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Retroelement-Age Clocks: Epigenetic Age Captured by Human Endogenous Retrovirus and LINE-1 DNA methylation states

Ndhlovu, L.; Bendall, M.; Dwaraka, V. B.; Pang, A. P.; Dopkins, N.; Carreras, N.; Smith, R.; Nixon, D.; Corley, M. J.

2023-12-07 immunology
10.1101/2023.12.06.570422 bioRxiv
Show abstract

Human endogenous retroviruses (HERVs), the remnants of ancient viral infections embedded within the human genome, and long interspersed nuclear elements 1 (LINE-1), a class of autonomous retrotransposons, are silenced by host epigenetic mechanisms including DNA methylation. The resurrection of particular retroelements has been linked to biological aging. Whether the DNA methylation states of locus specific HERVs and LINEs can be used as a biomarker of chronological age in humans remains unclear. We show that highly predictive epigenetic clocks of chronological age can be constructed from retroelement DNA methylation states in the immune system, across human tissues, and pan-mammalian species. We found retroelement epigenetic clocks were reversed during transient epigenetic reprogramming, accelerated in people living with HIV-1, responsive to antiretroviral therapy, and accurate in estimating long-term culture ages of human brain organoids. Our findings support the hypothesis of epigenetic dysregulation of retroelements as a potential contributor to the biological hallmarks of aging.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.