Retro-age: A unique epigenetic biomarker of aging captured by DNA methylation states of retroelements.

TitleRetro-age: A unique epigenetic biomarker of aging captured by DNA methylation states of retroelements.
Publication TypeJournal Article
Year of Publication2024
AuthorsNdhlovu LC, Bendall ML, Dwaraka V, Pang APS, Dopkins N, Carreras N, Smith R, Nixon DF, Corley MJ
JournalAging Cell
Paginatione14288
Date Published2024 Aug 02
ISSN1474-9726
Abstract

Reactivation of retroelements in the human genome has been linked to aging. However, whether the epigenetic state of specific retroelements can predict chronological age remains unknown. We provide evidence that locus-specific retroelement DNA methylation can be used to create retroelement-based epigenetic clocks that accurately measure chronological age in the immune system, across human tissues, and pan-mammalian species. We also developed a highly accurate retroelement epigenetic clock compatible with EPICv.2.0 data that was constructed from CpGs that did not overlap with existing first- and second-generation epigenetic clocks, suggesting a unique signal for epigenetic clocks not previously captured. We found retroelement-based epigenetic clocks were reversed during transient epigenetic reprogramming, accelerated in people living with HIV-1, and responsive to antiretroviral therapy. Our findings highlight the utility of retroelement-based biomarkers of aging and support a renewed emphasis on the role of retroelements in geroscience.

DOI10.1111/acel.14288
Alternate JournalAging Cell
PubMed ID39092674
Grant ListR01AG082056 / NH / NIH HHS / United States
R01HL160392 / NH / NIH HHS / United States
R01MH134391 / NH / NIH HHS / United States
UM1AI164559 / NH / NIH HHS / United States