Repetitive Elements as a Transcriptomic Biomarker of Aging

Retrotransposons are receiving more attention in the context of aging these days. They are the remnants of ancient viruses, capable of copying themselves around the genome. The mechanisms repressing this copying tend to fail with age, and retrotransposons become a potential source of DNA damage and metabolic disarray. They are not the only class of repetitive elements in the genome, however. Here, researchers discuss the broader category of repetitive elements and their increasing presence with advancing age. Assessing repetitive element activity, such as by looking for them in the transcriptome, may be a potential biomarker of biological age.

One particularly large and often-ignored fraction of the human genome (more than 60%) is composed of repetitive elements (RE). These include: types 1 and 2 transposons (retrotransposons and DNA transposons, respectively), some of which can self-copy and reinsert into new locations; terminal repeats at the ends of retrotransposons; and tandem repeats, including sequences common to centromeres, chromatin, and other structured genome regions. Most RE are chromatinized and suppressed, but certain retrotransposons remain active in humans and may be involved in aging. Indeed, studies in mice and other model organisms have shown that active/transposable RE, in particular, contribute to the aging process, although most evidence points to RE activation later in life (e.g., in senescence).

The potential for RE in general to serve as a transcriptomic marker of aging has not been investigated, especially in humans, but we and others have reported a generic accumulation of RE transcripts (i.e., not only active RE) in age-related neurodegenerative processes and diseases. Evidence also indicates that chromatin maintenance declines with aging, which could increase general transcriptional accessibility of RE. As such, age-related changes in global RE transcript levels could be a good transcriptomic/mechanistic marker of aging.

Here, we used multiple RNA-seq datasets generated from human samples and Caenorhabditis elegans and found that most RE transcripts (a) accumulate progressively with aging; (b) can be used to accurately predict age; and (c) may be a good marker of biological age. The strong RE/aging correlations we observed are consistent with growing evidence that RE transcripts contribute directly to aging and disease.

Link: https://doi.org/10.1111/acel.13167

Comments

I'm not an expert on any of this, but this wouldn't be very helpful for testing anti-aging therapeutics, right? Once the genes are copied around, I don't think any of the proposed anti-aging modalities would "clean them up" - so what's exactly the point here?

I suppose you could do it periodically to see if the rate of change has gone down, but this sounds like irreversible loss of information.

I want to make it clear that I am asking the question not because I'm trying to imply that it's useless, but I'm curious to know how it fits in!

Posted by: Arshan at June 18th, 2020 9:54 PM

The point to me is that these endogenous retroviruses may be a root cause of aging. The abstract says, "The strong RE/aging correlations we observed are consistent with growing evidence that RE transcripts contribute directly to aging and disease."

Posted by: NY2LA at June 19th, 2020 3:42 AM

@NY2LA

Endogenous viruses being one of the root causes of adding wild be too simple and easy. We have an evolutionary by burden of being descendents of small rodent-like creatures which survived the meteorite that kills the dinosaurs. That creature read probably short lived with sorry generations . Such a creature doesn't need adaptations for long live, nor advanced regenerative capabilities .

In fact we have evolved those adaptations back like tricrhomate vision.

Posted by: Cuberat at June 26th, 2020 1:17 PM

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