Tinjauan Pustaka : Autophagy dan Sarkopenia

Yuni Susanti Pratiwi; Ronny Lesmana; Setiawan Setiawan; Ambrosius Purba

doi:10.32502/sm.v10i1.1781

Tinjauan Pustaka : Autophagy dan Sarkopenia

Yuni Susanti Pratiwi, Ronny Lesmana, Setiawan Setiawan, Ambrosius Purba

Abstract

ABSTRAK

Sarkopenia adalah penurunan massa dan fungsi otot rangka yang disebabkan oleh penuaan. Sarkopenia dapat meningkatkan morbiditas dan mortalitas pada lansia. Penyebab dan patofisiologi sarkopenia bersifat kompleks dan belum diketahui secara pasti hingga saat ini. Autophagy diketahui mempunyai peran penting untuk proses eliminasi dan daur ulang protein dan organel yang rusak sehingga sementara pada penuaan proses akumulasi berlebihan organel dan protein yang rusak sebagai konsekuensi metabolisme merupakan salah satu penyebab terjadinya penyakit karena penuaan. Kondisi autophagy basal yang baik mempunyai efek protektif terhadap pemeliharaan massa otot dan stimulasi sel satelit untuk proses regenerasi otot. Sementara di sisi lain, inhibisi autophagy menyebabkan penurunan massa otot dan berhubungan dengan atrofi serat otot pada proses penuaan. Inhibisi autophagy diperlukan di awal fase regenerasi myogenesis otot sarkopenia, namun kemudian diduga melalui peran FoXO,autophagy diaktivasi untuk mengeliminasi sel yang rusak dan biogenesis mitokondria. Keseimbangan dinamis dari autophagy merupakan salah satu faktor kunci peranautophagy yang berperan positif pada pencegahan sarkopenia dan bahkan prosesmyogenesis sebagai tatalaksana sarkopenia.

Keywords

autophagy; sarkopenia; penuaan

Full Text:

PDF (Bahasa Indonesia)

References

BPS. Lanjut usia 2017. Statistik Penduduk Lanjut Usia 2017. Jakarta Indonesia; 2017.

Sumantri S, Setiati S, Purnamasari D, Dewiasty E. Relationship between Metformin and Frailty Syndrome in Elderly People with Type 2 Diabetes. 2013;18:183–8.

Ali S, Garcia JM. Sarcopenia, cachexia and aging: Diagnosis, mechanisms and therapeutic options - A mini-review. Gerontology. 2014;60(4):294–305.

Morley J. Sarcopenia in the elderly patient. Eur J Phys Rehabil Med. 2013;49(1):131–43.

Grounds MD. Therapies for sarcopenia and regeneration of old skeletal muscles Support for Excellent In Vivo Capacity of Myogenic Precursor Cells from Old Muscles. BioArchitecture. 2014;4(3):81-87

Viña J, Gomez-Cabrera MC, Borras C, Froio T, Sanchis-Gomar F, Martinez-Bello VE, et al. Mitochondrial biogenesis in exercise and in ageing. Adv Drug Deliv Rev. 2009 Nov 30;61(14):1369–74.

Sartori R, Milan G, Patron M, Mammucari C, Blaauw B, Abraham R, et al. Smad2 and 3 transcription factors control muscle mass in adulthood. Am J Physiol Physiol. 2009 Jun 1;296(6):C1248–57.

Lapierre LR, Kumsta C, Sandri M, Ballabio A. Autophagy Transcriptional and Epigenetic Regulation of Autophagy in Aging. 2015;(April):37–41.

López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217

Barberi L, Scicchitano BM, De Rossi M, Bigot A, Duguez S, Wielgosik A, et al. Age-dependent alteration in muscle regeneration: the critical role of tissue niche. Biogerontology. 2013 Jun;14(3):273–92.

White TA, Lebrasseur K. Myostatin and Sarcopenia : Opportunities and Challenges – A Mini-Review. 2014;55905:289–93.

Miljkovic N, Lim J-Y, Miljkovic I, Frontera WR. Aging of Skeletal Muscle Fibers. Ann Rehabil Med. 2015;39(2):155.

Merlini L, Bonaldo P, Marzetti E. Editorial to “pathophysiological mechanisms of sarcopenia in aging and in muscular dystrophy: A translational approach.” Front Aging Neurosci. 2015;7(JUL):1–6.

Jackson MJ. Age-related loss of skeletal muscle mass and function: The role of dysregulation of redox homeostasis. IUBMB Life. 2009;61(3).

Keller K, Engelhardt M. Strength and muscle mass loss with aging process. Age and strength loss. Muscles Ligaments Tendons J. 2013;3(4):346–50.

Sakuma K, Aoi W, Yamaguchi A. Current understanding of sarcopenia: possible candidates modulating muscle mass. Pflugers Arch Eur J Physiol. 2014;467(2):213–29.

Eriksen CS, Garde E, Reislev NL, Wimmelmann CL, Bieler T, Ziegler AK, et al. Physical activity as intervention for age-related loss of muscle mass and function: protocol for a randomised controlled trial (the LISA study). BMJ Open. 2016;6(12):e012951.

Kim YC, Guan KL. MTOR: A pharmacologic target for autophagy regulation. J Clin Invest. 2015;125(1):25–32.

Marzetti E, Calvani R, Cesari M, Buford TW, Lorenzi M, Behnke BJ, et al. Mitochondrial dysfunction and sarcopenia of aging: From signaling pathways to clinical trials. Int J Biochem Cell Biol. 2013 Oct;45(10):2288–301.

Wohlgemuth SE, Seo AY, Marzetti E, Lees HA, Leeuwenburgh C. Skeletal muscle autophagy and apoptosis during aging: Effects of calorie restriction and life-long exercise. Exp Gerontol. 2010 Feb;45(2):138–48.

Bonaldo P, Sandri M. Cellular and molecular mechanisms of muscle atrophy. Dis Model Mech. 2013;6(1):25–39.

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.

Leduc-Gaudet J-P, Picard M, Pelletier FS-J, Sgarioto N, Auger M-J, Vallée J, et al. Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice. Oncotarget. 2015;6(20):17923–37.

Li L, Tan J, Miao Y, Lei P, Zhang Q. ROS and Autophagy: Interactions and Molecular Regulatory Mechanisms. Cell Mol Neurobiol. 2015 Jul;35(5):615–21.

Rubinsztein DC, Mariño G, Kroemer G. Autophagy and aging. Cell. 2011;146(5):682–95.

Manini TM, Clark BC. Dynapenia and aging: An update. Journals Gerontol - Ser A Biol Sci Med Sci. 2012;67 A(1):28–40.

Fortini P, Iorio E, Dogliotti E, Isidoro C. Coordinated metabolic changes and modulation of autophagy during myogenesis. Front Physiol. 2016;7(JUN):1–4.

Mammucari C, Schiaffino S, Sandri M. Downstream of Akt: FoxO3 and mTOR in the regulation of autophagy in skeletal muscle. Autophagy. 2008;4(4):524–6.

Fritzen AM, Frosig C, Jeppesen J, Jensen TE, Lundsgaard A-M, Serup AK, et al. Role of AMPK in regulation of LC3 lipidation as a marker of autophagy in skeletal muscle. Cell Signal. 2016 Jun;28(6):663–74.

Nguyen PH, Le TVT, Kang HW, Chae J, Kim SK, Kwon K i. I, et al. AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect. Bioorganic Med Chem Lett. 2010;20(14):4128–31.

Masiero E, Agatea L, Mammucari C, Blaauw B, Loro E, Komatsu M, et al. Autophagy is required to maintain muscle mass. Cell Metab. 2009 Dec;10(6):507–15.

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.

Wang L, Waltenberger B, Pferschy-Wenzig EM, Blunder M, Liu X, Malainer C, et al. Natural product agonists of peroxisome proliferator-activated receptor gamma (PPAR?): A review. Biochem Pharmacol. 2014;92(1):73–89.

Boyle AJ, Shih H, Hwang J, Ye J, Lee B, Zhang Y, et al. Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy. Exp Gerontol. 2011 Jul;46(7):549–59.

Zhou J, Chong SY, Lim A, Singh BK, Sinha RA, Salmon AB, et al. Changes in macroautophagy, chaperone-mediated autophagy, and mitochondrial metabolism in murine skeletal and cardiac muscle during aging. Aging (Albany NY). 2017 Feb;9(2):583–99.

Piccirillo R, Demontis F, Perrimon N, Goldberg AL. Mechanisms of muscle growth and atrophy in mammals and Drosophila. Dev Dyn. 2014;243(2):201–15.

Goodpaster BH, Study for the HABC, Park SW, Study for the HABC, Harris TB, Study for the HABC, et al. The Loss of Skeletal Muscle Strength, Mass, and Quality in Older Adults: The Health, Aging and Body Composition Study. Journals Gerontol Ser A. 2006 Oct 1;61(10):1059–64.

Demontis F, Piccirillo R, Goldberg AL, Perrimon N. Mechanisms of skeletal muscle aging: insights from Drosophila and mammalian models. Dis Model Mech. 2013;6(6):1339–52.

Mizushima N, Komatsu M. Autophagy: Renovation of Cells and Tissues. Cell. 2011 Nov 11;147(4):728–41.

Okamoto K. Organellophagy: Eliminating cellular building blocks via selective autophagy. J Cell Biol. 2014;205(4):435–45.

Schiaffino S, Dyar KA, Ciciliot S, Blaauw B, Sandri M. Mechanisms regulating skeletal muscle growth and atrophy. FEBS J. 2013 Sep;280(17):4294–314.

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 Physiol. 2013;304(5):C422–30.

Sakuma K, Kinoshita M, Ito Y, Aizawa M, Aoi W, Yamaguchi A. p62/SQSTM1 but not LC3 is accumulated in sarcopenic muscle of mice. Vol. 7, Journal of Cachexia, Sarcopenia and Muscle. 2016. p. 204–12.

Raben N, Hill V, Shea L, Takikita S, Baum R, Mizushima N, et al. Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease. Hum Mol Genet. 2008 Dec;17(24):3897–908.

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. 2014 Sep 11;8(5):1509–21.

Castets P, Lin S, Rion N, Di Fulvio S, Romanino K, Guridi M, et al. Sustained Activation of mTORC1 in Skeletal Muscle Inhibits Constitutive and Starvation-Induced Autophagy and Causes a Severe, Late-Onset Myopathy. Cell Metab. 2013;17(5):731–44.

Bujak AL, Crane JD, Lally JS, Ford RJ, Kang SJ, Rebalka IA, et al. AMPK Activation of Muscle Autophagy Prevents Fasting-Induced Hypoglycemia and Myopathy during Aging. Cell Metab. 2015;21(6):883–90.

Ibebunjo C, Chick JM, Kendall T, Eash JK, Li C, Zhang Y, et al. Genomic and Proteomic Profiling Reveals Reduced Mitochondrial Function and Disruption of the Neuromuscular Junction Driving Rat Sarcopenia. Mol Cell Biol. 2013 Jan 15;33(2):194 LP – 212.

Katewa SD, Demontis F, Kolipinski M, Hubbard A, Gill MS, Perrimon N, et al. Intramyocellular Fatty-Acid Metabolism Plays a Critical Role in Mediating Responses to Dietary Restriction in Drosophila melanogaster. Cell Metab. 2012;16(1):97–103.

Rivas DA, McDonald DJ, Rice NP, Haran PH, Dolnikowski GG, Fielding RA. Diminished anabolic signaling response to insulin induced by intramuscular lipid accumulation is associated with inflammation in aging but not obesity. Am J Physiol Regul Integr Comp Physiol. 2016 Apr;310(7):R561-9.

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 Jan 6;529:37.

Tang AH, Rando TA. Induction of autophagy supports the bioenergetic demands of quiescent muscle stem cell activation. EMBO J. 2014 Dec 1;33(23):2782–97.

White Z, Terrill J, White RB, McMahon C, Sheard P, Grounds MD, et al. 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. 2016;6(1):45.

Fortini P, Ferretti C, Iorio E, Cagnin M, Garribba L, Pietraforte D, et al. The fine tuning of metabolism, autophagy and differentiation during in vitro myogenesis. Cell Death Dis. 2016;7(3):1–12.

Rabanal-Ruiz Y, Otten EG, Korolchuk VI. mTORC1 as the main gateway to autophagy. Essays Biochem. 2017;61(6):565–84.

Sandri M. Autophagy in skeletal muscle. FEBS Lett. 2010 Apr;584(7):1411–6.

DOI: https://doi.org/10.32502/sm.v10i1.1781