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Sarcopenia targeting with autophagy mechanism by exercise

  • Park, Sung Sup (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Seo, Young-Kyo (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)) ;
  • Kwon, Ki-Sun (Aging Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB))
  • Received : 2018.10.30
  • Published : 2019.01.31

Abstract

The loss of skeletal muscle, called sarcopenia, is an inevitable event during the aging process, and significantly impacts quality of life. Autophagy is known to reduce muscle atrophy caused by dysfunctional organelles, even though the molecular mechanism remains unclear. Here, we have discuss the current understanding of exercise-induced autophagy activation in skeletal muscle regeneration and remodeling, leading to sarcopenia intervention. With aging, dysregulation of autophagy flux inhibits lysosomal storage processes involved in muscle biogenesis. AMPK-ULK1 and the $FoxO/PGC-1{\alpha}$ signaling pathways play a critical role in the induction of autophagy machinery in skeletal muscle, thus these pathways could be targets for therapeutics development. Autophagy has been also shown to be a critical regulator of stem cell fate, which determines satellite cell differentiation into muscle fiber, thereby increasing muscle mass. This review aims to provide a comprehensive understanding of the physiological role of autophagy in skeletal muscle aging and sarcopenia.

Keywords

References

  1. Masiero E, Agatea L, Mammucari C et al (2009) Autophagy is required to maintain muscle mass. Cell metab 10, 507-515 https://doi.org/10.1016/j.cmet.2009.10.008
  2. Park SS, Kwon E-S and Kwon K-S (2017) Molecular mechanisms and therapeutic interventions in sarcopenia. Osteoporosis and Sarcopenia 3, 117-122 https://doi.org/10.1016/j.afos.2017.08.098
  3. Kwak JY, Hwang H, Kim SK et al (2018) Prediction of sarcopenia using a combination of multiple serum biomarkers. Sci Rep 8, 8574 https://doi.org/10.1038/s41598-018-26617-9
  4. Mordier S, Deval C, Bechet D, Tassa A and Ferrara M (2000) Leucine limitation induces autophagy and activation of lysosome-dependent proteolysis in C2C12 myotubes through a mammalian target of rapamycin- independent signaling pathway. J Biol Chem 275, 29900-29906 https://doi.org/10.1074/jbc.M003633200
  5. Mizushima N, Yamamoto A, Matsui M, Yoshimori T and Ohsumi Y (2004) In vivo analysis of autophagy in response to nutrient starvation using transgenic mice expressing a fluorescent autophagosome marker. Mol Biol Cell 15, 1101-1111 https://doi.org/10.1091/mbc.e03-09-0704
  6. Lecker SH, Jagoe RT, Gilbert A et al (2004) Multiple types of skeletal muscle atrophy involve a common program of changes in gene expression. FASEB J 18, 39-51 https://doi.org/10.1096/fj.03-0610com
  7. Petrovski G and Das DK (2010) Does autophagy take a front seat in lifespan extension? J Cell Mol Med 14, 2543-2551 https://doi.org/10.1111/j.1582-4934.2010.01196.x
  8. Zhao J, Brault JJ, Schild A et al (2007) FoxO3 coordinately activates protein degradation by the autophagic/lysosomal and proteasomal pathways in atrophying muscle cells. Cell Metab 6, 472-483 https://doi.org/10.1016/j.cmet.2007.11.004
  9. Koren I, Reem E and Kimchi A (2010) DAP1, a novel substrate of mTOR, negatively regulates autophagy. Curr Biol 20, 1093-1098 https://doi.org/10.1016/j.cub.2010.04.041
  10. Shin J, McFarland DC, Strasburg GM and Velleman SG (2013) Function of death-associated protein 1 in proliferation, differentiation, and apoptosis of chicken satellite cells. Muscle Nerve 48, 777-790 https://doi.org/10.1002/mus.23832
  11. Choi AM, Ryter SW and Levine B (2013) Autophagy in human health and disease. N Engl J Med 368, 651-662 https://doi.org/10.1056/NEJMra1205406
  12. Glick D, Barth S and Macleod KF (2010) Autophagy: cellular and molecular mechanisms. J Pathol 221, 3-12 https://doi.org/10.1002/path.2697
  13. Mizushima N, Yoshimori T and Levine B (2010) Methods in mammalian autophagy research. Cell 140, 313-326 https://doi.org/10.1016/j.cell.2010.01.028
  14. Gallagher LE, Williamson LE and Chan EY (2016) Advances in Autophagy Regulatory Mechanisms. Cells 5, 24 https://doi.org/10.3390/cells5020024
  15. Gwinn DM, Shackelford DB, Egan DF et al (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30, 214-226 https://doi.org/10.1016/j.molcel.2008.03.003
  16. Inoki K, Zhu T and Guan KL (2003) TSC2 mediates cellular energy response to control cell growth and survival. Cell 115, 577-590 https://doi.org/10.1016/S0092-8674(03)00929-2
  17. Le Grand F and Rudnicki MA (2007) Skeletal muscle satellite cells and adult myogenesis. Curr Opin Cell Biol 19, 628-633 https://doi.org/10.1016/j.ceb.2007.09.012
  18. Fiacco E, Castagnetti F, Bianconi V et al (2016) Autophagy regulates satellite cell ability to regenerate normal and dystrophic muscles. Cell Death Differ 23, 1839-1849 https://doi.org/10.1038/cdd.2016.70
  19. Tang AH and Rando TA (2014) Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation. EMBO J 33, 2782-2797 https://doi.org/10.15252/embj.201488278
  20. Sin J, Andres AM, Taylor DJ et al (2016) Mitophagy is required for mitochondrial biogenesis and myogenic differentiation of C2C12 myoblasts. Autophagy 12, 369-380 https://doi.org/10.1080/15548627.2015.1115172
  21. Fortini P, Ferretti C, Iorio E et al (2016) The fine tuning of metabolism, autophagy and differentiation during in vitro myogenesis. Cell Death Dis 7, e2168 https://doi.org/10.1038/cddis.2016.50
  22. Sousa-Victor P, Gutarra S, Garcia-Prat L et al (2014) Geriatric muscle stem cells switch reversible quiescence into senescence. Nature 506, 316-321 https://doi.org/10.1038/nature13013
  23. Garcia-Prat L, Martinez-Vicente M, Perdiguero E et al (2016) Autophagy maintains stemness by preventing senescence. Nature 529, 37-42 https://doi.org/10.1038/nature16187
  24. Knuppertz L and Osiewacz HD (2016) Orchestrating the network of molecular pathways affecting aging: Role of nonselective autophagy and mitophagy. Mech Ageing Dev 153, 30-40 https://doi.org/10.1016/j.mad.2016.01.003
  25. Levine B and Kroemer G (2008) Autophagy in the pathogenesis of disease. Cell 132, 27-42 https://doi.org/10.1016/j.cell.2007.12.018
  26. Schwalm C, Jamart C, Benoit N et al (2015) Activation of autophagy in human skeletal muscle is dependent on exercise intensity and AMPK activation. FASEB J 29, 3515-3526 https://doi.org/10.1096/fj.14-267187
  27. Grumati P, Coletto L, Sabatelli P et al (2010) Autophagy is defective in collagen VI muscular dystrophies, and its reactivation rescues myofiber degeneration. Nat Med 16, 1313-1320 https://doi.org/10.1038/nm.2247
  28. Grumati P, Coletto L, Schiavinato A et al (2011) Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI-deficient muscles. Autophagy 7, 1415-1423 https://doi.org/10.4161/auto.7.12.17877
  29. Lo Verso F, Carnio S, Vainshtein A and Sandri M (2014) Autophagy is not required to sustain exercise and PRKAA1/AMPK activity but is important to prevent mitochondrial damage during physical activity. Autophagy 10, 1883-1894 https://doi.org/10.4161/auto.32154
  30. Tam BT, Pei XM, Yu AP et al (2015) Autophagic adaptation is associated with exercise-induced fibre-type shifting in skeletal muscle. Acta physiologica 214, 221-236 https://doi.org/10.1111/apha.12503
  31. Liu X, Niu Y, Yuan H, Huang J and Fu L (2015) AMPK binds to Sestrins and mediates the effect of exercise to increase insulin-sensitivity through autophagy. Metabolism 64, 658-665 https://doi.org/10.1016/j.metabol.2015.01.015
  32. Lira VA, Okutsu M, Zhang M et al (2013) Autophagy is required for exercise training-induced skeletal muscle adaptation and improvement of physical performance. FASEB J 27, 4184-4193 https://doi.org/10.1096/fj.13-228486
  33. Li FH, Li T, Su YM, Ai JY, Duan R and Liu TC (2018) Cardiac basal autophagic activity and increased exercise capacity. J Physiol Sci 68, 729-742 https://doi.org/10.1007/s12576-018-0592-x
  34. Li FH, Li T, Ai JY et al (2018) Beneficial Autophagic Activities, Mitochondrial Function, and Metabolic Phenotype Adaptations Promoted by High-Intensity Interval Training in a Rat Model. Front Physiol 9, 571 https://doi.org/10.3389/fphys.2018.00571
  35. Komatsu M, Waguri S, Koike M et al (2007) Homeostatic levels of p62 control cytoplasmic inclusion body formation in autophagy-deficient mice. Cell 131, 1149-1163 https://doi.org/10.1016/j.cell.2007.10.035
  36. Kwon I, Lee Y, Cosio-Lima LM, Cho JY and Yeom DC (2015) Effects of long-term resistance exercise training on autophagy in rat skeletal muscle of chloroquine-induced sporadic inclusion body myositis. J Exerc Nutrition Biochem 19, 225-234 https://doi.org/10.5717/jenb.2015.15090710
  37. Sebastian D, Sorianello E, Segales J et al (2016) Mfn2 deficiency links age-related sarcopenia and impaired autophagy to activation of an adaptive mitophagy pathway. EMBO J 35, 1677-1693 https://doi.org/10.15252/embj.201593084
  38. Demontis F and Perrimon N (2010) FOXO/4E-BP signaling in Drosophila muscles regulates organism-wide proteostasis during aging. Cell 143, 813-825 https://doi.org/10.1016/j.cell.2010.10.007
  39. Fry CS, Drummond MJ, Glynn EL et al (2011) Aging impairs contraction-induced human skeletal muscle mTORC1 signaling and protein synthesis. Skelet Muscle 1, 11 https://doi.org/10.1186/2044-5040-1-11
  40. Fry CS, Drummond MJ, Glynn EL et al (2013) Skeletal muscle autophagy and protein breakdown following resistance exercise are similar in younger and older adults. J Gerontol A Biol Sci Med Sci 68, 599-607 https://doi.org/10.1093/gerona/gls209
  41. Halling JF, Ringholm S, Olesen J, Prats C and Pilegaard H (2017) Exercise training protects against aging-induced mitochondrial fragmentation in mouse skeletal muscle in a PGC-1alpha dependent manner. Exp Gerontol 96, 1-6 https://doi.org/10.1016/j.exger.2017.05.020
  42. O'Leary MF, Vainshtein A, Iqbal S, Ostojic O and Hood DA (2013) Adaptive plasticity of autophagic proteins to denervation in aging skeletal muscle. Am J Physiol Cell Physiol 304, C422-430 https://doi.org/10.1152/ajpcell.00240.2012
  43. Carnio S, LoVerso F, Baraibar MA et al (2014) Autophagy impairment in muscle induces neuromuscular junction degeneration and precocious aging. Cell Rep 8, 1509-1521 https://doi.org/10.1016/j.celrep.2014.07.061
  44. Russ DW, Krause J, Wills A and Arreguin R (2012) "SR stress" in mixed hindlimb muscles of aging male rats. Biogerontology 13, 547-555 https://doi.org/10.1007/s10522-012-9399-y
  45. Cuervo AM, Bergamini E, Brunk UT, Droge W, Ffrench M and Terman A (2005) Autophagy and aging: the importance of maintaining "clean" cells. Autophagy 1, 131-140 https://doi.org/10.4161/auto.1.3.2017
  46. Fan J, Kou X, Jia S, Yang X, Yang Y and Chen N (2016) Autophagy as a Potential Target for Sarcopenia. J Cell Physiol 231, 1450-1459 https://doi.org/10.1002/jcp.25260
  47. Luo L, Lu AM, Wang Y et al (2013) 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 48, 427-436 https://doi.org/10.1016/j.exger.2013.02.009
  48. Kim YA, Kim YS, Oh SL, Kim HJ and Song W (2013) Autophagic response to exercise training in skeletal muscle with age. J Physiol Biochem 69, 697-705 https://doi.org/10.1007/s13105-013-0246-7
  49. White Z, Terrill J, White RB et al (2016) Voluntary resistance wheel exercise from mid-life prevents sarcopenia and increases markers of mitochondrial function and autophagy in muscles of old male and female C57BL/6J mice. Skelet Muscle 6, 45 https://doi.org/10.1186/s13395-016-0117-3
  50. Fan J, Yang X, Li J et al (2017) Spermidine coupled with exercise rescues skeletal muscle atrophy from D-gal-induced aging rats through enhanced autophagy and reduced apoptosis via AMPK-FOXO3a signal pathway. Oncotarget 8, 17475-17490 https://doi.org/10.18632/oncotarget.15728
  51. Lenhare L, Crisol BM, Silva VRR et al (2017) Physical exercise increases Sestrin 2 protein levels and induces autophagy in the skeletal muscle of old mice. Exp Gerontol 97, 17-21 https://doi.org/10.1016/j.exger.2017.07.009
  52. Milan G, Romanello V, Pescatore F et al (2015) Regulation of autophagy and the ubiquitin-proteasome system by the FoxO transcriptional network during muscle atrophy. Nat Commun 6, 6670 https://doi.org/10.1038/ncomms7670
  53. Vainshtein A and Hood DA (2016) The regulation of autophagy during exercise in skeletal muscle. J Appl Physiol (1985) 120, 664-673 https://doi.org/10.1152/japplphysiol.00550.2015
  54. Dalle Pezze P, Ruf S, Sonntag AG et al (2016) A systems study reveals concurrent activation of AMPK and mTOR by amino acids. Nat Commun 7, 13254 https://doi.org/10.1038/ncomms13254