Skip to main content
Springer Nature Link
Log in

Autophagic response to exercise training in skeletal muscle with age

  • Original Paper
  • Published:
Journal of Physiology and Biochemistry Aims and scope Submit manuscript

Abstract

Autophagy, a highly conserved quality control mechanism, is essential for the maintenance of cellular homeostasis and for the orchestration of an efficient cellular response to stress. During aging, the efficiency of autophagic degradation declines, and intracellular waste products accumulate. Therefore, in this study, we tested the hypothesis that skeletal muscle from old mice would have decreased autophagosome formation when compared to the muscle from young mice. We also examined whether autophagic regulatory events differ between muscle fiber types and in response to exercise in aged male mice. The extensor digitorum longus (EDL) and gastrocnemius muscles were studied in young and old ICR mice. Exercise was performed by allowing the mice to run on a treadmill with a 5° incline at 16.4 m/min for 40 min/day, 5 days/week for 8 weeks after a 1-week adaptation period. Our results indicated that the levels of microtubule-associated protein 1b light chain 3, a marker of autophagosome formation, were lower in both the EDL and the gastrocnemius muscle of old mice compared to those young mice. To identify the factors related to the changes observed, the expression of autophagy regulatory proteins was examined in the EDL and gastrocnemius muscles. Beclin-1, autophagy-related gene 7 (ATG7), and lysosome-associated membrane protein were found to be lower in the EDL and gastrocnemius muscles of old mice compared to those in the young mice, then Beclin-1, ATG7, and muscle-specific RING finger protein-1 upregulated after regular exercise. Moreover, the muscle weight/body weight was significantly increased only in the gastrocnemius muscle of the old trained mice. These data suggest that autophagy regulatory events are attenuated in old skeletal muscle. However, this effect is upregulated when animals are subjected to exercise training.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Canada)

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Attaix D, Baracos VE (2010) MAFbx/Atrogin-1 expression is a poor index of muscle proteolysis. Curr Opin Clin Nutr Metab Care 13:223–224

    Article  PubMed  Google Scholar 

  2. Barth S, Glick D, Macleod KF (2010) Autophagy: assays and artifacts. J Pathol 221:117–124

    Article  PubMed  CAS  Google Scholar 

  3. Cao Y, Klionsky DJ (2007) Physiological functions of Atg6/Beclin 1: a unique autophagy-related protein. Cell Res 17:839–849

    Article  PubMed  CAS  Google Scholar 

  4. Cuervo AM (2008) Autophagy and aging: keeping that old broom working. Trends Genet 24:604–612

    Article  PubMed  CAS  Google Scholar 

  5. Cuervo AM, Dice JF (2000) Regulation of LAMP2a levels in the lysosomal membrane. Traffic 1:570–583

    Article  PubMed  CAS  Google Scholar 

  6. Edstrom E, Altun M, Hagglund M, Ulfhake B (2006) Atrogin-1/MAFbx and MuRF1 are downregulated in aging-related loss of skeletal muscle. J Gerontol A Biol Sci Med Sci 61:663–674

    Article  PubMed  Google Scholar 

  7. Eskelinen EL, Saftig P (2009) Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim Biophys Acta 1793:664–673

    Article  PubMed  CAS  Google Scholar 

  8. Glass DJ (2005) Skeletal muscle hypertrophy and atrophy signaling pathways. Int J Biochem Cell Biol 37:1974–1984

    Article  PubMed  CAS  Google Scholar 

  9. He C, Bassik MC, Moresi V, Sun K, Wei Y, Zou Z, An Z, Loh J, Fisher J, Sun Q, Korsmeyer S, Packer M, May HI, Hill JA, Virgin HW, Gilpin C, Xiao G, Bassel-Duby R, Scherer PE, Levine B (2012) Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis. Nature 481:511–515

    Article  PubMed  CAS  Google Scholar 

  10. Kim YA, Kim YS, Song W (2012) Autophagic response to a single bout of moderate exercise in murine skeletal muscle. J Physiol Biochem 68:229–235

    Article  PubMed  CAS  Google Scholar 

  11. Koyama S, Hata S, Witt CC, Ono Y, Lerche S, Ojima K, Chiba T, Doi N, Kitamura F, Tanaka K, Abe K, Witt SH, Rybin V, Gasch A, Franz T, Labeit S, Sorimachi H (2008) Muscle RING-finger protein-1 (MuRF1) as a connector of muscle energy metabolism and protein synthesis. J Mol Biol 376:1224–1236

    Article  PubMed  CAS  Google Scholar 

  12. Leger B, Cartoni R, Praz M, Lamon S, Deriaz O, Crettenand A, Gobelet C, Rohmer P, Konzelmann M, Luthi F, Russell AP (2006) Akt signalling through GSK-3beta, mTOR and Foxo1 is involved in human skeletal muscle hypertrophy and atrophy. J Physiol 576:923–933

    Article  PubMed  CAS  Google Scholar 

  13. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741–752

    Article  PubMed  CAS  Google Scholar 

  14. Marzetti E, Hwang JC, Lees HA, Wohlgemuth SE, Dupont-Versteegden EE, Carter CS, Bernabei R, Leeuwenburgh C (2010) Mitochondrial death effectors: relevance to sarcopenia and disuse muscle atrophy. Biochim Biophys Acta 1800:235–244

    Article  PubMed  CAS  Google Scholar 

  15. Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, Metzger D, Reggiani C, Schiaffino S, Sandri M (2009) Autophagy is required to maintain muscle mass. Cell Metab 10:507–515

    Article  PubMed  CAS  Google Scholar 

  16. Masiero E, Sandri M (2010) Autophagy inhibition induces atrophy and myopathy in adult skeletal muscles. Autophagy 6:307–309

    Article  PubMed  CAS  Google Scholar 

  17. Massey AC, Kaushik S, Sovak G, Kiffin R, Cuervo AM (2006) Consequences of the selective blockage of chaperone-mediated autophagy. Proc Natl Acad Sci USA 103:5805–5810

    Article  PubMed  CAS  Google Scholar 

  18. McElhinny AS, Perry CN, Witt CC, Labeit S, Gregorio CC (2004) Muscle-specific RING finger-2 (MURF-2) is important for microtubule, intermediate filament and sarcomeric M-line maintenance in striated muscle development. J Cell Sci 117:3175–3188

    Article  PubMed  CAS  Google Scholar 

  19. McMullen CA, Ferry AL, Gamboa JL, Andrade FH, Dupont-Versteegden EE (2009) Age-related changes of cell death pathways in rat extraocular muscle. Exp Gerontol 44:420–425

    Article  PubMed  CAS  Google Scholar 

  20. Melendez A, Talloczy Z, Seaman M, Eskelinen EL, Hall DH, Levine B (2003) Autophagy genes are essential for dauer development and life-span extension in C. elegans. Science 301:1387–1391

    Article  PubMed  CAS  Google Scholar 

  21. Mizushima N (2009) Physiological functions of autophagy. Curr Top Microbiol Immunol 335:71–84

    Article  PubMed  CAS  Google Scholar 

  22. Ogata T, Oishi Y, Higuchi M, Muraoka I (2010) Fasting-related autophagic response in slow- and fast-twitch skeletal muscle. Biochem Biophys Res Commun 394:136–140

    Article  PubMed  CAS  Google Scholar 

  23. Rajawat YS, Hilioti Z, Bossis I (2009) Aging: central role for autophagy and the lysosomal degradative system. Ageing Res Rev 8:199–213

    Article  PubMed  CAS  Google Scholar 

  24. Salminen A, Kaarniranta K (2009) Regulation of the aging process by autophagy. Trends Mol Med 15:217–224

    Article  PubMed  CAS  Google Scholar 

  25. Salminen A, Kaarniranta K (2009) SIRT1: regulation of longevity via autophagy. Cell Signal 21:1356–1360

    Article  PubMed  CAS  Google Scholar 

  26. Sandri M (2008) Signaling in muscle atrophy and hypertrophy. Physiology (Bethesda) 23:160–170

    Article  CAS  Google Scholar 

  27. Sandri M (2010) Autophagy in health and disease. 3. Involvement of autophagy in muscle atrophy. Am J Physiol Cell Physiol 298:C1291–1297

    Article  PubMed  CAS  Google Scholar 

  28. Sandri M (2010) Autophagy in skeletal muscle. FEBS Lett 584:1411–1416

    Article  PubMed  CAS  Google Scholar 

  29. Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4:176–184

    PubMed  CAS  Google Scholar 

  30. Terman A, Gustafsson B, Brunk UT (2007) Autophagy, organelles and ageing. J Pathol 211:134–143

    Article  PubMed  CAS  Google Scholar 

  31. Toth ML, Sigmond T, Borsos E, Barna J, Erdelyi P, Takacs-Vellai K, Orosz L, Kovacs AL, Csikos G, Sass M, Vellai T (2008) Longevity pathways converge on autophagy genes to regulate life span in Caenorhabditis elegans. Autophagy 4:330–338

    PubMed  CAS  Google Scholar 

  32. Witt CC, Witt SH, Lerche S, Labeit D, Back W, Labeit S (2008) Cooperative control of striated muscle mass and metabolism by MuRF1 and MuRF2. EMBO J 27:350–360

    Article  PubMed  CAS  Google Scholar 

  33. Wohlgemuth SE, Julian D, Akin DE, Fried J, Toscano K, Leeuwenburgh C, Dunn WA Jr (2007) Autophagy in the heart and liver during normal aging and calorie restriction. Rejuvenation Res 10:281–292

    Article  PubMed  CAS  Google Scholar 

  34. Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C (2010) Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp Gerontol 45:138–148

    Article  PubMed  CAS  Google Scholar 

  35. Yen WL, Klionsky DJ (2008) How to live long and prosper: autophagy, mitochondria, and aging. Physiology (Bethesda) 23:248–262

    Article  CAS  Google Scholar 

Download references

Acknowledgments

Our work is supported by the Basic Science Research Program through the National Research Foundation of Korea, which is funded by the Ministry of Education, Science and Technology (2010-0015964) and was also partly supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MEST) (2011-0030133).

Author information

Authors and Affiliations

  1. Institute of Biotechnology, Chungnam National University, Daejeon, Korea

    Yong An Kim

  2. Department of Biochemistry, Chungnam National University, Daejeon, Korea

    Young Sang Kim

  3. Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-742, Korea

    Yong An Kim, Seung Lyul Oh, Hee-Jae Kim & Wook Song

  4. Institute on Aging, Seoul National University, 599 Gwanangno, Gwanak-gu, Seoul, 151-742, Korea

    Wook Song

Authors
  1. Yong An Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Young Sang Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Seung Lyul Oh
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hee-Jae Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Wook Song
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wook Song.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kim, Y.A., Kim, Y.S., Oh, S.L. et al. Autophagic response to exercise training in skeletal muscle with age. J Physiol Biochem 69, 697–705 (2013). https://doi.org/10.1007/s13105-013-0246-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13105-013-0246-7

Keywords

Search

Navigation