Expression of retrotransposons contributes to aging in Drosophila.
412
Retrofind
Roo
aging
lifespan extension
retrotransposon
Journal
Genetics
ISSN: 1943-2631
Titre abrégé: Genetics
Pays: United States
ID NLM: 0374636
Informations de publication
Date de publication:
26 05 2023
26 05 2023
Historique:
received:
12
12
2022
accepted:
11
04
2023
pmc-release:
21
04
2024
medline:
29
5
2023
pubmed:
21
4
2023
entrez:
21
04
2023
Statut:
ppublish
Résumé
Retrotransposons are a class of transposable elements capable of self-replication and insertion into new genomic locations. Across species, the mobilization of retrotransposons in somatic cells has been suggested to contribute to the cell and tissue functional decline that occurs during aging. Retrotransposons are broadly expressed across cell types, and de novo insertions have been observed to correlate with tumorigenesis. However, the extent to which new retrotransposon insertions occur during normal aging and their effect on cellular and animal function remains understudied. Here, we use a single nucleus whole genome sequencing approach in Drosophila to directly test whether transposon insertions increase with age in somatic cells. Analyses of nuclei from thoraces and indirect flight muscles using a newly developed pipeline, Retrofind, revealed no significant increase in the number of transposon insertions with age. Despite this, reducing the expression of two different retrotransposons, 412 and Roo, extended lifespan, but did not alter indicators of health such as stress resistance. This suggests a key role for transposon expression and not insertion in regulating longevity. Transcriptomic analyses revealed similar changes to gene expression in 412 and Roo knockdown flies and highlighted changes to genes involved in proteolysis and immune function as potential contributors to the observed changes in longevity. Combined, our data show a clear link between retrotransposon expression and aging.
Identifiants
pubmed: 37084379
pii: 7135929
doi: 10.1093/genetics/iyad073
pmc: PMC10213499
pii:
doi:
Substances chimiques
Retroelements
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIA NIH HHS
ID : R01 AG053269
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007491
Pays : United States
Organisme : NIA NIH HHS
ID : T32 AG023475
Pays : United States
Organisme : NIH HHS
ID : S10 OD023591
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA013330
Pays : United States
Informations de copyright
© The Author(s) 2023. Published by Oxford University Press on behalf of The Genetics Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
Déclaration de conflit d'intérêts
Conflicts of interest J.V. is a co-founder of Singulomics Inc., and MutaGentech Inc. The other authors declare no conflict of interest.
Références
Genes Dev. 2016 Apr 1;30(7):840-55
pubmed: 27036967
Annu Rev Cell Dev Biol. 2018 Oct 6;34:265-288
pubmed: 30044650
Aging Cell. 2016 Jun;15(3):542-52
pubmed: 27072046
Ann N Y Acad Sci. 1994 Jun 30;717:189-97
pubmed: 7518199
Nucleic Acids Res. 2021 Jan 8;49(D1):D605-D612
pubmed: 33237311
Annu Rev Physiol. 2013;75:645-68
pubmed: 23398157
Am J Hum Biol. 2006 May-Jun;18(3):422-5
pubmed: 16634019
Bioinformatics. 2009 Jul 15;25(14):1754-60
pubmed: 19451168
Cell Rep. 2018 Jun 19;23(12):3537-3550.e6
pubmed: 29924997
Nucleic Acids Res. 2022 Oct 14;50(18):10680-10694
pubmed: 36169232
Nucleic Acids Res. 2014 Feb;42(4):2512-24
pubmed: 24288375
Nucleic Acids Res. 2017 Jan 4;45(D1):D672-D678
pubmed: 27924039
Aging Cell. 2013 Apr;12(2):247-56
pubmed: 23360310
Mob DNA. 2015 Jun 02;6:11
pubmed: 26045719
Proc Natl Acad Sci U S A. 2016 Oct 4;113(40):11277-11282
pubmed: 27621458
J Immunol. 2011 Jan 15;186(2):649-56
pubmed: 21209287
Proc Natl Acad Sci U S A. 2014 Jul 22;111(29):E2967-76
pubmed: 25002478
Nucleic Acids Res. 2012 Mar;40(5):2032-40
pubmed: 22086961
Nucleic Acids Res. 2022 Jul 5;50(W1):W216-W221
pubmed: 35325185
Proc Natl Acad Sci U S A. 2013 May 28;110(22):9013-8
pubmed: 23667151
Cell. 2013 Jun 6;153(6):1194-217
pubmed: 23746838
Genome Biol. 2020 Sep 28;21(1):255
pubmed: 32988383
Nat Rev Genet. 2011 Aug 18;12(9):615-27
pubmed: 21850042
Nat Neurosci. 2013 May;16(5):529-31
pubmed: 23563579
Nucleic Acids Res. 2002 Jan 1;30(1):207-10
pubmed: 11752295
Mob DNA. 2016 May 06;7:9
pubmed: 27158268
Nat Protoc. 2009;4(1):44-57
pubmed: 19131956
Bioinformatics. 2015 May 15;31(10):1674-6
pubmed: 25609793
PLoS Genet. 2016 Sep 13;12(9):e1006281
pubmed: 27622269
EMBO J. 1985 Jan;4(1):155-61
pubmed: 2410252
Science. 2007 Jun 15;316(5831):1586-91
pubmed: 17569856
Int J Dev Biol. 2020;64(1-2-3):167-173
pubmed: 32659005
Proc Natl Acad Sci U S A. 2020 Sep 15;117(37):22890-22899
pubmed: 32843348
World J Biol Chem. 2010 May 26;1(5):151-9
pubmed: 21541000
J Immunol. 2014 Apr 15;192(8):3455-62
pubmed: 24706930
BMC Bioinformatics. 2006 Nov 30;7:520
pubmed: 17137497
Adv Ther. 2018 Jan;35(1):31-42
pubmed: 29209994
Science. 2015 Aug 28;349(6251):927-9
pubmed: 26229113
Nat Biotechnol. 2019 Aug;37(8):907-915
pubmed: 31375807
Methods Mol Biol. 2021;2282:1-15
pubmed: 33928566
Infect Immun. 2019 Aug 21;87(9):
pubmed: 31182620
Nucleic Acids Res. 2005 Apr 07;33(6):2052-9
pubmed: 15817569
Nucleic Acids Res. 2021 Jan 8;49(D1):D908-D915
pubmed: 33104800
PLoS Biol. 2019 May 16;17(5):e3000278
pubmed: 31095565
Nature. 2016 Oct 13;538(7624):257-259
pubmed: 27706136
PLoS One. 2009 Aug 31;4(8):e6838
pubmed: 19718442
BMC Bioinformatics. 2011 Aug 31;12:357
pubmed: 21880147
Nature. 2019 Feb;566(7742):73-78
pubmed: 30728521
Genetics. 2018 Mar;208(3):853-874
pubmed: 29487145
G3 (Bethesda). 2015 May 20;5(7):1493-502
pubmed: 25999583
Genome Biol. 2002;3(12):RESEARCH0085
pubmed: 12537574
Science. 2014 Dec 5;346(6214):1187-8
pubmed: 25477445
Genetics. 2022 Apr 4;220(4):
pubmed: 35266522
J Genet. 2014 Aug;93(2):379-88
pubmed: 25189233
Nat Methods. 2016 Oct;13(10):852-4
pubmed: 27595403
Comp Biochem Physiol A Mol Integr Physiol. 2017 Apr;206:17-23
pubmed: 28087331
Bioinformatics. 2015 Jul 15;31(14):2382-3
pubmed: 25765347
Science. 2008 May 23;320(5879):1077-81
pubmed: 18403677
Genetics. 2018 Oct;210(2):357-396
pubmed: 30287514
J Exp Biol. 2000 Sep;203(Pt 18):2713-22
pubmed: 10952872
Cell Rep. 2015 Apr 21;11(3):366-75
pubmed: 25865890
Cell. 2021 Oct 28;184(22):5506-5526
pubmed: 34715021
Genetica. 1994;93(1-3):79-90
pubmed: 7813919
Nat Commun. 2019 Sep 6;10(1):4022
pubmed: 31492840
Exp Gerontol. 2019 Nov;127:110733
pubmed: 31518666
EMBO J. 2004 Feb 25;23(4):772-9
pubmed: 14765112
Dis Model Mech. 2016 Jun 1;9(6):697-705
pubmed: 27101844
Nature. 2008 Jun 5;453(7196):798-802
pubmed: 18463631
Elife. 2020 Feb 13;9:
pubmed: 32053108
Genetics. 2015 Nov;201(3):843-52
pubmed: 26320097
Nature. 2001 Feb 15;409(6822):860-921
pubmed: 11237011
Development. 2019 Dec 20;146(24):
pubmed: 31862793
Aging (Albany NY). 2018 Apr 19;10(4):622-631
pubmed: 29677000
Cell Metab. 2019 Apr 2;29(4):871-885.e5
pubmed: 30853213
Nat Methods. 2017 Oct;14(10):959-962
pubmed: 28846090
Nat Methods. 2017 May;14(5):491-493
pubmed: 28319112
Bioinformatics. 2009 Aug 15;25(16):2078-9
pubmed: 19505943
Mob Genet Elements. 2017 Apr 19;7(3):1-18
pubmed: 28580197
Cell Rep. 2014 Jun 12;7(5):1481-1494
pubmed: 24882005
EMBO J. 2021 May 3;40(9):e106388
pubmed: 33634906
Genetica. 1992;86(1-3):1-11
pubmed: 1334902
Bioinformatics. 2010 Mar 15;26(6):841-2
pubmed: 20110278
Nature. 2021 Aug;596(7870):43-53
pubmed: 34349292
Proc Natl Acad Sci U S A. 2005 Feb 22;102(8):3105-10
pubmed: 15708981
PLoS Genet. 2010 May 13;6(5):e1000950
pubmed: 20485564
Genome Res. 2016 Jun;26(6):745-55
pubmed: 27197217
PLoS Genet. 2022 Mar 3;18(3):e1010024
pubmed: 35239675
Elife. 2022 Aug 18;11:
pubmed: 35980024
Aging (Albany NY). 2020 Nov 24;12(24):24604-24622
pubmed: 33232282