Histone modification clocks for robust cross-species biological age prediction and elucidating senescence regulation - PubMed
a day ago
- #aging
- #epigenetics
- #histone-modification
- Histone modifications offer a new method for biological age prediction, overcoming DNA methylation-based clock limitations.
- Developed 36 tissue-specific histone modification clocks using ChIP-seq data from six tissues and six histone marks.
- Clocks showed resilience to noise, comparable to DNA methylation clocks, and detected age acceleration in leukemia.
- Identified nonlinear aging trajectories with peak modification levels at midlife, revealing new epigenetic aging dynamics.
- Observed age-related fragmentation of super enhancer regions, indicating progressive chromatin disorganization.
- Validated a causal role of an H3K27ac peak near IGF2BP3 in cellular senescence via TRA2A expression regulation.
- Demonstrated histone-based clocks' applicability in Drosophila, highlighting evolutionary conservation and broader utility.
- Established histone modifications as robust, biologically meaningful aging biomarkers across species.