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Abstract
36 tissue-specific epigenetic clocks were developed based on histone modifications, demonstrating strong resilience to technical and biological noise.
- Histone modifications may provide a more effective approach for predicting biological age compared to traditional DNA methylation-based methods.
- The clocks were validated using publicly available datasets across six tissue types and six histone marks, showing performance similar to established DNA methylation clocks.
- Biological age acceleration was detected in leukemia samples, and age reversal was observed following therapeutic interventions.
- Many aging-associated loci exhibited nonlinear changes, with peak modification levels occurring at midlife, indicating complex dynamics in epigenetic aging.
- Age-related fragmentation of super enhancer regions suggests increasing chromatin disorganization as organisms age.
- Histone-based clocks were also applicable in species lacking DNA methylation, indicating their evolutionary conservation as aging biomarkers.
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