title: Endoplasmic reticulum stress in human skeletal muscle: any contribution to sarcopenia?
abstract: Skeletal muscle is vital to life as it provides the mechanical power for locomotion, posture and breathing. Beyond these vital functions, skeletal muscle also plays an essential role in the regulation of whole body metabolism, e.g., glucose homeostasis. Although progressive loss of muscle mass with age seems unavoidable, it is critical for older people to keep the highest mass as possible. It is clear that the origin of sarcopenia is multifactorial but, in the present review, it was deliberately chosen to evaluate the likely contribution of one specific cellular stress, namely the endoplasmic reticulum (ER) stress. It is proposed that ER stress can: (1) directly impact muscle mass as one fate of prolonged and unresolved ER stress is cell death and; (2) indirectly create a state of anabolic resistance by inhibiting the mammalian target of rapamycin complex 1 (mTORC1) pathway. With age, many of the key components of the unfolded protein response, such as the chaperones and enzymes, display reduced expression and activity resulting in a dysfunctional ER, accelerating the rate of proteins discarded via the ER-associated degradation. In addition, ER stress can block the mTORC1 pathway which is essential in the response to the anabolic stimulus of nutrients and contractile activity thereby participating to the well-known anabolic resistance state in skeletal muscle during ageing. As exercise increases the expression of several chaperones, it could anticipate or restore the loss of unfolded protein response components with age and thereby reduce the level of ER stress. This hypothesis has not been tested yet but it could be a new mechanism behind the beneficial effects of exercise in the elderly not only for the preservation of muscle mass but also for the regulation of whole body metabolism.
authors.affiliation: Exercise Physiology Research Group, Department of Kinesiology, FaBeR, KU Leuven Leuven, Belgium.
authors.forename: Louise
authors.initials: L
authors.lastname: Deldicque
keywords: ATF6; IRE1α; PERK; ageing; anabolic resistance; exercise; unfolded protein response
references.citation: Nature. 2008 Jul 24;454(7203):455-62
references.pmid: 18650916
references.citation: Br Med Bull. 2010;95:139-59
references.pmid: 20200012
references.citation: Cell. 2001 Dec 28;107(7):881-91
references.pmid: 11779464
references.citation: Biochem Biophys Res Commun. 2010 Mar 26;394(1):136-40
references.pmid: 20184860
references.citation: Neoplasia. 2011 Jul;13(7):590-600
references.pmid: 21750653
references.citation: J Physiol. 2008 Dec 15;586(24):6049-61
references.pmid: 18955382
references.citation: Exerc Sport Sci Rev. 2012 Jan;40(1):43-9
references.pmid: 21918459
references.citation: FASEB J. 2007 Dec;21(14):4013-27
references.pmid: 17660348
references.citation: Mol Cancer Ther. 2007 Apr;6(4):1262-75
references.pmid: 17431104
references.citation: Exp Gerontol. 1972 Feb;7(1):53-67
references.pmid: 4402173
references.citation: Mol Cell Biochem. 2009 Aug;328(1-2):217-24
references.pmid: 19370316
references.citation: J Am Geriatr Soc. 2002 May;50(5):889-96
references.pmid: 12028177
references.citation: Appl Physiol Nutr Metab. 2009 Jun;34(3):377-81
references.pmid: 19448702
references.citation: Cell. 2009 Aug 7;138(3):562-75
references.pmid: 19665977
references.citation: J Gerontol A Biol Sci Med Sci. 2006 May;61(5):435-43
references.pmid: 16720739
references.citation: Med Sci Sports Exerc. 2011 Jan;43(1):18-25
references.pmid: 20473228
references.citation: Science. 2006 Jul 7;313(5783):104-7
references.pmid: 16825573
references.citation: J Neurosci. 2008 Jun 25;28(26):6539-48
references.pmid: 18579727
references.citation: Science. 2000 Jan 28;287(5453):664-6
references.pmid: 10650002
references.citation: J Nutr Health Aging. 2005 Nov-Dec;9(6):408-19
references.pmid: 16395513
references.citation: Trends Cell Biol. 2008 May;18(5):228-35
references.pmid: 18346894
references.citation: Methods Enzymol. 2008;442:395-419
references.pmid: 18662581
references.citation: J Neurochem. 2006 Mar;96(5):1491-9
references.pmid: 16441512
references.citation: Acta Neuropathol. 2007 Nov;114(5):527-35
references.pmid: 17661063
references.citation: Nature. 2000 Nov 9;408(6809):239-47
references.pmid: 11089981
references.citation: J Physiol. 2009 Dec 1;587(Pt 23):5753-65
references.pmid: 19822547
references.citation: FASEB J. 2000 May;14(7):847-58
references.pmid: 10783138
references.citation: Semin Cell Dev Biol. 1999 Oct;10(5):465-72
references.pmid: 10597629
references.citation: Am J Physiol Endocrinol Metab. 2006 Apr;290(4):E731-8
references.pmid: 16263770
references.citation: Maturitas. 2012 Feb;71(2):109-14
references.pmid: 22153348
references.citation: Aging Cell. 2007 Oct;6(5):599-606
references.pmid: 17681036
references.citation: Int J Mol Sci. 2010 Apr 12;11(4):1509-26
references.pmid: 20480032
references.citation: Scand J Med Sci Sports. 2010 Feb;20(1):5-9
references.pmid: 19558380
references.citation: Oncogene. 2008 Oct 27;27(50):6419-33
references.pmid: 18955970
references.citation: Cell Mol Life Sci. 2011 Mar;68(6):1021-31
references.pmid: 21116678
references.citation: Biotechnol Bioeng. 2011 Dec;108(12):2777-93
references.pmid: 21809331
references.citation: J Physiol Biochem. 2013 Jun;69(2):215-25
references.pmid: 23011781
references.citation: Eur J Appl Physiol. 2011 Jul;111(7):1553-8
references.pmid: 21188411
references.citation: Front Physiol. 2012 Jul 16;3:263
references.pmid: 22934019
references.citation: Annu Rev Biochem. 2005;74:739-89
references.pmid: 15952902
references.citation: J Virol. 2005 Jun;79(11):6890-9
references.pmid: 15890928
references.citation: Ageing Res Rev. 2009 Jul;8(3):160-72
references.pmid: 19427411
references.citation: Mol Cell Biol. 2006 Apr;26(8):3071-84
references.pmid: 16581782
references.citation: Am J Epidemiol. 1998 Apr 15;147(8):755-63
references.pmid: 9554417
references.citation: Cell Metab. 2011 Feb 2;13(2):160-9
references.pmid: 21284983
references.citation: EMBO J. 1998 Oct 1;17(19):5708-17
references.pmid: 9755171
references.citation: FASEB J. 2004 Oct;18(13):1553-5
references.pmid: 15319364
references.citation: Autophagy. 2009 Nov;5(8):1217-9
references.pmid: 19829057
references.citation: Am J Physiol. 1997 Oct;273(4):E790-800
references.pmid: 9357810
references.citation: Mol Cell. 2012 Nov 9;48(3):353-64
references.pmid: 23022383
references.citation: Biochem Biophys Res Commun. 2007 Apr 6;355(2):365-70
references.pmid: 17300747
references.citation: Trends Endocrinol Metab. 2009 May;20(4):194-201
references.pmid: 19349192
references.citation: Ageing Res Rev. 2009 Jul;8(3):150-9
references.pmid: 19491040
references.citation: Am J Physiol Cell Physiol. 2013 Mar 1;304(5):C422-30
references.pmid: 23220115
references.citation: Am J Clin Nutr. 2009 Nov;90(5):1343-50
references.pmid: 19740975
references.citation: Cell Death Differ. 2011 Jan;18(1):133-44
references.pmid: 20616807
references.citation: J Cereb Blood Flow Metab. 2005 Jun;25(6):694-712
references.pmid: 15716857
references.citation: Neurobiol Aging. 2006 Jul;27(7):973-82
references.pmid: 15964666
references.citation: Science. 2011 Nov 25;334(6059):1081-6
references.pmid: 22116877
references.citation: J Am Soc Nephrol. 2013 Jul;24(8):1223-33
references.pmid: 23723427
references.citation: Chem Biol. 1998 May;5(5):R97-103
references.pmid: 9578633
references.citation: PLoS One. 2011;6(6):e20993
references.pmid: 21698202
references.citation: Mol Cell. 2008 Mar 14;29(5):541-51
references.pmid: 18342602
references.citation: Cell Death Differ. 2006 Mar;13(3):374-84
references.pmid: 16397578
references.citation: Cell Death Dis. 2011 Feb 10;2:e118
references.pmid: 21368889
references.citation: Am J Physiol. 1995 Mar;268(3 Pt 1):E422-7
references.pmid: 7900788
references.citation: Cell Death Dis. 2012 Jun 28;3:e333
references.pmid: 22739985
references.citation: Int J Cell Biol. 2010;2010:930509
references.pmid: 20145727
references.citation: FASEB J. 2005 Mar;19(3):422-4
references.pmid: 15596483
references.citation: Biol Chem. 2010 Jul;391(7):791-801
references.pmid: 20624000
references.citation: J Biol Chem. 2003 May 9;278(19):16726-31
references.pmid: 12609979
references.citation: Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E695-705
references.pmid: 20501874
references.citation: Am J Physiol Endocrinol Metab. 2010 Nov;299(5):E752-63
references.pmid: 20739510
references.citation: Br J Clin Pharmacol. 2013 Mar;75(3):708-15
references.pmid: 22957963
references.citation: Cell Death Differ. 2004 Apr;11(4):381-9
references.pmid: 14685163
references.citation: Am J Physiol Cell Physiol. 2013 Jun 15;304(12):C1117-26
references.pmid: 23515532
references.citation: Am J Respir Cell Mol Biol. 2012 Jun;46(6):748-56
references.pmid: 22227563
references.citation: Apoptosis. 2013 May;18(5):537-46
references.pmid: 23430059
references.citation: JAMA. 2001 Sep 12;286(10):1206-12
references.pmid: 11559266
references.citation: Nat Rev Mol Cell Biol. 2002 Jun;3(6):411-21
references.pmid: 12042763
references.citation: Biochem Biophys Res Commun. 2008 Jan 11;365(2):355-61
references.pmid: 17996725
references.citation: Nat Rev Mol Cell Biol. 2007 Jul;8(7):519-29
references.pmid: 17565364
references.citation: Ageing Res Rev. 2010 Jul;9(3):211-7
references.pmid: 20416402
references.citation: J Cell Biol. 2012 Mar 19;196(6):689-98
references.pmid: 22431749
references.citation: Mech Ageing Dev. 2009 May;130(5):328-36
references.pmid: 19428451
references.citation: Diabetes Nutr Metab. 2000 Apr;13(2):99-107
references.pmid: 10898128
references.citation: Rev Neurosci. 2009;20(1):23-37
references.pmid: 19526732
references.citation: EMBO Rep. 2006 Sep;7(9):880-5
references.pmid: 16953201