DOI QR코드

DOI QR Code

노화에 따른 골격근에서 운동훈련에 의한 자식작용 반응

The Autophagic Response to Exercise Training of the Skeletal Muscle Fibers in Young and Old Mice

  • 김용안 (충남대학교 생물공학연구소) ;
  • 김영상 (충남대학교 생화학과)
  • Kim, Yong-An (Intitute of Biotechnology, Chungnam Nat'l Univertisy) ;
  • Kim, Young-Sang (Department of Biochemistry, College of Natural Sciences, Chungnam Nat'l University)
  • 투고 : 2010.11.20
  • 심사 : 2011.02.28
  • 발행 : 2011.03.30

초록

Autophagy는 항상성 유지와 스트레스반응을 효율적으로 조정하기 위해 필수적인 세포 내 질적 조절작용이다. 노화가 진행되는 동안 autopahgy에 의한 degradation 효율성 저하와 그로 인한 세포 내 부산물의 축적이 증가하여 결국, 근육의 약화를 초래한다. 그러므로 본 연구의 목적은 골격근에서 운동에 의한 autopahgy 관련 단백질의 변화를 규명하는데 있다. 이를 위해 24마리의 Young 그룹과 Old 그룹을 나누어 각각 대조군(n=6)과 운동군(n=6)으로 배정하였다. 운동은 8주간 주 5회 실시하였고, 트레드밀 속도 16.4 m/min와 경사도 4%로 설정하여 40분간 지속적인 운동을 실시하였다. autopahgy 관련 단백질에 대한 검증 결과 Young 그룹과 비교하여 Old 그룹에서 LC3-1, Beclin-1, Atg7은 모두 유의하게 감소하였다. 그러나 8주간의 규칙적인 운동에 의하여 autophagy 관련 단백질은 증가하는 것으로 나타났다. 따라서 노화에 의해 약화된 autopahgy 기능은 규칙적인 운동에 의해 개선될 수 있을 것으로 사료된다.

Autophagy, a highly conserved mechanism of internal quality control, 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, the aim of this study is to investigate the effects of exercise on autophagic response in skeletal muscle. Twenty-four Young (4 month) and Old (12 month) ICR-type white male mice were divided into a control group (CON: n=6) and exercise training group (Tr: n=6) after an adaptation period of 1 week. Exercise consisted of treadmill running at 16.4 m/min with a 4% incline, 40 min/day and 5 days/week for 8 weeks. Cervical dislocation was performed at 48 hours after the last round of exercise, after which the gastrocnemius skeletal muscle were immediately collected. The results of verifying autophagy formation showed that the Sarcopenia index was decreased in the Old mice compared to the Young. However, it increased with exercise training in the Old. Lipidation LC3-II, Becline-1, and Atg7 were decreased in the Old mice compared to the Young. However, Lipidation LC3-II was significantly increased in the trained Old mice (Young:1 Vs Old:$1.32{\pm}0.042$, p<0.05). Based on these data, we suggest that autophagy regulatory events are the attenuated in Old mice, but that they are enhanced with exercise training.

키워드

참고문헌

  1. Barth, S., D. Glick, and K. F. Macleod. 2010. Autophagy: assays and artifacts. J. Pathol. 221, 117-124. https://doi.org/10.1002/path.2694
  2. Chen, Y., M. B. Azad, and S. B. Gibson. 2010. Methods for detecting autophagy and determining autophagy-induced cell death. Can. J. Physiol. Pharmacol. 88, 285-295. https://doi.org/10.1139/Y10-010
  3. Cuervo, A. M. 2008. Autophagy and aging: keeping that old broom working. Trends Genet. 24, 604-612. https://doi.org/10.1016/j.tig.2008.10.002
  4. Eskelinen, E. L. and P. Saftig. 2009. Autophagy: a lysosomal degradation pathway with a central role in health and disease. Biochim. Biophys. Acta 1793, 664-673. https://doi.org/10.1016/j.bbamcr.2008.07.014
  5. Kim, K. B., Y. A. Kim, and J. J. Park. 2010. Effects of 8 week exercise on bcl-2, bax, caspase-8, caspase-3 and HSP70 in mouse gastrocnemius muscle. J. Life Sci. 20, 1409-1414. https://doi.org/10.5352/JLS.2010.20.9.1409
  6. Komatsu, M., S. Waguri, T. Chiba, S. Murata, J. Iwata, I. Tanida, T. Ueno, M. Koike, Y. Uchiyama, E. Kominami, and K. Tanaka. 2006. Loss of autophagy in the central nervous system causes neurodegeneration in mice. Nature 441, 880-884. https://doi.org/10.1038/nature04723
  7. Maiuri, M. C., E. Zalckvar, A. Kimchi, and G. Kroemer. 2007. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat. Rev. Mol. Cell Biol. 8, 741-752. https://doi.org/10.1038/nrm2239
  8. Masiero, E., L. Agatea, C. Mammucari, B. Blaauw, E. Loro, M. Komatsu, D. Metzger, C. Reggiani, and S. Schiaffino, and M. Sandri. 2009. Autophagy is required to maintain muscle mass. Cell Metab. 10, 507-515. https://doi.org/10.1016/j.cmet.2009.10.008
  9. McMullen, C. A., A. L. Ferry, J. L. Gamboa, F. H. Andrade, and E. E. Dupont-Versteegden. 2009. Age-related changes of cell death pathways in rat extraocular muscle. Exp. Gerontol. 44, 420-425. https://doi.org/10.1016/j.exger.2009.03.006
  10. Mizushima, N. 2007. Autophagy: process and function. Genes Dev. 21, 2861-2873. https://doi.org/10.1101/gad.1599207
  11. Mizushima, N. 2009. Physiological functions of autophagy. Curr. Top Microbiol. Immunol. 335, 71-84. https://doi.org/10.1007/978-3-642-00302-8_3
  12. Mizushima, N., A. Yamamoto, M. Matsui, T. Yoshimori, and Y. Ohsumi. 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.
  13. Mortimore, G. E., N. J. Hutson, and C. A. Surmacz. 1983. Quantitative correlation between proteolysis and macroand microautophagy in mouse hepatocytes during starvation and refeeding. Proc. Natl. Acad. Sci. USA 80, 2179-2183 https://doi.org/10.1073/pnas.80.8.2179
  14. Rajawat, Y. S., Z. Hilioti, and I. Bossis. 2009. Aging: central role for autophagy and the lysosomal degradative system. Ageing Res. Rev. 8,199-213. https://doi.org/10.1016/j.arr.2009.05.001
  15. Salminen, A. and K. Kaarniranta. 2009. Regulation of the aging process by autophagy. Trends Mol. Med. 15, 217-224 https://doi.org/10.1016/j.molmed.2009.03.004
  16. Salminen, A. and K. Kaarniranta. 2009. SIRT1: regulation of longevity via autophagy. Cell Signal. 21, 1356-1360. https://doi.org/10.1016/j.cellsig.2009.02.014
  17. Sandri, M. 2009. Autophagy in skeletal muscle. FEBS Lett. 584, 1411-1416.
  18. Wohlgemuth, S. E., D. Julian, D. E Akin, J. Fried, K. Toscano, C. Leeuwenburgh, and W. A. Dunn. 2007. Autophagy in the heart and liver during normal aging and calorie restriction. Rejuvenation Res. 10, 281-292. https://doi.org/10.1089/rej.2006.0535
  19. Wohlgemuth, S. E, A. Y. Seo, E. Marzetti, H. A. Lees, and C. Leeuwenburgh. 2010. Skeletal muscle autophagy and apoptosis during aging: effects of calorie restriction and life-long exercise. Exp. Gerontol. 45, 138-148. https://doi.org/10.1016/j.exger.2009.11.002
  20. Yen, W. L. and D. J. Klionsky. 2008. How to live long and prosper: autophagy, mitochondria, and aging. Physiology 23, 248-262. https://doi.org/10.1152/physiol.00013.2008