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Histone mark age of human tissues and cells

de Lima Camillo, L. P.; Asif, M. H.; Horvath, S.; Larschan, E.; Singh, R.

2023-08-23 systems biology
10.1101/2023.08.21.554165 bioRxiv
Show abstract

BackgroundAging involves intricate epigenetic changes, with histone modifications playing a pivotal role in dynamically regulating gene expression. Our research comprehensively analyzes seven key histone modifications across various tissues to understand their behavior during human aging and formulate age prediction models. ResultsThese histone-centric prediction models exhibit remarkable accuracy and resilience against experimental and artificial noise. They showcase comparable efficacy when compared with DNA methylation age predictors through simulation experiments. Intriguingly, our gene set enrichment analysis pinpoints vital developmental pathways crucial for age prediction. Unlike in DNA methylation age predictors, genes previously recognized in animal studies as integral to aging are amongst the most important features of our models. We also introduce a pan-histone-mark, pan-tissue age predictor that operates across multiple tissues and histone marks, reinforcing that age-related epigenetic markers are not restricted to particular histone modifications. ConclusionOur findings underscore the potential of histone marks in crafting robust age predictors and shed light on the intricate tapestry of epigenetic alterations in aging.

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