The transcription regulator ATF4 is a mediator of skeletal muscle aging.
ATF4
Aging
Protein turnover
Sarcopenia
Skeletal muscle
Skeletal muscle atrophy
Journal
GeroScience
ISSN: 2509-2723
Titre abrégé: Geroscience
Pays: Switzerland
ID NLM: 101686284
Informations de publication
Date de publication:
Aug 2023
Aug 2023
Historique:
received:
30
01
2023
accepted:
10
03
2023
medline:
27
11
2023
pubmed:
5
4
2023
entrez:
4
4
2023
Statut:
ppublish
Résumé
Aging slowly erodes skeletal muscle strength and mass, eventually leading to profound functional deficits and muscle atrophy. The molecular mechanisms of skeletal muscle aging are not well understood. To better understand mechanisms of muscle aging, we investigated the potential role of ATF4, a transcription regulatory protein that can rapidly promote skeletal muscle atrophy in young animals deprived of adequate nutrition or activity. To test the hypothesis that ATF4 may be involved in skeletal muscle aging, we studied fed and active muscle-specific ATF4 knockout mice (ATF4 mKO mice) at 6 months of age, when wild-type mice have achieved peak muscle mass and function, and at 22 months of age, when wild-type mice have begun to manifest age-related muscle atrophy and weakness. We found that 6-month-old ATF4 mKO mice develop normally and are phenotypically indistinguishable from 6-month-old littermate control mice. However, as ATF4 mKO mice become older, they exhibit significant protection from age-related declines in strength, muscle quality, exercise capacity, and muscle mass. Furthermore, ATF4 mKO muscles are protected from some of the transcriptional changes characteristic of normal muscle aging (repression of certain anabolic mRNAs and induction of certain senescence-associated mRNAs), and ATF4 mKO muscles exhibit altered turnover of several proteins with important roles in skeletal muscle structure and metabolism. Collectively, these data suggest ATF4 as an essential mediator of skeletal muscle aging and provide new insight into a degenerative process that impairs the health and quality of life of many older adults.
Identifiants
pubmed: 37014538
doi: 10.1007/s11357-023-00772-y
pii: 10.1007/s11357-023-00772-y
pmc: PMC10071239
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
2525-2543Subventions
Organisme : NIA NIH HHS
ID : R01 AG060637
Pays : United States
Organisme : NIAMS NIH HHS
ID : R01 AR071762
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM139776
Pays : United States
Informations de copyright
© 2023. The Author(s).
Références
J Gerontol A Biol Sci Med Sci. 2018 Apr 17;73(5):561-570
pubmed: 28958078
Mamm Genome. 2006 Jun;17(6):615-28
pubmed: 16783642
J Exp Med. 2008 May 12;205(5):1227-42
pubmed: 18458112
Aging Cell. 2016 Aug;15(4):634-45
pubmed: 27061426
Mol Cell Biol. 2017 Feb 1;37(4):
pubmed: 27920252
Proc Natl Acad Sci U S A. 2021 Apr 27;118(17):
pubmed: 33888578
Mol Cell Proteomics. 2012 Nov;11(11):1468-74
pubmed: 22865922
Physiology (Bethesda). 2019 Jul 1;34(4):232-239
pubmed: 31165685
Mol Cell. 1998 Nov;2(5):559-69
pubmed: 9844629
Clin Exp Pharmacol Physiol. 2019 Aug;46(8):743-751
pubmed: 31063653
Mol Cell Biol. 2017 Feb 15;37(5):
pubmed: 27956698
Elife. 2019 Apr 29;8:
pubmed: 31033440
Mol Endocrinol. 2009 Sep;23(9):1406-14
pubmed: 19541746
Cell. 2013 Aug 29;154(5):971-982
pubmed: 23993091
Circ Res. 2022 Jun 24;131(1):91-105
pubmed: 35574856
Nat Commun. 2022 Feb 18;13(1):967
pubmed: 35181679
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
J Gerontol A Biol Sci Med Sci. 2006 Oct;61(10):1059-64
pubmed: 17077199
Mol Endocrinol. 2010 Apr;24(4):790-9
pubmed: 20197309
Cell Metab. 2008 Mar;7(3):269-76
pubmed: 18316032
Nature. 2009 Jul 16;460(7253):392-5
pubmed: 19587680
Mech Ageing Dev. 2002 Jan;123(2-3):207-13
pubmed: 11718813
Proteomics. 2018 Mar;18(5-6):e1700108
pubmed: 29453826
Nat Cell Biol. 2013 May;15(5):481-90
pubmed: 23624402
Proteomics. 2020 Mar;20(5-6):e1800403
pubmed: 31408259
Pediatr Neurol. 2005 May;32(5):318-24
pubmed: 15866432
Dis Model Mech. 2014 Dec;7(12):1407-15
pubmed: 25288681
Nucleic Acids Res. 2018 Jul 2;46(W1):W537-W544
pubmed: 29790989
Bioinformatics. 2014 Aug 1;30(15):2114-20
pubmed: 24695404
Genome Biol. 2014;15(12):550
pubmed: 25516281
Biochem Biophys Res Commun. 2018 Nov 30;506(3):571-577
pubmed: 30366664
Nucleic Acids Res. 2017 Jul 27;45(13):7997-8013
pubmed: 28541577
Biochem Soc Trans. 2006 Feb;34(Pt 1):7-11
pubmed: 16246168
Ageing Res Rev. 2014 Nov;18:106-11
pubmed: 25283966
J Biol Chem. 2003 Jun 27;278(26):24139-52
pubmed: 12704194
Mol Cell Biol. 2007 Aug;27(16):5871-86
pubmed: 17562854
Aging Cell. 2014 Dec;13(6):1012-8
pubmed: 25156122
Neurotherapeutics. 2018 Oct;15(4):915-927
pubmed: 30397902
Aging Cell. 2019 Jun;18(3):e12943
pubmed: 30924297
J Exp Biol. 2010 Aug 15;213(Pt 16):2713-25
pubmed: 20675540
J Nutr. 2022 Apr 1;152(4):926-938
pubmed: 34958390
Physiol Rev. 2019 Jan 1;99(1):427-511
pubmed: 30427277
J Vis Exp. 2013 Feb 09;(72):
pubmed: 23426237
Function (Oxf). 2021 May 10;2(4):zqab028
pubmed: 34124684
Mol Cell Biol. 2007 Sep;27(18):6497-505
pubmed: 17620412
Int J Mol Sci. 2018 Aug 08;19(8):
pubmed: 30096787
Free Radic Biol Med. 2016 Oct;99:179-188
pubmed: 27519270
Nat Genet. 2003 Jul;34(3):267-73
pubmed: 12808457
J Biol Chem. 2015 Oct 16;290(42):25497-511
pubmed: 26338703
Mol Biol Cell. 2013 Aug;24(15):2477-90
pubmed: 23761072
Cell. 2002 Sep 6;110(5):639-48
pubmed: 12230980
Proc Natl Acad Sci U S A. 2005 Oct 25;102(43):15545-50
pubmed: 16199517
Nat Commun. 2020 Nov 16;11(1):5808
pubmed: 33199701
Nat Commun. 2022 Aug 16;13(1):4827
pubmed: 35974106
Amino Acids. 2011 Jun;41(1):159-71
pubmed: 20361218
Am J Physiol Endocrinol Metab. 2014 Aug 1;307(3):E245-61
pubmed: 24895282
J Mol Endocrinol. 2018 May;60(4):285-297
pubmed: 29555819
Cells. 2021 Nov 02;10(11):
pubmed: 34831205
Bone. 2019 Oct;127:26-36
pubmed: 31128290
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
J Biol Chem. 2004 Apr 2;279(14):13792-9
pubmed: 14742429
Eur J Cancer. 1995;31A(5):760-5
pubmed: 7503906
Elife. 2021 Mar 01;10:
pubmed: 33646118
Elife. 2021 Dec 23;10:
pubmed: 34939929
Cell. 1999 May 28;97(5):543-6
pubmed: 10367882
Physiol Rev. 2011 Oct;91(4):1447-531
pubmed: 22013216
J Biol Chem. 2014 May 23;289(21):14913-24
pubmed: 24719321
Mol Carcinog. 2022 Sep;61(9):851-864
pubmed: 35726553
J Gen Physiol. 2016 Apr;147(4):309-22
pubmed: 27022191
Proc Natl Acad Sci U S A. 2003 Aug 5;100(16):9440-5
pubmed: 12883005
J Biol Chem. 2020 Feb 28;295(9):2787-2803
pubmed: 31953319
FEBS Lett. 2017 Nov;591(21):3682-3691
pubmed: 28975618
J Appl Physiol (1985). 2018 Jan 01;124(1):40-51
pubmed: 28982947
Sci Rep. 2019 Jul 23;9(1):10694
pubmed: 31337785
FASEB J. 2016 Feb;30(2):798-812
pubmed: 26487695
Mamm Genome. 2013 Apr;24(3-4):142-50
pubmed: 23420545
J Biol Chem. 2012 Aug 10;287(33):27290-301
pubmed: 22692209
Int J Mol Sci. 2020 Aug 05;21(16):
pubmed: 32764267
Blood. 2002 Feb 1;99(3):736-45
pubmed: 11806972
Eur J Hum Genet. 2015 Feb;23(2):159-64
pubmed: 24781756
Aging Cell. 2016 Feb;15(1):89-99
pubmed: 26498839
Cell Metab. 2011 Jun 8;13(6):627-38
pubmed: 21641545
Mol Metab. 2021 Nov;53:101309
pubmed: 34303878
Nucleic Acids Res. 2016 Nov 16;44(20):9719-9732
pubmed: 27471030
Nat Commun. 2021 Jan 12;12(1):330
pubmed: 33436614
Endocrinology. 2018 Mar 1;159(3):1339-1351
pubmed: 29370381
Int J Mol Sci. 2020 Oct 18;21(20):
pubmed: 33081022
J Cell Biol. 2017 Jul 3;216(7):2027-2045
pubmed: 28566324
Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):E117-26
pubmed: 26715744
J Proteome Res. 2023 Feb 3;22(2):311-322
pubmed: 36165806
J Appl Physiol (1985). 2019 Oct 1;127(4):1075-1084
pubmed: 31465716
Am J Physiol Endocrinol Metab. 2004 Oct;287(4):E772-80
pubmed: 15187001
PLoS One. 2009;4(3):e4793
pubmed: 19274082
Genome Biol. 2020 Apr 7;21(1):91
pubmed: 32264951
Nat Aging. 2021 Sep;1(9):760-768
pubmed: 35146440
Dis Model Mech. 2013 Nov;6(6):1339-52
pubmed: 24092876