Transposable elements and their role in aging

Yushkova, Elena; Moskalev, Alexey

doi:10.1016/j.arr.2023.101881

Cited by 11 publications

(5 citation statements)

References 241 publications

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“…ORF1p is expressed at steady-state throughout the brain, but whether there is a dynamic regulation of this expression is not known. Aging has unequivocally been linked to LINE-1 regulation 15,39 both as a trigger and as a consequence of LINE-1 activation but whether this is true for the brain has not been thoroughly investigated using ORF1p as a read-out. We therefore addressed the question whether advanced age (16-month-old mice) was paralleled by a dynamic regulation of ORF1p expression in the brain compared to young, three-month old mice.…”

Section: Resultsmentioning

confidence: 99%

Steady-state neuron-predominant LINE-1 encoded ORF1p protein and LINE-1 RNA increase with aging in the mouse and human brain

Bonnifet,

Sinnassamy,

Massiani-Beaudoin

et al. 2023

Preprint

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Recent studies have established a reciprocal causal link between aging and the activation of transposable elements, characterized in particular by a de-repression of LINE-1 retrotransposons. These LINE-1 elements represent 21% of the human genome, but only a minority of these sequences retain the coding potential essential for their mobility. LINE-1 encoded proteins can induce cell toxicity implicated in aging and neurodegenerative diseases. However, our knowledge of the expression and localization of LINE-1-encoded proteins in the central nervous system is limited. Using a novel approach combining atlas-based brain mapping with deep-learning algorithms on large-scale pyramidal brain images, we unveil a heterogeneous, neuron-predominant and widespread ORF1p expression throughout the murine brain at steady-state. In aged mice, ORF1p expression increases significantly which is corroborated in human post-mortem dopaminergic neurons by an increase in young LINE-1 elements including those with open reading frames. Mass spectrometry analysis of endogenous mouse ORF1p revealed novel, neuron-specific protein interactors. These findings contribute to a comprehensive description of the dynamics of LINE-1 and ORF1p expression in the brain at steady-state and in aging and provide insights on ORF1p protein interactions in the brain.

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Section: Resultsmentioning

confidence: 99%

Steady-state neuron-predominant LINE-1 encoded ORF1p protein and LINE-1 RNA increase with aging in the mouse and human brain

Bonnifet,

Sinnassamy,

Massiani-Beaudoin

et al. 2023

Preprint

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“…gambiae exposure to ivermectin. This variation in the TE expression in the face of aging stress appears to be universal, occurring in other dipterans such as D. melanogaster to nematodes and rodents (137). Even though aging stress causes similar impacts on such distinct groups of organisms, this does not extend to other types of stress—an elevated level of the same salinity stress, here, produces totally different expression patterns in An.…”

Section: Discussionmentioning

confidence: 99%

Limited stress and tissue-specific transcriptional and translational activity of transposable elements in mosquitoes

Melo,

Wallau

2024

Preprint

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The mobilization of transposable elements (TEs) can either negatively affect the host’s fitness or contribute to the species evolution. TE protein expression is the first stage for transposition, but organisms developed defenses to control it. The intensity of regulatory mechanisms can vary among tissues, and in response to stress, it may facilitate TE activation across different species. Using hundreds of RNA-Seq and mass spectrometry experiments we calculated TE expression on twelve mosquito species. Most mosquito TE families exhibit constitutive RNA expression with abundant lncRNA production, yet only a limited number of proteins are effectively produced, in a tissue-specific manner. Under natural conditions, TEs exhibit distinct expression in somatic and germinal tissues, notably with pronounced repression in ovaries, associated with increased PIWI and AGO3 expression. Following exposure to abiotic stress and viral infection, certain TE families undergo altered expression. However, some stressors have no effects on TEs, or cause opposite effects in distinct species. Furthermore, repression predominates over induction in most cases. These data suggest that while some proteins are synthesized, the majority of TE transcripts function in a regulatory capacity. We also propose that the conventional notion of TEs being more expressed under stress conditions may not be universally valid.GRAPHICAL ABSTRACT

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“…Yet, assuming that these transcripts are indeed transposon-encoded, their upregulation in the old Daphnia is interesting. There has been recently an explosion of studies demonstrating that reactivation of transposons, retrotransposons in particular, as a consequence of erosion of epigenetic regulation that occurs with age, significantly contributes to downstream damage (Cardelli 2018; Gorbunova et al 2021; Yushkova & Moskalev 2023; Liu et al 2023). If confirmed, the increased transposon activity in aging Daphnia may make this organism an attractive model for the research of transposon’s role in aging.…”

Section: Discussionmentioning

confidence: 99%

Post-senescence reproductive rebound inDaphniaassociated with reversal of age-related transcriptional changes

Dua,

Pearson,

Lowman

et al. 2024

Preprint

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A long-lived species of zooplankton microcrustaceans,Daphnia magna,sometimes exhibits late-life rebound of reproduction, briefly reversing reproductive senescence. Such events are often interpreted as terminal investment in anticipation of imminent mortality. We demonstrate that such post-senescence reproductive events (PSREs) neither cause not anticipate increased mortality. We analyze an RNAseq experiment comparing young, old reproductively senescent, and old PSREDaphniafemales. We first show that overall age-related transcriptional changes are dominated by the increase transcription of guanidine monophosphate synthases and guanylate cyclases, as well as two groups of presumed transposon-encoded proteins and by a drop in transcription of protein synthesis-related genes. We then focus on gene families and functional groups in which full or partial reversal of age-related transcriptional changes occur. This analysis reveals reversal, in the PSRE individuals, of age-related up-regulation of apolipoproteins D, lysosomal lipases, and peptidases and of age-related down-regulation of E3 ubiquitin kinases, V-type proton ATPases, and numerous proteins related to mitochondrial and muscle functions. While it is certain which of these changes enable reproductive rejuvenation, and which are by-products of processes that lead to it, we present some evidence that post-senescence reproductive events are associated with the reversal of age-related protein and lipid aggregates removal, apoptosis, and with restoration of mitochondrial integrity.

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Transposable elements and their role in aging

Cited by 11 publications

References 241 publications

Steady-state neuron-predominant LINE-1 encoded ORF1p protein and LINE-1 RNA increase with aging in the mouse and human brain

Steady-state neuron-predominant LINE-1 encoded ORF1p protein and LINE-1 RNA increase with aging in the mouse and human brain

Limited stress and tissue-specific transcriptional and translational activity of transposable elements in mosquitoes

Post-senescence reproductive rebound inDaphniaassociated with reversal of age-related transcriptional changes

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