Downregulation of transposable elements extends lifespan in Caenorhabditis elegans

被引:10
|
作者
Sturm, Adam [1 ,2 ]
Saskoi, Eva [1 ]
Hotzi, Bernadette [1 ]
Tarnoci, Anna [2 ]
Barna, Janos [2 ]
Bodnar, Ferenc [1 ]
Sharma, Himani [1 ]
Kovacs, Tibor [1 ]
Ari, Eszter [1 ,3 ,4 ]
Weinhardt, Nora [1 ]
Kerepesi, Csaba [5 ,6 ,7 ]
Perczel, Andras [8 ,9 ]
Ivics, Zoltan [10 ]
Vellai, Tibor [1 ,2 ,11 ]
机构
[1] Eotvos Lorand Univ, Dept Genet, H-1117 Budapest, Hungary
[2] Eotv Lorand Res Network ELKH ELTE Genet Res Grp, H-1117 Budapest, Hungary
[3] HCEMM BRC Metab Syst Biol Res Grp, H-6726 Szeged, Hungary
[4] Eotvos Lorand Res Network ELKH, Synthet & Syst Biol Unit, Biol Res Ctr, Inst Biochem, Temesvari Krt 62, H-6726 Szeged, Hungary
[5] Inst Comp Sci & Control SZTAK, Kende U 13-17, H-1111 Budapest, Hungary
[6] Brigham & Womens Hosp, Boston, MA 02115 USA
[7] Harvard Med Sch, Boston, MA 02115 USA
[8] Eotvos L Univ, Inst Chem, Lab Struct Chem & Biol, H-1117 Budapest, Hungary
[9] Eotvos Lorand Univ, Inst Chem, Hungarian Acad Sci MTA ELTE Prot Modelling Res Grp, H-1117 Budapest, Hungary
[10] Paul Ehrlich Inst, Div Med Biotechnol, D-63225 Langen, Germany
[11] Vellab Biotech Ltd, H-6722 Szeged, Hungary
基金
匈牙利科学研究基金会; 美国国家卫生研究院;
关键词
DNA METHYLATION; RETROTRANSPOSABLE ELEMENTS; HEAT-SHOCK; GENOME; PIWI; N-6-ADENINE; INSTABILITY; ACTIVATION; GENETICS; MUTATION;
D O I
10.1038/s41467-023-40957-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Mobility of transposable elements (TEs) frequently leads to insertional mutations in functional DNA regions. In the potentially immortal germline, TEs are effectively suppressed by the Piwi-piRNA pathway. However, in the genomes of ageing somatic cells lacking the effects of the pathway, TEs become increasingly mobile during the adult lifespan, and their activity is associated with genomic instability. Whether the progressively increasing mobilization of TEs is a cause or a consequence of ageing remains a fundamental problem in biology. Here we show that in the nematode Caenorhabditis elegans, the downregulation of active TE families extends lifespan. Ectopic activation of Piwi proteins in the soma also promotes longevity. Furthermore, DNA N6-adenine methylation at TE stretches gradually rises with age, and this epigenetic modification elevates their transcription as the animal ages. These results indicate that TEs represent a novel genetic determinant of ageing, and that N6-adenine methylation plays a pivotal role in ageing control.
引用
收藏
页数:18
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