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Epigenetic Changes During Cellular Senescence

Cellular senescence refers to the permanent growth arrest of cells, characterized by a loss of replicative capacity and altered cellular function. This process plays a crucial role in aging and age-related diseases. Epigenetic changes, which involve modifications to the structure and function of DNA without altering the underlying genetic code, have been found to be closely associated with cellular senescence.

1. DNA Methylation

One of the key epigenetic changes observed during cellular senescence is alterations in DNA methylation patterns. DNA methylation involves the addition of a methyl group to the DNA molecule, typically occurring at cytosine residues within CpG dinucleotides. During cellular senescence, there is a global hypomethylation of DNA, leading to genomic instability and activation of transposable elements. Additionally, specific regions of the genome, such as tumor suppressor genes, can undergo hypermethylation, resulting in their silencing and loss of function.

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2. Histone Modifications

Histones are proteins that help package DNA into a compact structure called chromatin. Various modifications, such as acetylation, methylation, phosphorylation, and ubiquitination, can occur on histone proteins, influencing gene expression. In cellular senescence, there is a shift towards a repressive chromatin state, characterized by increased levels of repressive histone marks, such as H3K9me3 and H3K27me3. This leads to the silencing of genes involved in cell cycle regulation and DNA repair, contributing to the senescent phenotype.

3. Non-Coding RNAs

Non-coding RNAs (ncRNAs) are RNA molecules that do not code for proteins but play important regulatory roles in gene expression. During cellular senescence, there is dysregulation of various ncRNAs, including long non-coding RNAs (lncRNAs) and microRNAs (miRNAs). These ncRNAs can interact with DNA, RNA, and proteins to modulate gene expression networks involved in senescence-associated processes, such as cell cycle arrest, inflammation, and senescence-associated secretory phenotype (SASP) activation.

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4. Chromatin Remodeling

Chromatin remodeling refers to the dynamic changes in chromatin structure that allow or restrict access to DNA, thereby influencing gene expression. During cellular senescence, there is a remodeling of chromatin architecture, leading to the formation of senescence-associated heterochromatin foci (SAHF). These SAHFs are highly condensed chromatin domains enriched with repressive histone marks and DNA-binding proteins, contributing to the stable silencing of genes involved in cell proliferation and senescence escape.

In conclusion, cellular senescence is accompanied by significant epigenetic changes, including alterations in DNA methylation, histone modifications, dysregulation of non-coding RNAs, and chromatin remodeling. These epigenetic modifications contribute to the establishment and maintenance of the senescent phenotype, impacting various cellular processes and ultimately influencing longevity and age-related diseases.

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Keywords: senescence, cellular, chromatin, epigenetic, changes, during, modifications, methylation, histone