Expression of mitochondrial oxidative stress response genes in muscle is associated with mitochondrial respiration, physical performance, and muscle mass in the Study of Muscle, Mobility, and Aging.

Publisher: Wiley-Blackwell Country of Publication: England NLM ID: 101130839 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1474-9726 (Electronic) Linking ISSN: 14749718 NLM ISO Abbreviation: Aging Cell Subsets: MEDLINE

Publication: Oxford, UK : Wiley-Blackwell
Original Publication: Oxford, UK : Blackwell Pub., c2002-

Oxidative Stress*/genetics ; Aging*/genetics ; Aging*/metabolism ; Muscle, Skeletal*/metabolism; Humans ; Aged ; Male ; Female ; Physical Functional Performance ; Mitochondria/metabolism ; Mitochondria/genetics ; Mitochondria, Muscle/metabolism ; Mitochondria, Muscle/genetics ; Aged, 80 and over

Gene expression in skeletal muscle of older individuals may reflect compensatory adaptations in response to oxidative damage that preserve tissue integrity and maintain function. Identifying associations between oxidative stress response gene expression patterns and mitochondrial function, physical performance, and muscle mass in older individuals would further our knowledge of mechanisms related to managing molecular damage that may be targeted to preserve physical resilience. To characterize expression patterns of genes responsible for the oxidative stress response, RNA was extracted and sequenced from skeletal muscle biopsies collected from 575 participants (≥70 years old) from the Study of Muscle, Mobility, and Aging. Expression levels of 21 protein-coding RNAs related to the oxidative stress response were analyzed in relation to six phenotypic measures, including maximal mitochondrial respiration from muscle biopsies (Max OXPHOS), physical performance (VO 2 peak, 400-m walking speed, and leg strength), and muscle size (thigh muscle volume and whole-body D3Cr muscle mass). The mRNA level of the oxidative stress response genes most consistently associated across outcomes are preferentially expressed within the mitochondria. Higher expression of mRNAs that encode generally mitochondria located proteins SOD2, TRX2, PRX3, PRX5, and GRX2 were associated with higher levels of mitochondrial respiration and VO 2 peak. In addition, greater SOD2, PRX3, and GRX2 expression was associated with higher physical performance and muscle size. Identifying specific mechanisms associated with high functioning across multiple performance and physical domains may lead to targeted antioxidant interventions with greater impacts on mobility and independence.
(© 2024 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.)

Update of: medRxiv. 2023 Nov 06:2023.11.05.23298108. doi: 10.1101/2023.11.05.23298108. (PMID: 37986804)

Oxid Med Cell Longev. 2018 Jul 2;2018:7857251. (PMID: 30057684)
Antioxid Redox Signal. 2020 Apr 1;32(10):701-714. (PMID: 31968997)
J Gen Intern Med. 2011 Feb;26(2):130-5. (PMID: 20972641)
FASEB J. 2010 May;24(5):1376-90. (PMID: 20040516)
Nat Biotechnol. 2019 Aug;37(8):907-915. (PMID: 31375807)
Aging Cell. 2024 Jun;23(6):e14114. (PMID: 38831629)
Aging Cell. 2017 Feb;16(1):104-112. (PMID: 27683245)
Med Sci Sports Exerc. 1982;14(5):377-81. (PMID: 7154893)
Proteomes. 2016 May 06;4(2):. (PMID: 28248228)
Med Sci Sports Exerc. 2001 Jul;33(7):1126-41. (PMID: 11445760)
Metabolites. 2021 Jun 28;11(7):. (PMID: 34203260)
Antioxidants (Basel). 2021 Nov 17;10(11):. (PMID: 34829696)
Bioinformatics. 2015 Jan 15;31(2):166-9. (PMID: 25260700)
J Appl Physiol (1985). 2016 Nov 1;121(5):1047-1052. (PMID: 27197856)
Aging Clin Exp Res. 2008 Aug;20(4):302-9. (PMID: 18852542)
Circulation. 2007 Jul 17;116(3):329-43. (PMID: 17576872)
Cell. 2013 Jun 6;153(6):1194-217. (PMID: 23746838)
Physiol Rev. 2008 Oct;88(4):1243-76. (PMID: 18923182)
Redox Biol. 2018 Jul;17:297-314. (PMID: 29775961)
Mol Cell Neurosci. 2019 Mar;95:59-70. (PMID: 30763691)
Cells. 2019 Jul 30;8(8):. (PMID: 31366062)
Genome Biol. 2014;15(12):550. (PMID: 25516281)
JAMA. 2007 May 16;297(19):2081-91. (PMID: 17507344)
J Appl Physiol (1985). 2012 Jun;112(11):1940-8. (PMID: 22422801)
PLoS Genet. 2015 Feb 11;11(2):e1004972. (PMID: 25671321)
Circulation. 2010 Jul 13;122(2):191-225. (PMID: 20585013)
J Gerontol A Biol Sci Med Sci. 2023 Aug 2;78(8):1367-1375. (PMID: 36462195)
Free Radic Biol Med. 2015 Nov;88(Pt B):314-336. (PMID: 26066302)
J Am Geriatr Soc. 2004 Jul;52(7):1105-13. (PMID: 15209648)
Annu Rev Pharmacol Toxicol. 2013;53:401-26. (PMID: 23294312)
JAMA. 2011 Jan 5;305(1):50-8. (PMID: 21205966)
Oncoimmunology. 2013 Apr 1;2(4):e23793. (PMID: 23734326)
Biochem J. 2009 Dec 23;425(2):313-25. (PMID: 20025614)
J Gerontol A Biol Sci Med Sci. 2015 Nov;70(11):1394-9. (PMID: 25030980)
Free Radic Biol Med. 2016 Sep;98:208-217. (PMID: 26912035)
Med Sci Sports Exerc. 1982;14(1):101-2. (PMID: 7070249)
Obesity (Silver Spring). 2018 Nov;26(11):1785-1795. (PMID: 29785727)
Ageing Res Rev. 2021 May;67:101305. (PMID: 33610815)
J Gerontol A Biol Sci Med Sci. 2023 Oct 28;78(11):2083-2093. (PMID: 36754371)
Cell Signal. 2006 Jan;18(1):69-82. (PMID: 15927447)
J Appl Physiol (1985). 2011 Sep;111(3):844-52. (PMID: 21737823)
J Cachexia Sarcopenia Muscle. 2013 Jun 25;:. (PMID: 23797207)
J Proteome Res. 2010 May 7;9(5):2516-26. (PMID: 20377239)
J Biol Chem. 2001 Oct 19;276(42):38388-93. (PMID: 11507097)
Mol Cells. 2011 Dec;32(6):491-509. (PMID: 22207195)
JAMA. 2014 Jun 18;311(23):2387-96. (PMID: 24866862)

R01 AG059416 United States AG NIA NIH HHS; R01AG059416 United States AG NIA NIH HHS; UL10TR001420 National Center for Advancing Translational Science, at Wake Forest University; P30AG021332 United States AG NIA NIH HHS; UL1 TR001420 United States TR NCATS NIH HHS; P30AG024827 United States AG NIA NIH HHS

Keywords: aging; cohort study; gene expression; mitochondria; muscle; oxidative stress

Date Created: 20240604 Date Completed: 20240611 Latest Revision: 20240708

20240709

PMC11166362

10.1111/acel.14114

38831629