Turkiye Klinikleri Journal of Sports Sciences

.: REVIEW
Which Exercise Type is Better on Autophagy in Older Adults?
Yaşlı Bireylerde Hangi Egzersiz Türü Otofaji İçin Daha İyidir?
Gülşah ŞAHİNa, Bilgetekin Burak GÜNARb, Ali COŞKUNc
aDepartment of Coaching Education, Çanakkale Onsekiz Mart University Faculty of Sport Sciences, Çanakkale, TURKEY
bDepartment of Physical Education and Sports Teaching, Çanakkale Onsekiz Mart University Faculty of Sport Sciences, Çanakkale, TURKEY
cDepartment of Sports Management, Çanakkale Onsekiz Mart University Vocational School of Bayramiç, Çanakkale, TURKEY
Turkiye Klinikleri J Sports Sci. 2021;13(1):124-32
doi: 10.5336/sportsci.2020-77058
Article Language: EN
Full Text
ABSTRACT
 Aging is characterized by accumulation of damage in cellular components increasing fragility and risk of death caused by disruption of different biological processes. The autophagy is a basic cellular homeostasis process requiring different pathophysiologic conditions for degradation and recycling of damaged cellular organelles and proteins. This process, called autophagy, is a fundamental cellular homeostatic process required in different pathophysiological conditions for the degradation and recycling of damaged cellular organelles and proteins. During the aging process, the autophagy flux reduces. However, both animal and human studies show that exercise has positive effects on autophagy markers and flux within aging metabolism. The aim of this review is to answer a few questions such as ''Which exercise stimulates autophagy more in aging?'', ''What do the available human research results indicate?'', ''How does aging affect autophagy?'', ''What is the correlation between exercise, aging, autophagy and muscle mass?''. According to the research results, resistance exercises and endurance exercises affect autophagy in the aging process. Resistance exercises increase the autophagy flux and may prevent sarcopenia. Endurance exercises increase oxidative stress, which may increase autophagy flux and preserve mitochondria quality. There is a need for new studies to more clearly reveal the effects of both exercise types. However, it is well known at present that whatever exercise is performed, obesity, chronic diseases, menopause, initial autophagy level and content, fitness levels of elderly individuals, training status, mitochondria content, muscle mass and nutrition type may change the progress of autophagy

Keywords: Otofaji; yaşlanma; egzersiz; sarkopeni; hücre; mitokondri
ÖZET
 Yaşlanma, farklı biyolojik süreçlerin bozulmasından kaynaklanan kırılganlığı ve ölüm riskini artıran hücresel bileşenlerde hasar birikimi ile karakterizedir. Hücre içinde meydana gelen yıkım olayları sayesinde organizmanın ihtiyacının kalmadığı hasara uğramış organeller, sitoplazmik parçalar ve birikmiş proteinler ortadan kaldırılır. Otofaji olarak adlandırılan bu süreç, hasarlı hücresel organellerin ve proteinlerin bozulması ve geri dönüşümü için farklı patofizyolojik koşullarda gerekli olan temel bir hücresel homeostatik süreçtir. Yaşlanma sürecinde otofaji akışı azalmaktadır. Fakat hem hayvan hem de insan çalışmaları, yaşlanan metabolizma üzerinde egzersizin otofaji belirteçleri ve akışı üzerindeki olumlu etkileri olduğunu göstermektedir. Bu derlemenin amacı; ''Yaşlanmada hangi egzersiz otofajiyi daha çok harekete geçirir?'' ''Mevcut insan araştırmalarının sonuçları neyi işaret etmektedir?'', ''Yaşlanma otofajiyi nasıl etkiler?'', ''Egzersiz, yaşlanma, otofaji ve kas kütlesi arasındaki ilişki nedir?'' sorularını mevcut araştırmalara göre yanıtlamaktır. Araştırma sonuçlarına göre direnç egzersizleri ve dayanıklılık egzersizleri, yaşlanma sürecindeki otofajiyi etkiler. Direnç egzersizleri otofaji akışını artırarak, sarkopeniyi önleyebilir. Dayanıklılık egzersizleri, oksidatif stresi artırarak, otofaji akışını artırabilir ve mitokondri kalitesini koruyabilir. Her iki egzersiz türünün etkilerinin daha net ortaya çıkarılması için yeni çalışmalara ihtiyaç vardır. Ancak şu anda iyi bilinmektedir ki hangi egzersiz yapılırsa yapılsın, obezite, kronik hastalıklar, menopoz, başlangıç otofaji düzeyi ve içeriği, yaşlı bireyin kondisyon düzeyi, antrenman durumu, mitokondri içeriği, sahip olduğu kas kütlesi ve beslenme türü otofajinin seyrini değiştirebilecektir.

Anahtar Kelimeler: Autophagy; aging; exercise; sarcopenia; cell; mitochondria
REFERENCES:
  1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-217.[Crossref] [PubMed] [PMC] 
  2. Ren J, Zhang Y. Targeting autophagy in aging and aging-related cardiovascular diseases. Trends Pharmacol Sci. 2018;39(12):1064-76.[Crossref] [PubMed] [PMC] 
  3. Tian H, Chen P, Ren J. Physical exercise, autophagy and cardiometabolic stress in aging. Aging (Albany NY). 2019;11(15):5287-8.[Crossref] [PubMed] [PMC] 
  4. Toraman F, Sahin G. Age responses to multicomponent training programme in older adults. Disabil Rehabil. 2004;26(8):448-54.[Crossref] [PubMed] 
  5. Toraman NF, Erman A, Agyar E. Effects of multicomponent training on functional fitness in older adults. J Aging Phys Act. 2004;12(4):538-53.[Crossref] [PubMed] 
  6. Ohsumi Y. Historical landmarks of autophagy research. Cell Res. 2014;24(1):9-23.[Crossref] [PubMed] [PMC] 
  7. Tam BT, Siu PM. Autophagic cellular responses to physical exercise in skeletal muscle. Sports Med. 2014;44(5):625-40.[Crossref] [PubMed] 
  8. White JP, Billin AN, Campbell ME, Russell AJ, Huffman KM, Kraus WE. The AMPK/p27Kip1 Axis Regulates Autophagy/Apoptosis Decisions in Aged Skeletal Muscle Stem Cells. Stem Cell Reports. 2018;11(2):425-39.[Crossref] [PubMed] [PMC] 
  9. Mejías-Pe-a Y, Rodriguez-Miguelez P, Fernandez-Gonzalo R, Martínez-Flórez S, Almar M, de Paz JA, et al. Effects of aerobic training on markers of autophagy in the elderly. Age (Dordr). 2016;38(2):33.[Crossref] [PubMed] [PMC] 
  10. García-Prat L, Martínez-Vicente M, Perdiguero E, Ortet L, Rodríguez-Ubreva J, Rebollo E, et al. Autophagy maintains stemness by preventing senescence. Nature. 2016;529(7584):37-42.[Crossref] [PubMed] 
  11. Cuervo AM, Macian F. Autophagy and the immune function in aging. Curr Opin Immunol. 2014;29:97-104.[Crossref] [PubMed] [PMC] 
  12. Huang J, Xu J, Pang S, Bai B, Yan B. Age-related decrease of the LAMP-2 gene expression in human leukocytes. Clin Biochem. 2012;45(15):1229-32.[Crossref] [PubMed] 
  13. Shou J, Chen PJ, Xiao WH. Mechanism of increased risk of insulin resistance in aging skeletal muscle. Diabetol Metab Syndr. 2020;12:14.[Crossref] [PubMed] [PMC] 
  14. Carnio S, LoVerso F, Baraibar MA, Longa E, Khan MM, Maffei M, et al. Autophagy impairment in muscle induces neuromuscular junction degeneration and precocious aging. Cell Rep. 20141;8(5):1509-21.[Crossref] [PubMed] [PMC] 
  15. Choi AM, Ryter SW, Levine B. Autophagy in human health and disease. N Engl J Med. 2013;368(7):651-62.[Crossref] [PubMed] 
  16. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell. 2010;140(3):313-26.[Crossref] [PubMed] [PMC] 
  17. Peker N, Gozuacik D. Autophagy as a cellular stress response mechanism in the nervous system. J Mol Biol. 2020;432(8):2560-88.[Crossref] [PubMed] 
  18. Salminen A, Vihko V. Autophagic response to strenuous exercise in mouse skeletal muscle fibers. Virchows Arch B Cell Pathol Incl Mol Pathol. 1984;45(1):97-106.[Crossref] [PubMed] 
  19. Werner CM, Hecksteden A, Morsch A, Zundler J, Wegmann M, Kratzsch J, et al. Differential effects of endurance, interval, and resistance training on telomerase activity and telomere length in a randomized, controlled study. Eur Heart J. 2019;40(1):34-46.[Crossref] [PubMed] [PMC] 
  20. Escobar KA, Cole NH, Mermier CM, VanDusseldorp TA. Autophagy and aging: maintaining the proteome through exercise and caloric restriction. Aging Cell. 2019;18(1):e12876.[Crossref] [PubMed] [PMC] 
  21. Grumati P, Coletto L, Schiavinato A, Castagnaro S, Bertaggia E, Sandri M, et al. Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles. Autophagy. 2011;7(12):1415-23.[Crossref] [PubMed] [PMC] 
  22. Nederveen JP, Joanisse S, Snijders T, Ivankovic V, Baker SK, Phillips SM, et al. Skeletal muscle satellite cells are located at a closer proximity to capillaries in healthy young compared with older men. J Cachexia Sarcopenia Muscle. 2016;7(5):547-54.[Crossref] [PubMed] [PMC] 
  23. Verdijk LB, Gleeson BG, Jonkers RA, Meijer K, Savelberg HH, Dendale P, et al. Skeletal muscle hypertrophy following resistance training is accompanied by a fiber type-specific increase in satellite cell content in elderly men. J Gerontol A Biol Sci Med Sci. 2009;64(3):332-9.[Crossref] [PubMed] [PMC] 
  24. Le Grand F, Rudnicki MA. Skeletal muscle satellite cells and adult myogenesis. Curr Opin Cell Biol. 2007;19(6):628-33.[Crossref] [PubMed] [PMC] 
  25. He C, Klionsky DJ. Regulation mechanisms and signaling pathways of autophagy. Annu Rev Genet. 2009;43:67-93.[Crossref] [PubMed] [PMC] 
  26. Kroemer G, Mari-o G, Levine B. Autophagy and the integrated stress response. Mol Cell. 2010;40(2):280-93.[Crossref] [PubMed] [PMC] 
  27. Wen X, Wu J, Wang F, Liu B, Huang C, Wei Y. Deconvoluting the role of reactive oxygen species and autophagy in human diseases. Free Radic Biol Med. 2013;65:402-10.[Crossref] [PubMed] 
  28. He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature. 2012;481(7382):511-5. Erratum in: Nature. 2013;503(7474):146.[Crossref] [PubMed] [PMC] 
  29. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell. 2008;132(1):27-42.[Crossref] [PubMed] [PMC] 
  30. Knuppertz L, Osiewacz HD. Orchestrating the network of molecular pathways affecting aging: Role of nonselective autophagy and mitophagy. Mech Ageing Dev. 2016;153:30-40.[Crossref] [PubMed] 
  31. Schwalm C, Jamart C, Benoit N, Naslain D, Prémont C, Prévet J, et al. Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation. FASEB J. 2015;29(8):3515-26.[Crossref] [PubMed] 
  32. Sandri M. Autophagy in health and disease. 3. Involvement of autophagy in muscle atrophy. Am J Physiol Cell Physiol. 2010;298(6):C1291-7.[Crossref] [PubMed] 
  33. Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009;10(6):507-15.[Crossref] [PubMed] 
  34. Mooren FC, Krüger K. Exercise, autophagy, and apoptosis. Prog Mol Biol Transl Sci. 2015;135:407-22.[Crossref] [PubMed] 
  35. Li FH, Li T, Su YM, Ai JY, Duan R, Liu TC. Cardiac basal autophagic activity and increased exercise capacity. J Physiol Sci. 2018;68(6):729-42.[Crossref] [PubMed] 
  36. Li FH, Li T, Ai JY, Sun L, Min Z, Duan R, et al. Beneficial autophagic activities, mitochondrial function, and metabolic phenotype adaptations promoted by high-intensity interval training in a rat model. Front Physiol. 2018;9:571.[Crossref] [PubMed] [PMC] 
  37. Park SS, Kwon ES, Kwon KS. Molecular mechanisms and therapeutic interventions in sarcopenia. Osteoporos Sarcopenia. 2017;3(3):117-22.[Crossref] [PubMed] [PMC] 
  38. Marzetti E, Calvani R, Tosato M, Cesari M, Di Bari M, Cherubini A, et al; SPRINTT Consortium. Physical activity and exercise as countermeasures to physical frailty and sarcopenia. Aging Clin Exp Res. 2017;29(1):35-42.[Crossref] [PubMed] 
  39. Lee DE, Bareja A, Bartlett DB, White JP. Autophagy as a therapeutic target to enhance aged muscle regeneration. Cells. 2019;8(2):183.[Crossref] [PubMed] [PMC] 
  40. Park SS, Seo YK, Kwon KS. Sarcopenia targeting with autophagy mechanism by exercise. BMB Rep. 2019;52(1):64-9.[Crossref] [PubMed] [PMC] 
  41. Nederveen JP, Joanisse S, Séguin CM, Bell KE, Baker SK, Phillips SM, et al. The effect of exercise mode on the acute response of satellite cells in old men. Acta Physiol (Oxf). 2015;215(4):177-90.[Crossref] [PubMed] 
  42. Kim YA, Kim YS, Oh SL, Kim HJ, Song W. Autophagic response to exercise training in skeletal muscle with age. J Physiol Biochem. 2013;69(4):697-705.[Crossref] [PubMed] 
  43. Luo L, Lu AM, Wang Y, Hong A, Chen Y, Hu J, et al. Chronic resistance training activates autophagy and reduces apoptosis of muscle cells by modulating IGF-1 and its receptors, Akt/mTOR and Akt/FOXO3a signaling in aged rats. Exp Gerontol. 2013;48(4):427-36.[Crossref] [PubMed] 
  44. Carter HN, Kim Y, Erlich AT, Zarrin-Khat D, Hood DA. Autophagy and mitophagy flux in young and aged skeletal muscle following chronic contractile activity. J Physiol. 2018;596(16):3567-84.[Crossref] [PubMed] [PMC] 
  45. Fry CS, Drummond MJ, Glynn EL, Dickinson JM, Gundermann DM, Timmerman KL, et al. Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Skelet Muscle. 2011;1(1):11.[Crossref] [PubMed] [PMC] 
  46. Fry CS, Drummond MJ, Glynn EL, Dickinson JM, Gundermann DM, Timmerman KL, et al. Skeletal muscle autophagy and protein breakdown following resistance exercise are similar in younger and older adults. J Gerontol A Biol Sci Med Sci. 2013;68(5):599-607.[Crossref] [PubMed] [PMC] 
  47. Jamart C, Benoit N, Raymackers JM, Kim HJ, Kim CK, Francaux M. Autophagy-related and autophagy-regulatory genes are induced in human muscle after ultraendurance exercise. Eur J Appl Physiol. 2012;112(8):3173-7.[Crossref] [PubMed] 
  48. Jiang D, Chen K, Lu X, Gao HJ, Qin ZH, Lin F. Exercise ameliorates the detrimental effect of chloroquine on skeletal muscles in mice via restoring autophagy flux. Acta Pharmacol Sin. 2014;35(1):135-42.[Crossref] [PubMed] [PMC] 
  49. Vainshtein A, Tryon LD, Pauly M, Hood DA. Role of PGC-1α during acute exercise-induced autophagy and mitophagy in skeletal muscle. Am J Physiol Cell Physiol. 2015;308(9):C710-9.[Crossref] [PubMed] [PMC] 
  50. Cuervo AM, Bergamini E, Brunk UT, Dröge W, Ffrench M, Terman A. Autophagy and aging: the importance of maintaining "clean" cells. Autophagy. 2005;1(3):131-40.[Crossref] [PubMed] 
  51. Halling JF, Ringholm S, Olesen J, Prats C, Pilegaard H. Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1α dependent manner. Exp Gerontol. 2017;96:1-6.[Crossref] [PubMed] 
  52. O'Leary MF, Vainshtein A, Iqbal S, Ostojic O, Hood DA. Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle. Am J Physiol Cell Physiol. 2013;304(5):C422-30.[Crossref] [PubMed] 
  53. Russ DW, Krause J, Wills A, Arreguin R. "SR stress" in mixed hindlimb muscles of aging male rats. Biogerontology. 2012;13(5):547-55.[Crossref] [PubMed] 
  54. Fan J, Kou X, Jia S, Yang X, Yang Y, Chen N. Autophagy as a potential target for sarcopenia. J Cell Physiol. 2016;231(7):1450-9.[Crossref] [PubMed] 
  55. Mejías-Pe-a Y, Estébanez B, Rodriguez-Miguelez P, Fernandez-Gonzalo R, Almar M, de Paz JA, et al. Impact of resistance training on the autophagy-inflammation-apoptosis crosstalk in elderly subjects. Aging (Albany NY). 2017;9(2):408-18.[Crossref] [PubMed] [PMC] 
  56. Balan E, Schwalm C, Naslain D, Nielens H, Francaux M, Deldicque L. Regular endurance exercise promotes fission, mitophagy, and oxidative phosphorylation in human skeletal muscle independently of age. Front Physiol. 2019;10:1088.[Crossref] [PubMed] [PMC] 
  57. Glynn EL, Fry CS, Drummond MJ, Dreyer HC, Dhanani S, Volpi E, et al. Muscle protein breakdown has a minor role in the protein anabolic response to essential amino acid and carbohydrate intake following resistance exercise. Am J Physiol Regul Integr Comp Physiol. 2010;299(2):R533-40.[Crossref] [PubMed] [PMC] 
  58. Verdijk LB, Snijders T, Holloway TM, VAN Kranenburg J, VAN Loon LJ. Resistance training increases skeletal muscle capillarization in healthy older men. Med Sci Sports Exerc. 2016;48(11):2157-64.[Crossref] [PubMed] 
  59. Sanchez AM, Bernardi H, Py G, Candau RB. Autophagy is essential to support skeletal muscle plasticity in response to endurance exercise. Am J Physiol Regul Integr Comp Physiol. 2014;307(8):R956-69.[Crossref] [PubMed] 
  60. Li H, Miao W, Ma J, Xv Z, Bo H, Li J, et al. Acute exercise-induced mitochondrial stress triggers an inflammatory response in the myocardium via NLRP3 inflammasome activation with mitophagy. Oxid Med Cell Longev. 2016;2016:1987149.[Crossref] [PubMed] [PMC] 
  61. Peeri M, Amiri S. Protective effects of exercise in metabolic disorders are mediated by inhibition of mitochondrial-derived sterile inflammation. Med Hypotheses. 2015;85(6):707-9.[Crossref] [PubMed] 
  62. Jamart C, Francaux M, Millet GY, Deldicque L, Frère D, Féasson L. Modulation of autophagy and ubiquitin-proteasome pathways during ultra-endurance running. J Appl Physiol (1985). 2012;112(9):1529-37.[Crossref] [PubMed] 
  63. 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. J Appl Physiol (1985). 2015;118(8):971-9.[Crossref] [PubMed] 
  64. Masschelein E, Van Thienen R, D'Hulst G, Hespel P, Thomis M, Deldicque L. Acute environmental hypoxia induces LC3 lipidation in a genotype-dependent manner. FASEB J. 2014;28(2):1022-34.[Crossref] [PubMed] 
  65. Tachtsis B, Smiles WJ, Lane SC, Hawley JA, Camera DM. Acute endurance exercise induces nuclear p53 abundance in human skeletal muscle. Front Physiol. 2016;7:144.[Crossref] [PubMed] [PMC] 
  66. Yan Z, Lira VA, Greene NP. Exercise training-induced regulation of mitochondrial quality. Exerc Sport Sci Rev. 2012;40(3):159-64.[Crossref] [PubMed] [PMC] 
  67. Weng TP, Huang SC, Chuang YF, Wang JS. 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.[Crossref] [PubMed] [PMC] 
  68. Colleluori G, Aguirre L, Phadnis U, Fowler K, Armamento-Villareal R, Sun Z, et al. Aerobic plus resistance exercise in obese older adults improves muscle protein synthesis and preserves myocellular quality despite weight loss. Cell Metab. 2019;30(2):261-73.e6.[Crossref] [PubMed] [PMC] 
  69. Mancini A, Vitucci D, Randers MB, Schmidt JF, Hagman M, Andersen TR, et al. Lifelong football training: effects on autophagy and healthy longevity promotion. Front Physiol. 2019;10:132.[Crossref] [PubMed] [PMC] 
  70. Leon LJ, Gustafsson ÅB. Staying young at heart: autophagy and adaptation to cardiac aging. J Mol Cell Cardiol. 2016;95:78-85.[Crossref] [PubMed] [PMC] 
  71. Proctor DN, Sinning WE, Walro JM, Sieck GC, Lemon PW. Oxidative capacity of human muscle fiber types: effects of age and training status. J Appl Physiol (1985). 1995;78(6):2033-8.[Crossref] [PubMed] 
  72. He C, Sumpter R Jr, Levine B. Exercise induces autophagy in peripheral tissues and in the brain. Autophagy. 2012;8(10):1548-51.[Crossref] [PubMed] [PMC] 
  73. Rubinsztein DC, Mari-o G, Kroemer G. Autophagy and aging. Cell. 2011;146(5):682-95.[Crossref] [PubMed] 
  74. Tomaru U, Takahashi S, Ishizu A, Miyatake Y, Gohda A, Suzuki S, et al. Decreased proteasomal activity causes age-related phenotypes and promotes the development of metabolic abnormalities. Am J Pathol. 2012;180(3):963-72.[Crossref] [PubMed] 
  75. Glick D, Barth S, Macleod KF. Autophagy: cellular and molecular mechanisms. J Pathol. 2010;221(1):3-12.[Crossref] [PubMed] [PMC] 
  76. Vissing K, McGee S, Farup J, Kjølhede T, Vendelbo M, Jessen N. Differentiated mTOR but not AMPK signaling after strength vs endurance exercise in training-accustomed individuals. Scand J Med Sci Sports. 2013;23(3):355-66.[Crossref] [PubMed] 
  77. Dethlefsen MM, Halling JF, Møller HD, Plomgaard P, Regenberg B, Ringholm S, et al. Regulation of apoptosis and autophagy in mouse and human skeletal muscle with aging and lifelong exercise training. Exp Gerontol. 2018;111:141-53.[Crossref] [PubMed] 
  78. Siu PM, Bryner RW, Martyn JK, Alway SE. Apoptotic adaptations from exercise training in skeletal and cardiac muscles. FASEB J. 2004;18(10):1150-2.[Crossref] [PubMed] 
  79. 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. FASEB J. 2013;27(10):4184-93.[Crossref] [PubMed] [PMC] 
  80. Lo Verso F, Carnio S, Vainshtein A, Sandri M. Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity. Autophagy. 2014;10(11):1883-94.[Crossref] [PubMed] [PMC] 
  81. Martin-Rincon M, Morales-Alamo D, Calbet JAL. Exercise-mediated modulation of autophagy in skeletal muscle. Scand J Med Sci Sports. 2018;28(3):772-81.[Crossref] [PubMed] 
  82. Zampieri S, Pietrangelo L, Loefler S, Fruhmann H, Vogelauer M, Burggraf S, et al. Lifelong physical exercise delays age-associated skeletal muscle decline. J Gerontol A Biol Sci Med Sci. 2015;70(2):163-73.[Crossref] [PubMed] 
  83. Drummond MJ, Addison O, Brunker L, Hopkins PN, McClain DA, LaStayo PC, et al. Downregulation of E3 ubiquitin ligases and mitophagy-related genes in skeletal muscle of physically inactive, frail older women: a cross-sectional comparison. J Gerontol A Biol Sci Med Sci. 2014;69(8):1040-8.[Crossref] [PubMed] [PMC] 
  84. Akın Ş, Demirel HA. [Sarcopenia and exercise training]. Turkiye Klinikleri J Sports Med-Special Topics. 2017;3(2):136-42.[Link] 

.: Up To Date

.: Process List

Login

 Forgot your password?

 New Registration  

Contact

Ortadoğu Reklam Tanıtım Yayıncılık Turizm Eğitim İnşaat Sanayi ve Ticaret A.Ş.

.: Address

Turkocagi Caddesi No:30 06520 Balgat / ANKARA
Phone: +90 312 286 56 56
Fax: +90 312 220 04 70
E-mail: info@turkiyeklinikleri.com

.: Manuscript Editing Department

Phone: +90 312 286 56 56/ 2
E-mail: yaziisleri@turkiyeklinikleri.com

.: English Language Redaction

Phone: +90 312 286 56 56/ 145
E-mail: tkyayindestek@turkiyeklinikleri.com

.: Marketing Sales-Project Department

Phone: +90 312 286 56 56/ 142
E-mail: reklam@turkiyeklinikleri.com

.: Subscription and Public Relations Department

Phone: +90 312 286 56 56/ 118
E-mail: abone@turkiyeklinikleri.com

.: Customer Services

Phone: +90 312 286 56 56/ 118
E-mail: satisdestek@turkiyeklinikleri.com

1. TERMS OF USE

1.1. To use the web pages with http://www.turkiyeklinikleri.com domain name or the websites reached through the sub domain names attached to the domain name (They will be collectively referred as "SITE"), please read the conditions below. If you do not accept these terms, please cease to use the "SITE." "SITE" owner reserves the right to change the information on the website, forms, contents, the "SITE," "SITE" terms of use anytime they want.

1.2. The owner of the "SITE" is Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. (From now on it is going to be referred as "Turkiye Klinikleri", shortly) and it resides at Turkocagi cad. No:30, 06520 Balgat Ankara. The services in the "SITE" are provided by "Turkiye Klinikleri."

1.3. Anyone accessing the "SITE" with or without a fee whether they are a natural person or a legal identity is considered to agree these terms of use. In this contract hereby, "Turkiye Klinikleri" may change the stated terms anytime. These changes will be published in the "SITE" periodically and they will be valid when they are published. Any natural person or legal identity benefiting from and reaching to the "SITE" are considered to be agreed to any change on hereby contract terms done by "Turkiye Klinikleri."

1.4. The "Terms of Use" hereby is published in the website with the last change on March 30th 2014 and the "SITE" is activated by enabling the access to everyone. The "Terms of Use" hereby is also a part of the any "USER Contract" was and/or will be done with the users using "Turkiye Klinikleri" services with or without a fee an inseparable.

2. DEFINITIONS

2.1. "SITE": A website offering different kind of services and context with a certain frame determined by "Turkiye Klinikleri" and it is accessible on-line on http://www.turkiyeklinikleri.com domain name and/or subdomains connected to the domain name.

2.2. USER: A natural person or a legal identity accessing to the "SITE" through online settings.

2.3. LINK: A link enabling to access to another website through the "SITE", the files, the context or through another website to the "SITE", the files and the context.

2.4. CONTEXT: Any visual, literary and auditory images published in the "Turkiye Klinikleri", "SITE" and/or any website or any accessible information, file, picture, number/figures, price, etc.

2.5. "USER CONTRACT": An electronically signed contract between a natural or a legal identity benefiting from special services "Turkiye Klinikleri" will provide and "Turkiye Klinikleri".

3. SCOPE OF THE SERVICES

3.1. "Turkiye Klinikleri" is completely free to determine the scope and quality of the services via the "SITE".

3.2. To benefit the services of "Turkiye Klinikleri" "SITE", the "USER" must deliver the features that will be specified by "Turkiye Klinikleri". "Turkiye Klinikleri" may change this necessity any time single-sided.

3.3. Not for a limited number, the services "Turkiye Klinikleri" will provide through the "SITE" for a certain price or for free are;

- Providing scientific articles, books and informative publications for health industry.

- Providing structural, statistical and editorial support to article preparation stage for scientific journals.

4. GENERAL PROVISIONS

4.1. "Turkiye Klinikleri" is completely free to determine which of the services and contents provided in the "SITE" will be charged.

4.2. People benefiting from the services provided by "Turkiye Klinikleri" and using the website can use the "SITE" only according to the law and only for personal reasons. Users have the criminal and civil liability for every process and action they take in the "SITE". Every USER agrees, declares and undertakes that they will not proceed by any function or action infringement of rights of "Turkiye Klinikleri"s and/or other third parties', they are the exclusive right holder on usage, processing, storage, made public and revealing any written, visual or auditory information reported to Turkiye Klinikleri" and/or "SITE" to the third parties. "USER" agrees and undertakes that s/he will not duplicate, copy, distribute, process, the pictures, text, visual and auditory images, video clips, files, databases, catalogs and lists within the "SITE", s/he will not be using these actions or with other ways to compete with "Turkiye Klinikleri", directly or indirectly.

4.3. The services provided and the context published within the "SITE" by third parties is not under the responsibility of "Turkiye Klinikleri", institutions collaborated with "Turkiye Klinikleri", "Turkiye Klinikleri" employee and directors, "Turkiye Klinikleri" authorized salespeople. Commitment to accuracy and legality of the published information, context, visual and auditory images provided by any third party are under the full responsibility of the third party. "Turkiye Klinikleri" does not promise and guarantee the safety, accuracy and legality of the services and context provided by a third party.

4.4. "USER"s cannot act against "Turkiye Klinikleri", other "USER"s and third parties by using the "SITE". "Turkiye Klinikleri" has no direct and/or indirect responsibility for any damage a third party suffered or will suffer regarding "USER"s actions on the "SITE" against the rules of the hereby "Terms of Use" and the law.

4.5. "USER"s accept and undertake that the information and context they provided to the "SITE" are accurate and legal. "Turkiye Klinikleri" is not liable and responsible for promising and guaranteeing the verification of the information and context transmitted to "Turkiye Klinikleri" by the "USER"s, or uploaded, changed and provided through the "SITE" by them and whether these information are safe, accurate and legal.

4.6. "USER"s agree and undertake that they will not perform any action leading to unfair competition, weakening the personal and commercial credit of "Turkiye Klinikleri" and a third party,  encroaching and attacking on personal rights within the "SITE" in accordance with the Turkish Commercial Code Law.

4.7. "Turkiye Klinikleri" reserves the right to change the services and the context within the "SITE"  anytime. "Turkiye Klinikleri" may use this right without any notification and timelessly. "USER"s have to make the changes and/or corrections "Turkiye Klinikleri" required immediately. Any changes and/or corrections that are required by "Turkiye Klinikleri", may be made by "Turkiye Klinikleri" when needed. Any harm, criminal and civil liability resulted or will result from changes and/or corrections required by "Turkiye Klinikleri" and were not made on time by the "USER"s belongs completely to the users.

4.8. "Turkiye Klinikleri" may give links through the "SITE" to other websites and/or "CONTEXT"s and/or folders that are outside of their control and owned and run by third parties. These links are provided for ease of reference only and do not hold qualification for support the respective web SITE or the admin or declaration or guarantee for the information inside. "Turkiye Klinikleri" does not hold any responsibility over the web-sites connected through the links on the "SITE", folders and context, the services or products on the websites provided through these links or their context.

4.9. "Turkiye Klinikleri" may use the information provided to them by the "USERS" through the "SITE" in line with the terms of the "PRIVACY POLICY" and "USER CONTRACT". It may process the information or classify and save them on a database. "Turkiye Klinikleri" may also use the USER's or visitor's identity, address, e-mail address, phone number, IP number, which sections of the "SITE" they visited, domain type, browser type, date and time information to provide statistical evaluation and customized services.

5. PROPRIETARY RIGHTS

5.1. The information accessed through this "SITE" or provided by the users legally and all the elements (including but not limited to design, text, image, html code and other codes) of the "SITE" (all of them will be called as studies tied to "Turkiye Klinikleri"s copyrights) belongs to "Turkiye Klinikleri". Users do not have the right to resell, process, share, distribute, display or give someone permission to access or to use the "Turkiye Klinikleri" services, "Turkiye Klinikleri" information and the products under copyright protection by "Turkiye Klinikleri". Within hereby "Terms of Use" unless explicitly permitted by "Turkiye Klinikleri" nobody can reproduce, process, distribute or produce or prepare any study from those under "Turkiye Klinikleri" copyright protection.

5.2. Within hereby "Terms of Use", "Turkiye Klinikleri" reserves the rights for "Turkiye Klinikleri" services, "Turkiye Klinikleri" information, the products associated with "Turkiye Klinikleri" copyrights, "Turkiye Klinikleri" trademarks, "Turkiye Klinikleri" trade looks or its all rights for other entity and information it has through this website unless it is explicitly authorized by "Turkiye Klinikleri".

6. CHANGES IN THE TERMS OF USE

"Turkiye Klinikleri" in its sole discretion may change the hereby "Terms of Use" anytime announcing within the "SITE". The changed terms of the hereby "Terms of Use" will become valid when they are announced. Hereby "Terms of Use" cannot be changed by unilateral declarations of users.

7. FORCE MAJEURE

"Turkiye Klinikleri" is not responsible for executing late or never of this hereby "Terms of Use", privacy policy and "USER Contract" in any situation legally taken into account as force majeure. Being late or failure of performance or non-defaulting of this and similar cases like this will not be the case from the viewpoint of "Turkiye Klinikleri", and "Turkiye Klinikleri" will not have any damage liability for these situations. "Force majeure" term will be regarded as outside of the concerned party's reasonable control and any situation that "Turkiye Klinikleri" cannot prevent even though it shows due diligence. Also, force majeure situations include but not limited to natural disasters, rebellion, war, strike, communication problems, infrastructure and internet failure, power cut and bad weather conditions.

8. LAW AND AUTHORISATION TO FOLLOW

Turkish Law will be applied in practicing, interpreting the hereby "Terms of Use" and managing the emerging legal relationships within this "Terms of Use" in case of finding element of foreignness, except for the rules of Turkish conflict of laws. Ankara Courts and Enforcement Offices are entitled in any controversy happened or may happen due to hereby contract.

9. CLOSING AND AGREEMENT

Hereby "Terms of Use" come into force when announced in the "SITE" by "Turkiye Klinikleri". The users are regarded to agree to hereby contract terms by using the "SITE". "Turkiye Klinikleri" may change the contract terms and the changes will be come into force by specifying the version number and the date of change on time it is published in the "SITE".

 

30.03.2014

Privacy Policy

We recommend you to read the terms of use below before you visit our website. In case you agree these terms, following our rules will be to your favor. Please read our Terms of Use thoroughly.

www.turkiyeklinikleri.com website belongs to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. and is designed in order to inform physicians in the field of health

www.turkiyeklinikleri.com cannot reach to user’s identity, address, service providers or other information. The users may send this information to the website through forms if they would like to. However, www.turkiyeklinikleri.com may collect your hardware and software information. The information consists of your IP address, browser type, operating system, domain name, access time, and related websites. www.turkiyeklinikleri.com cannot sell the provided user information (your name, e-mail address, home and work address, phone number) to the third parties, publish it publicly, or keep it in the website. Gathered information has a directing feature to be a source for the website’s visitor profile, reporting and promotion of the services.

www.turkiyeklinikleri.com uses the taken information:

-To enhance, improve and maintain the quality of the website

-To generate visitor’s profile and statistical data

-To determine the tendency of the visitors on using our website

-To send print publications/correspondences

-To send press releases or notifications through e-mail

-To generate a list for an event or competition

By using www.turkiyeklinikleri.com you are considered to agree that;

-Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. cannot be hold responsible for any user’s illegal and immoral behavior,

-Terms of use may change from time to time,

-It is not responsible for other websites’ contents it cannot control or the harms they may cause although it uses the connection they provided.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. may block the website to users in the following events:

-Information with wrong, incomplete, deceiving or immoral expressions is recorded to the website,

-Proclamation, advertisement, announcement, libelous expressions are used against natural person or legal identity,

-During various attacks to the website,

-Disruption of the website because of a virus.

Written, visual and audible materials of the website, including the code and the software are under protection by legal legislation.

Without the written consent of Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. the information on the website cannot be downloaded, changed, reproduced, copied, republished, posted or distributed.

All rights of the software and the design of the website belong to Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc.

Ortadoğu Advertisement Presentation Publishing Tourism Education Architecture Industry and Trade Inc. will be pleased to hear your comments about our terms of use. Please share the subjects you think may enrich our website or if there is any problem regarding our website.

info@turkiyeklinikleri.com