Universal DNA methylation age across mammalian tissues

Abstract

Aging, often considered a result of random cellular damage, can be accurately estimated using DNA methylation profiles, the foundation of pan-tissue epigenetic clocks. Here, we demonstrate the development of universal pan-mammalian clocks, using 11,754 methylation arrays from our Mammalian Methylation Consortium, which encompass 59 tissue types across 185 mammalian species. These predictive models estimate mammalian tissue age with high accuracy (r > 0.96). Age deviations correlate with human mortality risk, mouse somatotropic axis mutations and caloric restriction. We identified specific cytosines with methylation levels that change with age across numerous species. These sites, highly enriched in polycomb repressive complex 2-binding locations, are near genes implicated in mammalian development, cancer, obesity and longevity. Our findings offer new evidence suggesting that aging is evolutionarily conserved and intertwined with developmental processes across all mammals.

Increased hippocampal epigenetic age in the Ts65Dn Mouse Model of Down Syndrome

“…Although larger samples are needed, our study supports the use of the Ts65Dn model to decipher the molecular mechanisms underlying the progeroid DS phenotype. Finally, our study supports the use of the DNAge® clock and, possibly, other recently developed mouse epigenetic clocks (Lu et al 2023; Zhou et al 2022), as biomarkers of biological age. Such tools might be exploited to monitor the impact of disease and disease-modifying interventions in DS.…”

“…Murine models are largely employed in the study of ageing and age-related disease (Palliyaguru et al 2021) and mouse epigenetic biomarkers of age have been developed (Coninx et al 2020; Lu et al 2023; Han et al 2018; Zhou et al 2022; Wang & Lemos 2019). So far, however, these epigenetic clocks have been applied to a limited extent and, to the best of our knowledge, no data are available for mouse models of DS.…”

Integrative analysis of the methylome and transcriptome of tomato fruit (Solanum lycopersicumL.) induced by postharvest handling

“…The fruit industry commonly uses color or other quality traits to define produce age. Instead, our data implied that methylome and transcriptome indicated age may be more accurate than cellular or chronological age 88 . These fruit genomic molecular fingerprints could potentially serve as quality biomarkers for differentiating fruit internal quality parameters from external appearance, therefore contributing to a reduction in postharvest waste in the future.…”

Aging Differentially Alters the Transcriptome and Landscape of Chromatin Accessibility in the Male and Female Mouse Hippocampus

“…Histone variants and histone post-translational modifications are associated with open or closed chromatin, and in general, CpG island methylation is correlated with decreased chromatin accessibility 113,114,173 . Changes in the expression of histone proteins, as well as altered histone modifications and DNA hypo- or hyper-methylation are widely documented to occur during aging; indeed, aging-related changes in DNA methylation serve as the basis of epigenetic clocks 124,125,174,175 . Therefore, loss of histone proteins, loss of repressive histone marks and changes in DNA methylation likely contribute to the aging-related opening in chromatin accessibility we detected in the male and female hippocampus.…”