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Age-related histone loss and altered histone acetylation in mouse retinal pigment epithelium.

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Mus musculus

PROVIDER: GSE236221 | GEO | 2023/07/15

REPOSITORIES: GEO

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Project description:Histones are pivotal carriers of epigenetic information through post-translational modifications (PTMs), crucial for regulating gene expression, proper cellular function and maintaining cell identity. Perturbations in histone levels within the aging genome can profoundly impact chromatin structure and gene expression profiles. In this study, we examined the effects of age-related changes on histone levels and histone acetylation in the retinal pigment epithelium (RPE) and retina of mice. Our findings revealed a global reduction in histones H1, H2A, H2B, H3, and H4 within the aged RPE/choroid, while the neural retina remained unaffected. Transcriptome analysis unveiled a significant downregulation of histone genes in the aged RPE/choroid, including key components of the histone locus body (HLB) complex involved in histone pre-mRNA processing. Knockdown of HINFP, a critical HLB component, in human RPE cells resulted in histone loss, induction of senescence, and upregulation of senescence-associated secretory phenotype (SASP) markers. Replicative aging of human RPE cells exhibited progressive histone loss and acquisition of the SASP phenotype. Immunostaining of human retina sections demonstrated a gradual decline in histones within the aging RPE. Additionally, aging in mice RPE/choroid led to diminished global histone acetylation levels, particularly H3K14ac, H3K56ac, and H4K16ac marks. These alterations in histone acetylation were metabolically driven and correlated with changes in acetyl-CoA abundance. Collectively, our findings highlight the characteristic loss of histones as a hallmark of aging in the RPE/choroid, shedding light on potential mechanisms linking histone dynamics, cellular senescence, and age-related functional changes in RPE cells.

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