The conserved histone chaperone LIN-53 is required for normal lifespan and maintenance of muscle integrity in Caenorhabditis elegans.
Caenorhabditis elegans
aging
chromatin
epigenetics
healthspan
metabolome
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
12 2019
12 2019
Historique:
received:
09
05
2019
revised:
27
06
2019
accepted:
02
07
2019
pubmed:
10
8
2019
medline:
15
9
2020
entrez:
10
8
2019
Statut:
ppublish
Résumé
Whether extension of lifespan provides an extended time without health deteriorations is an important issue for human aging. However, to which degree lifespan and aspects of healthspan regulation might be linked is not well understood. Chromatin factors could be involved in linking both aging aspects, as epigenetic mechanisms bridge regulation of different biological processes. The epigenetic factor LIN-53 (RBBP4/7) associates with different chromatin-regulating complexes to safeguard cell identities in Caenorhabditis elegans as well as mammals, and has a role in preventing memory loss and premature aging in humans. We show that LIN-53 interacts with the nucleosome remodeling and deacetylase (NuRD) complex in C. elegans muscles to ensure functional muscles during postembryonic development and in adults. While mutants for other NuRD members show a normal lifespan, animals lacking LIN-53 die early because LIN-53 depletion affects also the histone deacetylase complex Sin3, which is required for a normal lifespan. To determine why lin-53 and sin-3 mutants die early, we performed transcriptome and metabolomic analysis revealing that levels of the disaccharide trehalose are significantly decreased in both mutants. As trehalose is required for normal lifespan in C. elegans, lin-53 and sin-3 mutants could be rescued by either feeding with trehalose or increasing trehalose levels via the insulin/IGF1 signaling pathway. Overall, our findings suggest that LIN-53 is required for maintaining lifespan and muscle integrity through discrete chromatin regulatory mechanisms. Since both LIN-53 and its mammalian homologs safeguard cell identities, it is conceivable that its implication in lifespan regulation is also evolutionarily conserved.
Identifiants
pubmed: 31397537
doi: 10.1111/acel.13012
pmc: PMC6826145
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
LIN-53 protein, C elegans
0
Repressor Proteins
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13012Subventions
Organisme : ERC
ID : ERC-StG-2014-637530
Pays : International
Organisme : ERC
ID : ERC CIG PCIG12-GA-2012-333922
Pays : International
Organisme : Max Delbrueck Center for Molecular Medicine in the Heon
Pays : International
Informations de copyright
© 2019 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.
Références
Front Public Health. 2017 Dec 11;5:335
pubmed: 29312916
Cell Metab. 2017 Sep 5;26(3):460-474
pubmed: 28826795
Genes Dev. 1998 Aug 15;12(16):2488-98
pubmed: 9716402
Genetics. 2019 Jan;211(1):121-139
pubmed: 30425042
Nat Protoc. 2008;3(6):1101-8
pubmed: 18546601
Exp Gerontol. 2017 Aug;94:29-33
pubmed: 27986499
Trends Endocrinol Metab. 2014 Mar;25(3):138-45
pubmed: 24388149
Front Bioeng Biotechnol. 2015 Jan 21;2:84
pubmed: 25654076
Nat Methods. 2017 Apr;14(4):417-419
pubmed: 28263959
Nature. 2003 Jul 17;424(6946):277-83
pubmed: 12845331
Curr Biol. 2001 Feb 6;11(3):171-6
pubmed: 11231151
Trends Cell Biol. 2009 Jun;19(6):286-94
pubmed: 19394225
Elife. 2016 Apr 19;5:
pubmed: 27090086
Cell. 1998 Dec 23;95(7):981-91
pubmed: 9875852
Proc Natl Acad Sci U S A. 2018 Mar 20;115(12):E2791-E2800
pubmed: 29511104
Nat Med. 2015 Dec;21(12):1416-23
pubmed: 26646498
Mech Ageing Dev. 2019 Jan;177:4-21
pubmed: 30134144
Dev Dyn. 2010 May;239(5):1405-12
pubmed: 20140911
Trends Biochem Sci. 2016 Aug;41(8):700-711
pubmed: 27283514
Proc Natl Acad Sci U S A. 2015 Jan 20;112(3):E277-86
pubmed: 25561524
Genome Biol. 2014;15(12):550
pubmed: 25516281
Nature. 2010 Jul 15;466(7304):383-7
pubmed: 20555324
Curr Top Dev Biol. 2018;127:1-21
pubmed: 29433733
Biochim Biophys Acta. 2004 Mar 15;1677(1-3):3-11
pubmed: 15020040
Nature. 2011 Jan 20;469(7330):343-9
pubmed: 21248841
Curr Opin Cell Biol. 2017 Apr;45:1-7
pubmed: 28129586
Philos Trans R Soc Lond B Biol Sci. 2011 Jan 12;366(1561):9-16
pubmed: 21115525
Cell Mol Life Sci. 2013 Oct;70(19):3513-24
pubmed: 23340908
Gigascience. 2018 Dec 1;7(12):
pubmed: 30277498
Nature. 2012 Mar 04;483(7391):598-602
pubmed: 22388813
Nat Biotechnol. 2008 Dec;26(12):1367-72
pubmed: 19029910
Elife. 2017 Oct 24;6:
pubmed: 29063832
Nature. 2015 Dec 10;528(7581):218-24
pubmed: 26659182
Curr Opin Genet Dev. 2017 Oct;46:83-94
pubmed: 28692904
Aging Cell. 2010 Aug;9(4):558-69
pubmed: 20477758
Int J Parasitol. 2003 Sep 30;33(11):1195-206
pubmed: 13678635
Nat Cell Biol. 2009 Oct;11(10):1261-7
pubmed: 19734887
Aging Cell. 2019 Dec;18(6):e13012
pubmed: 31397537
Nat Genet. 2001 Jun;28(2):139-45
pubmed: 11381260
Bioinformatics. 2005 Apr 15;21(8):1635-8
pubmed: 15613389
Nature. 1996 Aug 8;382(6591):536-9
pubmed: 8700226
Genome Biol. 2008;9(9):R137
pubmed: 18798982
Oncotarget. 2016 Aug 30;7(35):56147-56152
pubmed: 27528229
PLoS Biol. 2007 Aug;5(8):e201
pubmed: 17676974
Nat Methods. 2012 Mar 04;9(4):357-9
pubmed: 22388286
Nat Rev Mol Cell Biol. 2012 Mar 07;13(4):225-238
pubmed: 22395773
Proc Natl Acad Sci U S A. 2006 Nov 7;103(45):16782-7
pubmed: 17075059
Dev Cell. 2018 Sep 10;46(5):611-626.e12
pubmed: 30078731
Nucleic Acids Res. 1998 Apr 1;26(7):1621-7
pubmed: 9512531
J Biol Chem. 2002 Dec 20;277(51):49591-7
pubmed: 12393910
J Biol Chem. 2015 Dec 4;290(49):29375-88
pubmed: 26491019
Cell Mol Life Sci. 2008 Feb;65(3):414-44
pubmed: 17955179
Science. 2018 Sep 28;361(6409):1332-1336
pubmed: 30262494
Nat Genet. 2000 Feb;24(2):180-3
pubmed: 10655066
Cell. 2006 Jun 16;125(6):1165-77
pubmed: 16777605
Sci Transl Med. 2013 Aug 28;5(200):200ra115
pubmed: 23986399
Aging Cell. 2013 Dec;12(6):1012-20
pubmed: 23815345
Aging Cell. 2003 Apr;2(2):111-21
pubmed: 12882324
Nat Cell Biol. 2015 Dec;17(12):1523-35
pubmed: 26571212
Nature. 2010 Jul 22;466(7305):498-502
pubmed: 20613724
Curr Opin Genet Dev. 2017 Oct;46:44-49
pubmed: 28662447
Nature. 2001 Mar 8;410(6825):227-30
pubmed: 11242085
Aging (Albany NY). 2014 Aug;6(8):645-60
pubmed: 25133314
Mol Cell Biol. 1996 Aug;16(8):4349-56
pubmed: 8754835
Cell Mol Biol Lett. 2011 Mar;16(1):114-48
pubmed: 21225470
Nature. 2002 Oct 24;419(6909):808-14
pubmed: 12397350
Nat Biotechnol. 2014 Sep;32(9):896-902
pubmed: 25150836
Nat Rev Mol Cell Biol. 2017 Mar;18(3):141-158
pubmed: 28053344
Cancer Metab. 2014 Jun 30;2:9
pubmed: 25035808
Science. 2011 Jan 21;331(6015):304-8
pubmed: 21148348
Cell. 1996 Oct 4;87(1):95-104
pubmed: 8858152
J Biol Chem. 2000 Mar 31;275(13):9797-804
pubmed: 10734134
Free Radic Biol Med. 2003 Jun 1;34(11):1405-15
pubmed: 12757851
Elife. 2016 Sep 07;5:
pubmed: 27602485