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.