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Current Aging Science

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ISSN (Print): 1874-6098
ISSN (Online): 1874-6128

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Review Article

An Overview of Neuromuscular Junction Aging Findings in Human and Animal Studies

Author(s): Shaweta Khosa, Bhavesh Trikamji, Gurveer S. Khosa , Hadi M. Khanli and Shri K. Mishra*

Volume 12, Issue 1, 2019

Page: [28 - 34] Pages: 7

DOI: 10.2174/1874609812666190603165746

Abstract

Background: Aging is a complex irreversible process that is not only related to an individual’s genetic make-up but also to lifestyle choices and environmental exposures. Like every other structure in human body, the Neuromuscular Junction (NMJ) is not averse to aging.

Objectives: The prime objective is to analyse the microscopic and macroscopic changes at the NMJs with aging.

Methods: For the purpose of review we evaluated data from resources like Pubmed, Ovid, UCLA libraries and USC libraries.

Results: We review various morphological, physiological, immunological, and biochemical changes in NMJs with aging and their management.

Conclusion: The alterations in NMJs secondary to aging are inevitable. It is vital that neurologists clearly understand the pathophysiology of NMJ aging and differentiate between physiological and pathological effects of aging. With the current knowledge of science, the changes in NMJ aging can be better prevented rather than cured.

Keywords: Neuromuscular junction, aging, atrophy, neurotransmitter, synapse, oxidative stress, sarcopenia.

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Graphical Abstract

[1]
Mishra SK, Misra V. Muscle sarcopenia: an overview. Acta Myol 2003; 22(2): 43-7.
[2]
Rosenberg IH. Sarcopenia: Origins and clinical relevance. J Nutr 1997; 127(5)(Suppl.): 990S-1S.
[3]
Sanes JR, Lichtman JW. Development of the vertebrate neuromuscular junction. Annu Rev Neurosci 1999; 22: 389-442.
[4]
Kim N, Stiegler AL, Cameron TO, Hallock PT, Gomez AM, Huang JH, et al. Lrp4 is a receptor for Agrin and forms a complex with MuSK. Cell 2008; 135(2): 334-42.
[5]
Okada K, Inoue A, Okada M, et al. The muscle protein Dok-7 is essential for neuromuscular synaptogenesis. Science 2006; 312(5781): 1802-5.
[6]
Misgeld T, Kummer TT, Lichtman JW, Sanes JR. Agrin promotes synaptic differentiation by counteracting an inhibitory effect of neurotransmitter. Proc Natl Acad Sci USA 2005; 102(31): 11088-93.
[7]
Butikofer L, Zurlinden A, Bolliger MF, Kunz B, Sonderegger P. Destabilization of the neuromuscular junction by proteolytic cleavage of agrin results in precocious sarcopenia. FASEB J 2011; 25(12): 4378-93.
[8]
Campanari ML, García-Ayllón MS, Ciura S, Sáez-Valero J, Kabashi E. Neuromuscular junction impairment in amyotrophic lateral sclerosis: Reassessing the role of acetylcholinesterase. Front Mol Neurosci 2016; 9: 160.
[9]
Rosenheimer JL, Smith DO. Differential changes in the end-plate architecture of functionally diverse muscles during aging. J Neurophysiol 1985; 53(6): 1567-81.
[10]
McMullen CA, Andrade FH. Functional and morphological evidence of age-related denervation in rat laryngeal muscles. J Gerontol A Biol Sci Med Sci 2009; 64(4): 435-42.
[11]
Jang YC, Van Remmen H. Age-associated alterations of the neuromuscular junction. Exp Gerontol 2011; 46(2-3): 193-8.
[12]
Rudolf R, Khan MM, Labeit S, Deschenes MR. Degeneration of neuromuscular junction in age and dystrophy. Front Aging Neurosci 2014; 6: 99.
[13]
Taetzsch T, Valdez G. NMJ maintenance and repair in aging. Curr Opin Physiol 2018; 4: 57-64.
[14]
Oki S, Desaki J, Ezaki T, Matsuda Y. Aged neuromuscular junctions in the extensor digitorum longus muscle of the rat as revealed by scanning electron microscopy. J Electron Microsc (Tokyo) 1999; 48(3): 297-300.
[15]
Beramendi A, Peron S, Casanova G, Reggiani C, Cantera R. Neuromuscular junction in abdominal muscles of Drosophila melanogaster during adulthood and aging. J Comp Neurol 2007; 501(4): 498-508.
[16]
Garcia ML, Fernandez A, Solas MT. Mitochondria, motor neurons and aging. J Neurol Sci 2013; 330(1-2): 18-26.
[17]
Fahim MA, Holley JA, Robbins N. Scanning and light microscopic study of age changes at a neuromuscular junction in the mouse. J Neurocytol 1983; 12(1): 13-25.
[18]
Arizono N, Koreto O, Iwai Y, Hidaka T, Takeoka O. Morphometric analysis of human neuromuscular junction in different ages. Acta Pathol Jpn 1984; 34(6): 1243-9.
[19]
Wokke JH, Jennekens FG, van den Oord CJ, Veldman H, Smit LM, Leppink GJ. Morphological changes in the human end plate with age. J Neurol Sci 1990; 95(3): 291-310.
[20]
Smith DO. Restricted diffusion of extracellular potassium at the neuromuscular junction of aged rats. Brain Res 1982; 239(2): 668-73.
[21]
Smith DO, Rosenheimer JL. Factors governing speed of action potential conduction and neuromuscular transmission in aged rats. Exp Neurol 1984; 83(2): 358-66.
[22]
Kazama H, Morimoto-Tanifuji T, Nose A. Postsynaptic activation of calcium/calmodulin-dependent protein kinase II promotes coordinated pre- and postsynaptic maturation of Drosophila neuromuscular junctions. Neuroscience 2003; 117(3): 615-25.
[23]
Kulakowski SA, Parker SD, Personius KE. Reduced TrkB expression results in precocious age-like changes in neuromuscular structure, neurotransmission, and muscle function. J Appl Physiol (1985) 2011;; 111(3): 844-52.
[24]
Salmon AB, Richardson A, Perez VI. Update on the oxidative stress theory of aging: Does oxidative stress play a role in aging or healthy aging? Free Radic Biol Med 2010; 48(5): 642-55.
[25]
Graus YM, Verschuuren JJ, Spaans F, Jennekens F, van Breda VPJ, De Baets MH. Age-related resistance to experimental autoimmune myasthenia gravis in rats. J Immunol 1993; 150(9): 4093-103.
[26]
Gorlewicz A, Wlodarczyk J, Wilczek E, Gawlak M, Cabaj A, Majczynski H, et al. CD44 is expressed in non-myelinating Schwann cells of the adult rat, and may play a role in neurodegeneration-induced glial plasticity at the neuromuscular junction. Neurobiol Dis 2009; 34(2): 245-58.
[27]
McCullough MJ, Peplinski NG, Kinnell KR, Spitsbergen JM. Glial cell line-derived neurotrophic factor protein content in rat skeletal muscle is altered by increased physical activity in vivo and in vitro. Neuroscience 2011; 174: 234-44.
[28]
Messi ML, Delbono O. Target-derived trophic effect on skeletal muscle innervation in senescent mice. J Neurosci 2003; 23(4): 1351-9.
[29]
Drey M, Sieber CC, Bauer JM, Uter W, Dahinden P, Fariello RG, et al. C-terminal Agrin Fragment as a potential marker for sarcopenia caused by degeneration of the neuromuscular junction. Exp Gerontol 2013; 48(1): 76-80.
[30]
Samuel MA, Valdez G, Tapia JC, Lichtman JW, Sanes JR. Agrin and synaptic laminin are required to maintain adult neuromuscular junctions. PLoS One 2012; 7(10)e46663
[31]
Lee KM, Chand KK, Hammond LA, Lavidis NA, Noakes PG. Functional decline at the aging neuromuscular junction is associated with altered laminin-alpha4 expression. Aging (Albany NY) 2017; 9(3): 880-99.
[32]
Stamatakou E, Salinas PC. Postsynaptic assembly: A role for Wnt signaling. Dev Neurobiol 2014; 74(8): 818-27.
[33]
Gouspillou G, Picard M, Godin R, Burelle Y, Hepple RT. Role of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1alpha) in denervation-induced atrophy in aged muscle: Facts and hypotheses. Longev Healthspan 2013; 2(1): 13.
[34]
Franke B, Gasch A, Rodriguez D, Chami M, Khan MM, Rudolf R, et al. Molecular basis for the fold organization and sarcomeric targeting of the muscle atrogin MuRF1. Open Biol 2014; 4130172
[35]
Personius KE, Parker SD. TrkB expression at the neuromuscular junction is reduced during aging. Muscle Nerve 2013; 47(4): 532-8.
[36]
Satoh A, Brace CS, Rensing N, Cliften P, Wozniak DF, Herzog ED, et al. Sirt1 extends life span and delays aging in mice through the regulation of Nk2 homeobox 1 in the DMH and LH. Cell Metab 2013; 18(3): 416-30.
[37]
Snyder-Warwick AK, Satoh A, Santosa KB, Imai SI, Jablonka-Shariff A. Hypothalamic Sirt1 protects terminal Schwann cells and neuromuscular junctions from age-related morphological changes. Aging Cell 2018; 17(4)e12776
[38]
Cheng A, Morsch M, Murata Y, Ghazanfari N, Reddel SW, Phillips WD. Sequence of age-associated changes to the mouse neuromuscular junction and the protective effects of voluntary exercise. PLoS One 2013; 8(7)e67970
[39]
Valdez G, Tapia JC, Kang H, Clemenson GD Jr, Gage FH, Lichtman JW, et al. Attenuation of age-related changes in mouse neuromuscular synapses by caloric restriction and exercise. Proc Natl Acad Sci USA 2010; 107(33): 14863-8.
[40]
Jang YC, Liu Y, Hayworth CR, Bhattacharya A, Lustgarten MS, Muller FL, et al. Dietary restriction attenuates age-associated muscle atrophy by lowering oxidative stress in mice even in complete absence of CuZnSOD. Aging Cell 2012; 11(5): 770-82.
[41]
Wang CY, Yang F, He XP, Je HS, Zhou JZ, Eckermann K, et al. Regulation of neuromuscular synapse development by glial cell line-derived neurotrophic factor and neurturin. J Biol Chem 2002; 277(12): 10614-25.
[42]
Gomez-Pinilla PJ, Camello-Almaraz C, Moreno R, Camello PJ, Pozo MJ. Melatonin treatment reverts age-related changes in Guinea pig gallbladder neuromuscular transmission and contractility. J Pharmacol Exp Ther 2006; 319(2): 847-56.
[43]
Aldunate R, Minniti AN, Rebolledo D, Inestrosa NC. Synaptic defects associated with s-inclusion body myositis are prevented by copper. Biometals 2012; 25(4): 815-24.
[44]
Jang YC, Lustgarten MS, Liu Y, Muller FL, Bhattacharya A, Liang H, et al. Increased superoxide in vivo accelerates age-associated muscle atrophy through mitochondrial dysfunction and neuromuscular junction degeneration. FASEB J 2010; 24(5): 1376-90.

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