700941.
  50. Aslan A, Beyaz S, Gok O, Erman O. The effect of ellagic acid on caspase-3/bcl-2/Nrf-2/NF-kB/TNF-α /COX-2 gene expression product apoptosis pathway: a new approach for muscle damage therapy. Mol Biol Rep. 2020;47(4):2573-2582. doi: 10.1007/s11033-020-05340-7.
  51. Wang D, Yang Y, Zou X, et al. Antioxidant Apigenin Relieves Age-Related Muscle Atrophy by Inhibiting Oxidative Stress and Hyperactive Mitophagy and Apoptosis in Skeletal Muscle of Mice. J Gerontol A Biol Sci Med Sci. 2020;75(11):2081-2088. doi: 10.1093/gerona/glaa214.
  52. Le NH, Kim CS, Park T, et al. Quercetin protects against obesity-induced skeletal muscle inflammation and atrophy. Mediators Inflamm. 2014;2014:834294. doi: 10.1155/2014/834294.
  53. Chen C, Yang JS, Lu CC, et al. Effect of Quercetin on Dexamethasone-Induced C2C12 Skeletal Muscle Cell Injury. Molecules. 2020;25(14):3267. doi: 10.3390/molecules25143267.
  54. Tabata S, Aizawa M, Kinoshita M, et al. The influence of isoflavone for denervation-induced muscle atrophy. Eur J Nutr. 2019;58(1):291-300. doi: 10.1007/s00394-017-1593-x.
  55. Mallardo M, Daniele A, Musumeci G, Nigro E. A Narrative Review on Adipose Tissue and Overtraining: Shedding Light on the Interplay among Adipokines, Exercise and Overtraining. Int J Mol Sci. 2024;25(7):4089. doi: 10.3390/ijms25074089.
  56. Taherkhani S, Valaei K, Arazi H, Suzuki K. An Overview of Physical Exercise and Antioxidant Supplementation Influences on Skeletal Muscle Oxidative Stress. Antioxidants (Basel). 2021;10(10):1528. doi: 10.3390/antiox10101528.
  57. Nikawa T, Ulla A, Sakakibara I. Polyphenols and Their Effects on Muscle Atrophy and Muscle Health. Molecules. 2021;26(16):4887. doi: 10.3390/molecules26164887.
  58. Fernández-Sánchez A, Madrigal-Santillán E, Bautista M, et al. Inflammation, oxidative stress, and obesity. Int J Mol Sci. 2011;12(5):3117-32. doi: 10.3390/ijms12053117.
  59. Heo JW, No MH, Cho J, et al. Moderate aerobic exercise training ameliorates impairment of mitochondrial function and dynamics in skeletal muscle of high-fat diet-induced obese mice. FASEB J. 2021;35(2):e21340. doi: 10.1096/fj.202002394R.
  60. Kim HJ, Kwon O. Aerobic exercise prevents apoptosis in skeletal muscles of high-fat-fed ovariectomized rats. Phys Act Nutr. 2022;26(2):1-7. doi: 10.20463/pan.2022.0007.
  61. Cho DK, Choi DH, Cho JY. Effect of treadmill exercise on skeletal muscle autophagy in rats with obesity induced by a high-fat diet. J Exerc Nutrition Biochem. 2017;21(3):26-34. doi: 10.20463/jenb.2017.0013.
  62. Lee SD, Shyu WC, Cheng IS, et al. Effects of exercise training on cardiac apoptosis in obese rats. Nutr Metab Cardiovasc Dis. 2013;23(6):566-73. doi: 10.1016/j.numecd.2011.11.002.
  63. Pattanakuhar S, Sutham W, Sripetchwandee J, et al. Combined exercise and calorie restriction therapies restore contractile and mitochondrial functions in skeletal muscle of obese-insulin resistant rats. Nutrition. 2019;62:74-84. doi: 10.1016/j.nut.2018.11.031.
  64. Wohlgemuth SE, Seo AY, Marzetti E, et al. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol. 2010;45(2):138-48. doi: 10.1016/j.exger.2009.11.002.
  65. Di Meo S, Napolitano G, Venditti P. Mediators of Physical Activity Protection against ROS-Linked Skeletal Muscle Damage. Int J Mol Sci. 2019;20(12):3024. doi: 10.3390/ijms20123024.
  66. Sharma VK, Singh TG, Singh S, Garg N, Dhiman S. Apoptotic Pathways and Alzheimer's Disease: Probing Therapeutic Potential. Neurochem Res. 2021;46(12):3103-3122. doi: 10.1007/s11064-021-03418-7.
  67. Veras ASC, Correia RR, Batista VRG, et al. Aerobic physical exercise modifies the prostate tumoral environment. Life Sci. 2023;332:122097. doi: 10.1016/j.lfs.2023.122097.
  68. Naoi M, Wu Y, Shamoto-Nagai M, Maruyama W. Mitochondria in Neuroprotection by Phytochemicals: Bioactive Polyphenols Modulate Mitochondrial Apoptosis System, Function and Structure. Int J Mol Sci. 2019;20(10):2451. doi: 10.3390/ijms20102451.
  69. Yan Z, Lira VA, Greene NP. Exercise training-induced regulation of mitochondrial quality. Exerc Sport Sci Rev. 2012;40(3):159-64. doi: 10.1097/JES.0b013e3182575599.
  70. Forbes-Hernández TY, Giampieri F, Gasparrini M, et al. The effects of bioactive compounds from plant foods on mitochondrial function: a focus on apoptotic mechanisms. Food Chem Toxicol. 2014;68:154-82. doi: 10.1016/j.fct.2014.03.017.
  71. Slavin MB, Khemraj P, Hood DA. Exercise, mitochondrial dysfunction and inflammasomes in skeletal muscle. Biomed J. 2024;47(1):100636. doi: 10.1016/j.bj.2023.100636.
  72. Shehata AH, Anter AF, Ahmed AF. Role of SIRT1 in sepsis-induced encephalopathy: Molecular targets for future therapies. Eur J Neurosci. 2023;58(10):4211-4235. doi: 10.1111/ejn.16167.
  73. Yang L, Liu D, Jiang S, et al. SIRT1 signaling pathways in sarcopenia: Novel mechanisms and potential therapeutic targets. Biomed Pharmacother. 2024;177:116917. doi: 10.1016/j.biopha.2024.116917.
  74. Zhang T, Xu L, Guo X, et al. The potential of herbal drugs to treat heart failure: The roles of Sirt1/AMPK. J Pharm Anal. 2024;14(2):157-176. doi: 10.1016/j.jpha.2023.09.001

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СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ЭЛ № ФС 77 - 80650 от 15.03.2021 г.