Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues

Cecco, Marco De; Criscione, Steven W.; Peterson, Abigail L.; Neretti, Nicola; Sedivy, John M.; Kreiling, Jill A.

doi:10.18632/aging.100621

Cited by 252 publications

(259 citation statements)

References 65 publications

(88 reference statements)

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“…The biotype changes observed may reflect a burst of “transcriptional noise” in DGF allografts in response to IRI, as a direct result of changes in the methylation status of promoters and intragenic regions (Huh, Zeng, Park, & Yi, 2013). These observations are also consistent with the derepression of LINE elements in ageing cells (De Cecco et al, 2013). …”

Section: Discussionsupporting

confidence: 88%

A molecular signature for delayed graft function

et al. 2018

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Chronic kidney disease and associated comorbidities (diabetes, cardiovascular diseases) manifest with an accelerated ageing phenotype, leading ultimately to organ failure and renal replacement therapy. This process can be modulated by epigenetic and environmental factors which promote loss of physiological function and resilience to stress earlier, linking biological age with adverse outcomes post‐transplantation including delayed graft function (DGF). The molecular features underpinning this have yet to be fully elucidated. We have determined a molecular signature for loss of resilience and impaired physiological function, via a synchronous genome, transcriptome and proteome snapshot, using human renal allografts as a source of healthy tissue as an in vivo model of ageing in humans. This comprises 42 specific transcripts, related through IFNγ signalling, which in allografts displaying clinically impaired physiological function (DGF) exhibited a greater magnitude of change in transcriptional amplitude and elevated expression of noncoding RNAs and pseudogenes, consistent with increased allostatic load. This was accompanied by increased DNA methylation within the promoter and intragenic regions of the DGF panel in preperfusion allografts with immediate graft function. Pathway analysis indicated that an inability to sufficiently resolve inflammatory responses was enabled by decreased resilience to stress and resulted in impaired physiological function in biologically older allografts. Cross‐comparison with publically available data sets for renal pathologies identified significant transcriptional commonality for over 20 DGF transcripts. Our data are clinically relevant and important, as they provide a clear molecular signature for the burden of “wear and tear” within the kidney and thus age‐related physiological capability and resilience.

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Section: Discussionsupporting

confidence: 88%

A molecular signature for delayed graft function

et al. 2018

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“…In spite of the abundance and the putative role of transposable elements in shaping genome variation in bivalves (Zhang et al 2012), their response to environmental stressors remains poorly understood (Casacuberta and González 2013;Miousse et al 2015). The expression of retrotransposable elements usually increases with age; however, it could be reduced by caloric restriction (De Cecco et al 2013), and previous studies, though in marine mussels, showed that feeding rates are reduced with age (Bellas et al 2014). Moreover, it was documented that adult freshwater mussels have the ability to detect toxicants in the water and consequently close their valves to avoid exposure (Liu et al 2016).…”

Section: Effects Of Individual Factors On Gene Expression In Kidneymentioning

confidence: 99%

Transcriptomic responses of the endangered freshwater mussel Margaritifera margaritifera to trace metal contamination in the Dronne River, France

Bertucci

Pierron

Thébault

et al. 2017

Environ Sci Pollut Res

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The freshwater pearl mussel Margaritifera margaritifera is one of the most threatened freshwater bivalves worldwide. In this study, we aimed (i) to study the processes by which water quality might affect freshwater mussels in situ and (ii) to provide insights into the ecotoxicological significance of water pollution to natural populations in order to provide necessary information to enhance conservation strategies. M. margaritifera specimens were sampled in two close sites located upstream or downstream from an illegal dumping site. The renal transcriptome of these animals was assembled and gene transcription determined by RNA-seq. Correlations between transcription levels of each single transcript and the bioaccumulation of nine trace metals, age (estimated by sclerochronology), and condition index were determined in order to identify genes likely to respond to a specific factor. Amongst the studied metals, Cr, Zn, Cd, and Ni were the main factors correlated with transcription levels, with effects on translation, apoptosis, immune response, response to stimulus, and transport pathways.However, the main factor explaining changes in gene transcription appeared to be the age of individuals with a negative correlation with the transcription of retrotransposon-related genes. To investigate this effect further, mussels were classified into three age classes. In young, middle-aged and old animals, transcription levels were mainly explained by Cu, Zn and age, respectively. This suggests differences in the molecular responses of this species to metals during its lifetime that must be better assessed in future ecotoxicology studies.

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“…Small numbers of transposable element genes, mostly retroposons, and pseudo-genes were both up-and down-regulated during leaf senescence. This contrasts to animal cells, where a general increase in expression and mobility of transposable element genes has been observed in older somatic cells (De Cecco et al, 2013;Li et al, 2013a). A gene ontology (GO) analysis was performed on this list of SURGs and SDRGs, and enriched biological processes with false discovery rates below 1% are shown in Table I.…”

Section: Rna-seq Gene Expression Analysismentioning

confidence: 99%

A Genome-Wide Chronological Study of Gene Expression and Two Histone Modifications, H3K4me3 and H3K9ac, during Developmental Leaf Senescence

et al. 2015

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The genome-wide abundance of two histone modifications, H3K4me3 and H3K9ac (both associated with actively expressed genes), was monitored in Arabidopsis (Arabidopsis thaliana) leaves at different time points during developmental senescence along with expression in the form of RNA sequencing data. H3K9ac and H3K4me3 marks were highly convergent at all stages of leaf aging, but H3K4me3 marks covered nearly 2 times the gene area as H3K9ac marks. Genes with the greatest fold change in expression displayed the largest positively correlated percentage change in coverage for both marks. Most senescence up-regulated genes were premarked by H3K4me3 and H3K9ac but at levels below the whole-genome average, and for these genes, gene expression increased without a significant increase in either histone mark. However, for a subset of genes showing increased or decreased expression, the respective gain or loss of H3K4me3 marks was found to closely match the temporal changes in mRNA abundance; 22% of genes that increased expression during senescence showed accompanying changes in H3K4me3 modification, and they include numerous regulatory genes, which may act as primary response genes.

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Transposable elements become active and mobile in the genomes of aging mammalian somatic tissues

Cited by 252 publications

References 65 publications

A molecular signature for delayed graft function

A molecular signature for delayed graft function

Transcriptomic responses of the endangered freshwater mussel Margaritifera margaritifera to trace metal contamination in the Dronne River, France

A Genome-Wide Chronological Study of Gene Expression and Two Histone Modifications, H3K4me3 and H3K9ac, during Developmental Leaf Senescence

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