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Loss of histones in the aging genome can drastically impact the epigenetic landscape of the cell leading to altered chromatin structure and changes in gene expression profiles. In this study, we investigated the impact of age\u2010related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. We observed a global reduction of histones H1, H2A, H2B, H3, and H4 in aged RPE\/choroid but not in the neural retina. Transcriptomic analyses revealed significant downregulation of histones in aged RPE\/choroid including crucial elements of the histone locus body (HLB) complex involved in histone pre\u2010mRNA processing. Knockdown of <jats:italic>HINFP<\/jats:italic>, a key HLB component, in human RPE cells induced histone loss, senescence, and the upregulation of senescence\u2010associated secretory phenotype (SASP) markers. Replicative senescence and chronological aging in human RPE cells similarly resulted in progressive histone loss and acquisition of the SASP. Immunostaining of human retina sections revealed histone loss in RPE with age. Acetyl\u2010histone profiling in aged mouse RPE\/choroid revealed a specific molecular signature with loss of global acetyl\u2010histone levels, including H3K14ac, H3K56ac, and H4K16ac marks. These findings strongly demonstrate histone loss as a unique feature of RPE aging and provide critical insights into the potential mechanisms linking histone dynamics, cellular senescence, and aging.<\/jats:p>","DOI":"10.1111\/acel.14108","type":"journal-article","created":{"date-parts":[[2024,2,26]],"date-time":"2024-02-26T19:10:55Z","timestamp":1708974655000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Histone deficiency and hypoacetylation in the aging retinal pigment epithelium"],"prefix":"10.1111","volume":"23","author":[{"given":"Sushil K.","family":"Dubey","sequence":"first","affiliation":[{"name":"Department of Surgery East Tennessee State University  Johnson City Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rashmi","family":"Dubey","sequence":"additional","affiliation":[{"name":"Department of Surgery East Tennessee State University  Johnson City Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subhash C.","family":"Prajapati","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics University of Virginia  Charlottesville Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyungsik","family":"Jung","sequence":"additional","affiliation":[{"name":"Department of Surgery East Tennessee State University  Johnson City Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kabhilan","family":"Mohan","sequence":"additional","affiliation":[{"name":"Department of Surgery East Tennessee State University  Johnson City Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinan","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Computer Science University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Roney","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenjian","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Surgery East Tennessee State University  Johnson City Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Abney","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology and Visual Sciences University of Kentucky  Lexington Kentucky USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michelle M.","family":"Giarmarco","sequence":"additional","affiliation":[{"name":"Department of Ophthalmology University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro G.","family":"Hernandez","sequence":"additional","affiliation":[{"name":"Roy J. 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