biostudies-literatureUnknownMrabti CIntramural NIH HHSAging is the major risk factor for most human diseases and represents a major socio-economical challenge for modern societies. Despite its importance, the process of aging remains poorly understood. Epigenetic dysregulation has been proposed as a key driver of the aging process. Modifications in transcriptional networks and chromatin structure might be central to age-related functional decline. A prevalent feature described during aging is the overall reduction in heterochromatin, specifically marked by the loss of repressive histone modification, Histone 3 lysine 9 trimethylation (H3K9me3). However, the role of H3K9me3 in aging, especially in mammals, remains unclear. Here we show using a novel mouse strain, (TKOc), carrying a triple knockout of three methyltransferases responsible for H3bioRxiv : the preprint server for biology2024.07.24.604929https://www.ebi.ac.uk/biostudies/studies/S-EPMC11291141biostudies-literatureLoss of H3K9 trimethylation leads to premature aging.PMC11291141ZIA AG000679von Meyenn FOcampo AAlonso-Calleja APico SNaveiras OYang NBranchina CSchoenfeldt LHorvath SSen PBrooke RDesdin-Mico GParras AHaghani AMaroun CYPiao YDel Carmen Maza MMrabti CVilchez-Acosta ALuo SfalseLoss of H3K9 trimethylation leads to premature aging.Aging is the major risk factor for most human diseases and represents a major socio-economical challenge for modern societies. Despite its importance, the process of aging remains poorly understood. Epigenetic dysregulation has been proposed as a key driver of the aging process. Modifications in transcriptional networks and chromatin structure might be central to age-related functional decline. A prevalent feature described during aging is the overall reduction in heterochromatin, specifically marked by the loss of repressive histone modification, Histone 3 lysine 9 trimethylation (H3K9me3). However, the role of H3K9me3 in aging, especially in mammals, remains unclear. Here we show using a novel mouse strain, (TKOc), carrying a triple knockout of three methyltransferases responsible for H32024-01-01T00:00:00Z2024 Jul2025-04-06T19:28:59.4Z2025-04-06T19:28:59.4ZS-EPMC112911413909181110.1101/2024.07.24.604929