تأثیر تمرین تناوبی شدید بر بیومارکرهای اتوفاژی عضله اسکلتی در موش های نر سالمند

نوع مقاله : مقاله پژوهشی

نویسندگان

گروه تربیت بدنی و علوم ورزشی، واحد بجنورد، دانشگاه آزاد اسلامی، بجنورد، ایران

چکیده

مقدمه و هدف: اتوفاژی نقش مهمی در فرایند سالمندی ایفا می کند. تمرینات ورزشی به عنوان یکی از مهم ترین تعدیل کننده های سالمندی شناخته شده اند، با این حال آثار تمرینات تناوبی شدید (HIIT) بر شاخص های اتوفاژی کمتر شناخته شده است. از این رو، هدف پژوهش حاضر بررسی اثر HIIT بر مقادیر پروتئینی سیسترین 2، AMPK، beclin1 و ULK1 در عضله اسکلتی موش‌های نر سالمند بود.
مواد و روش ها: 20 سر موش نر سالمند نژاد ویستار (18 ماهه) به‌طور تصادفی به دو گروه تجربی و کنترل تقسیم شدند. پس از برآورد حداکثر سرعت، موش ها در گروه‌ تجربی در هشت هفته تمرینات تناوبی شدید دویدن روی تردمیل (8-5 مرحله فعالیت 2 دقیقه‌ای با شدت معادل 80 تا 100 درصد اکسیژن مصرفی بیشینه و با دوره‌های استراحتی فعال 2 دقیقه‌ای با شدت معادل 50 درصد اکسیژن مصرفی بیشینه)، 5 جلسه در هفته شرکت کردند. نمونه های بافت عضله دوقلو جهت اندازه گیری سطوح پروتئینی شاخص های مورد بررسی 48 ساعت پس از آخرین جلسه تمرین استخراج شد. جهت تجزیه وتحلیل داده ها از آزمون تی مستقل در سطح معنی دار 05/0>P استفاده شد.
نتایج: نتایج حاصل از آزمون تی مستقل نشان داد که اجرای هشت هفته HIIT با افزایش معنی دار مقادیر پروتئینی سیسترین 2 (01/0P=)، AMPK فسفریله (005/0P=)، beclin1 (001/0P=) و ULK1 (03/0P=) در گروه HIIT در مقایسه با گروه کنترل همراه بود.
نتیجه‌گیری: به نظر می رسد HIIT می تواند به واسطه تأثیر بر مسیر سیسترین-2/ AMPK، نقش تنظیمی در اتوفاژی داشته باشد و پیشرفت تغییرات همراه با سالمندی در عضله اسکلتی موش های سالمند را تعدیل کند.

کلیدواژه‌ها

عنوان مقاله [English]

The effect of high intensity interval training on skeletal muscle autophagy biomarkers in male elderly rats

نویسندگان [English]

  • Saghar delshad
  • Ali yaghoubi
  • Najme rezaeian
Department of Physical Education and Sport Science, Bojnourd Branch, Islamic Azad University, Bojnourd, Iran
چکیده [English]

Background and Objective: Autophagy plays an important role in the aging process. Exercise is known to be one of the most important modulators of aging; however, the effects of high-intensity interval training (HIIT) on autophagy are not well known. Therefore, this study aimed to investigate the effect of HIIT on protein levels of sestrin 2, AMPK, beclin1 and ULK1 in skeletal muscle of elderly rats.
Materials and Methods: Twenty-old male Wistar rats (18 months) were randomly divided into experimental and control groups. After estimating the maximum speed, rats in the experimental group participated in 8 weeks of high-intensity interval training of running on the treadmill (5-8 sets of running for 2 minutes at an intensity of 80-100 VO2Max with rest intervals of running for 2 minutes at an intensity of 50 VO2Max) five sessions per week. Skeletal muscle tissue samples were extracted 48 hours after the last training session to measure protein levels of factors assessed. An independent t-test was used to analyze the data and p < 0.05 was considered significant.
Results: HIIT resulted in a significant increase in protein levels of sestrin 2 (P=0.01), p-AMPK (P=0.005), beclin1 (P=0.001), and ULK1 (P=0.03) in the experimental group compared to control one.
Conclusion: It seems that HIIT can play a regulatory role in autophagy through the sestrin 2 / AMPK pathway and modulate subsequent progression of changes associated with aging in the skeletal muscle of elderly rats.

کلیدواژه‌ها [English]

  • High Intensity
  • Interval training
  • Autophagy
  • Sestrin 2
  • elderly rat

مراجع

  1. Candow DG, Chilibeck PD. Differences in size, strength, and power of upper and lower body muscle groups in young and older men. The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 2005;60(2):148-56. doi: 10.1093/gerona/60.2.148.
  2. Lauretani F, Russo CR, Bandinelli S, Bartali B, Cavazzini C, Di Iorio A, et al. Age-associated changes in skeletal muscles and their effect on mobility: an operational diagnosis of sarcopenia. Journal of Applied Physiology 2003;95(5):1851-60. doi: 10.1152/japplphysiol.00246.2003.
  3. Zhou J, Freeman TA, Ahmad F, Shang X, Mangano E, Gao E, et al. GSK-3α is a central regulator of age-related pathologies in mice. The Journal of Clinical Investigation 2013;123(4):1821-32. doi: 10.1172/JCI64398.
  4. Bonaldo P, Sandri M. Cellular and molecular mechanisms of muscle atrophy. Disease Models & Mechanisms 2013;6(1):25-39. doi: 10.1242/dmm.010389.
  5. Terman A, Brunk UT. Oxidative stress, accumulation of biological'garbage', and aging. Antioxidants & Redox Signaling 2006;8(1-2):197-204. doi: 10.1089/ars.2006.8.197.
  6. Jiao J, Demontis F. Skeletal muscle autophagy and its role in sarcopenia and organismal aging. Current Opinion in Pharmacology 2017;34:1-6. doi: 10.1016/j.coph.2017.03.009

  7. 45
     
    Lee JH, Budanov AV, Karin M. Sestrins orchestrate cellular metabolism to attenuate aging. Cell Metabolism 2013;18(6):792-801. doi: 10.1016/j.cmet.2013.08.018.
  8. Segalés J, Perdiguero E, Serrano AL, Sousa-Victor P, Ortet L, Jardí M, et al. Sestrin prevents atrophy of disused and aging muscles by integrating anabolic and catabolic signals. Nature Communications 2020;11(1):189. doi: 10.1038/s41467-019-13832-9.
  9. Bae SH, Sung SH, Oh SY, Lim JM, Lee SK, Park YN, et al. Sestrins activate Nrf2 by promoting p62-dependent autophagic degradation of Keap1 and prevent oxidative liver damage. Cell Metabolism 2013;17(1):73-84 doi: 10.1038/s41467-019-13832-9..
  10. Lee JH, Budanov AV, Talukdar S, Park EJ, Park HL, Park H-W, et al. Maintenance of metabolic homeostasis by Sestrin2 and Sestrin3. Cell Metabolism. 2012;16(3):311-21. doi: 10.1016/j.cmet.2012.08.004.
  11. Pilli M, Arko-Mensah J, Ponpuak M, Roberts E, Master S, Mandell MA, et al. TBK-1 promotes autophagy-mediated antimicrobial defense by controlling autophagosome maturation. Immunity. 2012;37(2):223-34. doi: 10.1016/j.immuni.2012.04.015.
  12. Ichimura Y, WaguriS, Sou Y-s, Kageyama S, Hasegawa J, Ishimura R, et al. Phosphorylation of p62 activates the Keap1-Nrf2 pathway during selective autophagy. Molecular Cell 2013;51(5):618-31. doi: 10.1016/j.molcel.2013.08.003.
  13. Ro SH, Semple IA, Park H, Park H, Park HW, Kim M, et al. Sestrin2 promotes Unc‐51‐like kinase 1 mediated phosphorylation of p62/sequestosome‐1. The FEBS Journal 2014;281(17):3816-27. doi: 10.1111/febs.12905.
  14. Kumar A, Shaha C. SESN2 facilitates mitophagy by helping Parkin translocation through ULK1 mediated Beclin1 phosphorylation. Scientific Reports 2018; 12;8(1):615. doi: 10.1038/s41598-017-19102-2.
  15. Lane JD, Korolchuk VI, Murray JT, Zachari M, Ganley IG. The mammalian ULK1 complex and autophagy initiation. Essays in Biochemistry 2017;61(6):585-96. doi: 10.1042/EBC20170021.
  16. Xie Y, Kang R, Tang D. Role of the Beclin 1 Network in the Cross-Regulation Between Autophagy and Apoptosis 2016 In book: Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging (pp.75-88). Elsevier. doi: 10.1016/B978-0-12-802937-4.00002-8
  17. Møller AB, Vendelbo MH, Christensen B, Clasen BF, Bak AM, Jørgensen JO, et al. Physical exercise increases autophagic signaling through ULK1 in human skeletal muscle. Journal of Applied Physiology. 2015;118(8):971-9. doi: 10.1152/japplphysiol.01116.2014.
  18. Jamart C, Francaux M, Millet GY, Deldicque L, Frère D, Féasson L. Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running. Journal of Applied Physiology. 2012;112(9):1529-37. doi: 10.1152/japplphysiol.00952.2011.

  19. 46
     
    Lira VA, Okutsu M, Zhang M, Greene NP, Laker RC, Breen DS, et al. Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance.  The Federation of American Societies for Experimental Biology Journal 2013;27(10):4184-93. doi: 10.1096/fj.13-228486.
  20. Brandt N, Gunnarsson TP, Bangsbo J, Pilegaard H. Exercise and exercise training‐induced increase in autophagy markers in human skeletal muscle. Physiological reports. 2018;6(7):e13651. doi: 10.14814/phy2.13651.
  21. Ju J-s, Jeon S-i, Park J-y, LeeJ-y, Lee S-c, Cho K-j, et al. Autophagy plays a role in skeletal muscle mitochondrial biogenesis in an endurance exercise-trained condition. The Journal of Physiological Sciences. 2016;66(5):417-30 doi: 10.1007/s12576-016-0440-9..
  22. Kim YA, Kim YS, Oh SL, Kim HJ, Song W. Autophagic response to exercise training in skeletal muscle with age. Journal of Physiology and Biochemistry 2013;69(4):697-705. doi: 10.1007/s13105-013-0246-7.
  23. Gibala MJ, McGee SL. Metabolic adaptations to short-term high-intensity interval training: a little pain for a lot of gain?. Exercise and Sport Sciences Reviews 2008;36(2):58-63. doi: 10.1097/JES.0b013e318168ec1f.
  24. Gibala MJ, Little JP, MacDonald MJ, Hawley JA. Physiological adaptations to low‐volume, high‐intensity interval training in health and disease. The Journal of Physiology 2012;590(5):1077-84. doi: 10.1113/jphysiol.2011.224725.
  25. Little JP, Safdar A, Wilkin GP, Tarnopolsky MA, Gibala MJ. A practical model of low‐volume high‐intensity interval training induces mitochondrial biogenesis in human skeletal muscle: potential mechanisms. The Journal of Physiology 2010;588(6):1011-22. doi: 10.1113/jphysiol.2009.181743.
  26. Little JP, Gillen JB, Percival ME, Safdar A, Tarnopolsky MA, Punthakee Z, et al. Low-volume high-intensity interval training reduces hyperglycemia and increases muscle mitochondrial capacity in patients with type 2 diabetes. Journal of applied physiology. 2011;111(6):1554-60. doi: 10.1152/japplphysiol.00921.2011.
  27. Weng T-P, Huang S-C, Chuang Y-F, Wang J-S. Effects of interval and continuous exercise training on CD4 lymphocyte apoptotic and autophagic responses to hypoxic stress in sedentary men. PloS One 2013;8(11):e80248. doi: 10.1371/journal.pone.0080248.
  28. Ziaaldini MM, Koltai E, Csende Z, Goto S, Boldogh I, Taylor AW, et al. Exercise training increases anabolic and attenuates catabolic and apoptotic processes in aged skeletal muscle of male rats. Experimental Gerontology. 2015;67:9-14. doi: 10.1016/j.exger.2015.04.008.
  29. Hafstad AD, Lund J, Hadler-Olsen E,Höper AC, Larsen TS, Aasum E. High-and moderate-intensity training normalizes ventricular function and mechanoenergetics in mice with diet-induced obesity. Diabetes 2013;62(7):2287-94. doi: 10.2337/db12-1580.
  30. Hafstad AD, Boardman NT, Lund J, Hagve M, Khalid AM, Wisløff U,et al. High intensity interval training alters substrate utilization and reduces oxygen consumption in the heart. Journal of Applied Physiology. 2011;111(5):1235-41. doi: 10.1152/japplphysiol.00594.2011.
  31. Azali Alamdari K, Khalafi M. The effects of high intensity interval training on serumlevels of fgf21 and insulin resistance in obese men. Iranian Journal of Diabetes and Metabolism 2019;18(1):41-8.
  32. Lenhare L, Crisol BM, Silva VR, Katashima CK, Cordeiro AV, Pereira KD, et al. Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice. Experimental Gerontology 2017;97:17-21. doi: 10.1016/j.exger.2017.07.009.
  33. Budanov AV. Stress-responsive sestrins link p53 with redox regulation and mammalian target of rapamycin signaling. Antioxidants & Redox Signaling. 2011; 15(6):1679-90. doi: 10.1089/ars.2010.3530.
  34. Lee JH, Budanov AV, Park EJ, Birse R, Kim TE, Perkins GA, et al. Sestrin as a feedback inhibitor of TOR that prevents age-related pathologies. Science 2010;327(5970):1223-8. doi: 10.1126/science.1182228.
  35. Aronson D, Boppart MD, Dufresne SD, Fielding RA, Goodyear LJ. Exercise stimulates c-Jun NH2Kinase activity and c-Jun transcriptional activity in human skeletal muscle. Biochemical and Biophysical Research Communications 1998;251(1):106-10. doi: 10.1006/bbrc.1998.9435.
  36. Lin J-Y, Kuo W-W, Baskaran R, Kuo C-H, Chen Y-A, Chen WS-T, et al. Swimming exercise stimulates IGF1/PI3K/Akt and AMPK/SIRT1/PGC1α survival signaling to suppress apoptosis and inflammation in aging hippocampus. Aging (Albany NY) 2020;12(8):6852 -6864. doi: 10.18632/aging.103046.

  37. 47
     
    Liu H-W, Chang S-J. Moderate exercise suppresses NF-κB signaling and activates the SIRT1-AMPK-PGC1α Axis to attenuate muscle loss in diabetic db/db mice. Frontiers in Physiology 2018;9:636. doi: 10.3389/fphys.2018.00636
  38. Gibala MJ, McGee SL, Garnham AP, Howlett KF, Snow RJ, Hargreaves M. Brief intense interval exercise activates AMPK and p38 MAPK signaling and increases the expression of PGC-1α in human skeletal muscle. Journal of Applied Physiology 2009;106(3):929-34. doi: 10.1152/japplphysiol.90880.2008.
  39. Khalafi M, Mohebbi H, Symonds ME, Karimi P, Akbari A, Tabari E, et al. The impact of moderate-intensity continuous or high-intensityinterval training on adipogenesis and browning of subcutaneous adipose tissue in obese male rats. Nutrients 2020;12(4):925. doi: 10.3390/nu12040925.
  40. Wang T, Niu Y, Liu S, Yuan H, Liu X, Fu L. Exercise improves glucose uptake in murine myotubes through the AMPKα2-mediated induction of Sestrins. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease 2018;1864(10):3368-77. doi: 10.1016/j.bbadis.2018.07.023.
  41. Tao R, Xiong X, Liangpunsakul S, Dong XC. Sestrin 3 protein enhances hepatic insulin sensitivity by direct activation of the mTORC2-Akt signaling. Diabetes. 2015;64(4):1211-23. doi: 10.2337/db14-0539.

  42. 48
     
    Jäger S, Handschin C, Pierre JS, Spiegelman BM. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1α. Proceedings of the National Academy of Sciences. 2007; 104(29):12017-22. doi: 10.1073/pnas.0705070104.
  43. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metabolism 2005;1(6):361-70. doi: 10.1016/j.cmet.2005.05.004.
  44. Cantó C, Gerhart-Hines Z, Feige JN, Lagouge M, Noriega L, Milne JC, et al. AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity. Nature 2009;458(7241):1056-60. doi: 10.1038/nature07813.
  45. Kim M, Sujkowski A, Namkoong S, Gu B, Cobb T, Kim B, et al. Sestrins are evolutionarily conserved mediators of exercise benefits. Nature Communications 2020; 11(1):190. doi: 10.1038/s41467-019-13442-5.
  46. Zhang D, Wang W, Sun X, Xu D, Wang C, Zhang Q, et al. AMPK regulates autophagy by phosphorylating BECN1 at threonine 388. Autophagy 2016;12(9):1447-59. doi: 10.1080/15548627.2016.1185576.
  47. Liu Y, Nguyen PT, Wang X, Zhao Y, Meacham CE, Zou Z, et al. TLR9 and beclin 1 crosstalk regulates muscle AMPK activation in exercise. Nature 2020;578(7796):605-9. doi: 10.1038/s41586-020-1992-7.
  48. Liu W, Xia Y, Kuang H, Wang Z, Liu S, Tang C, et al. Proteomic profile of carbonylated proteins screen the regulation of calmodulin-dependent protein kinases-AMPK-Beclin1in aerobic exercise-induced autophagy in middle-aged rat hippocampus. Gerontology 2019;65(6):620-33 doi: 10.1159/000500742.
دانشور پزشکی
دوره 28، شماره 6 - شماره پیاپی 151
بهمن و اسفند 1399
صفحه 37-48

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