Age‐associated de‐repression of retrotransposons in the
            <i>Drosophila</i>
            fat body, its potential cause and consequence

Chen, Haiyang; Zheng, Xiaobin; Xiao, Danqing; Zheng, Yixian

doi:10.1111/acel.12465

Cited by 70 publications

(89 citation statements)

References 45 publications

(59 reference statements)

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“…Similarly, we also observe an increase in somatic TE transposition with age in the fat body. DNA double-strand breaks increase with age in the fat body (16), and we show this DNA damage also accumulates at a younger age in Dicer-2 mutant flies with high levels of TEs. The age-related increase in TE transcript levels as well as TE mobilization were suppressed by DR.…”

Section: Discussionmentioning

confidence: 53%

“…Increased DNA damage has been observed in aging fat body nuclei, as assayed by γH2Av immunostaining (16). Our finding of a repression of TE expression with increased Dicer-2 expression led us to investigate whether genomic integrity was similarly compromised in animals with disrupted RNAi/heterochromatin pathways and increased TE activity.…”

Section: Age-related Increases In Te Expression Are Attenuated By Genmentioning

confidence: 92%

“…The Drosophila genome is rich in retroviral-like long terminal repeat (LTR) and long interspersed nuclear elements (LINEs) (30), and activation of both LINEs and LTRs has been observed in the fly nervous system and fat body during aging (15,16). Because heterochromatin integrity declines with age in multiple model systems (1), we hypothesized that a loss of heterochromatin in regions highly enriched with TEs would show a correlated increase in TE expression with age.…”

Section: Expression Of Genes Located Within Heterochromatin Increasesmentioning

confidence: 99%

“…Overexpressing TE RNAs is sufficient to cause cytotoxicity, and inhibiting expression of these TEs causes reversal of both senescence and cytotoxic phenotypes (10,11). TE activation has been observed with age in mice (8,12), as well as C. elegans (13), yeast (14), Drosophila (15,16), and senescent human tissue culture cells (7).…”

mentioning

confidence: 99%

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Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

Wood

Jones

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

149

179

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Transposable elements (TEs) are mobile genetic elements, highly enriched in heterochromatin, that constitute a large percentage of the DNA content of eukaryotic genomes. Aging in Drosophila melanogaster is characterized by loss of repressive heterochromatin structure and loss of silencing of reporter genes in constitutive heterochromatin regions. Using next-generation sequencing, we found that transcripts of many genes native to heterochromatic regions and TEs increased with age in fly heads and fat bodies. A dietary restriction regimen, known to extend life span, repressed the age-related increased expression of genes located in heterochromatin, as well as TEs. We also observed a corresponding age-associated increase in TE transposition in fly fat body cells that was delayed by dietary restriction. Furthermore, we found that manipulating genes known to affect heterochromatin structure, including overexpression of Sir2, Su(var)3-9, and Dicer-2, as well as decreased expression of Adar, mitigated age-related increases in expression of TEs. Increasing expression of either Su(var)3-9 or Dicer-2 also led to an increase in life span. Mutation of Dicer-2 led to an increase in DNA double-strand breaks. Treatment with the reverse transcriptase inhibitor 3TC resulted in decreased TE transposition as well as increased life span in TE-sensitized Dicer-2 mutants. Together, these data support the retrotransposon theory of aging, which hypothesizes that epigenetically silenced TEs become deleteriously activated as cellular defense and surveillance mechanisms break down with age. Furthermore, interventions that maintain repressive heterochromatin and preserve TE silencing may prove key to preventing damage caused by TE activation and extending healthy life span.aging | heterochromatin | transposable elements | dietary restriction | silencing

show abstract

Section: Discussionmentioning

confidence: 53%

Section: Age-related Increases In Te Expression Are Attenuated By Genmentioning

confidence: 92%

Section: Expression Of Genes Located Within Heterochromatin Increasesmentioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

Wood

Jones

Jiang

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

149

179

View full text Add to dashboard Buy / Rent full text

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“…TE reactivation and transposition has been shown to correlate with chromosomal rearrangements, double-strand DNA breaks and apoptosis78. Phosphorylation of the histone variant H2A.v (γ-H2A.v) during DNA repair serves as a reliable marker of double-strand DNA breaks and has been shown to correlate with increased TE activity in the fat body928. Using immunofluorescent microscopy, we observed an increase in the intensity of γ-H2A.v staining in piwi mutants relative to controls (Fig.…”

Section: Resultsmentioning

confidence: 99%

A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan

et al. 2016

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In gonadal tissues, the Piwi-interacting (piRNA) pathway preserves genomic integrity by employing 23–29 nucleotide (nt) small RNAs complexed with argonaute proteins to suppress parasitic mobile sequences of DNA called transposable elements (TEs). Although recent evidence suggests that the piRNA pathway may be present in select somatic cells outside the gonads, the role of a non-gonadal somatic piRNA pathway is not well characterized. Here we report a functional somatic piRNA pathway in the adult Drosophila fat body including the presence of the piRNA effector protein Piwi and canonical 23–29 nt long TE-mapping piRNAs. The piwi mutants exhibit depletion of fat body piRNAs, increased TE mobilization, increased levels of DNA damage and reduced lipid stores. These mutants are starvation sensitive, immunologically compromised and short-lived, all phenotypes associated with compromised fat body function. These findings demonstrate the presence of a functional non-gonadal somatic piRNA pathway in the adult fat body that affects normal metabolism and overall organismal health.

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Age‐associated de‐repression of retrotransposons in the Drosophila fat body, its potential cause and consequence

Cited by 70 publications

References 45 publications

Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

Chromatin-modifying genetic interventions suppress age-associated transposable element activation and extend life span in Drosophila

A somatic piRNA pathway in the Drosophila fat body ensures metabolic homeostasis and normal lifespan

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