期刊
BRIEFINGS IN FUNCTIONAL GENOMICS
卷 21, 期 1, 页码 24-34出版社
OXFORD UNIV PRESS
DOI: 10.1093/bfgp/elab012
关键词
cellular senescence; nuclear organization; chromatin; epigenome; aging
资金
- National Institutes of Health [T32AG041688, T32GM128596, R01AG050582]
The article provides an overview of the nuclear changes that occur in different forms of senescence, including changes in chromatin state and composition, three-dimensional organization of the genome, nuclear envelope, and accessibility of repetitive genomic regions. These changes are shared across all forms of senescence, indicating that nuclear organization plays a fundamental role in the senescent state and interaction of senescent cells with the surrounding tissue.
Cellular senescence is the irreversible cell cycle arrest in response to DNA damage. Because senescent cells accumulate with age and contribute to chronic inflammation, they are promising therapeutic targets for healthspan extension. The senescent phenotype can vary depending on cell type and on the specific insults that induce senescence. This variability is also reflected in the extensive remodeling of the genome organization within the nucleus of senescent cells. Here, we give an overview of the nuclear changes that occur in different forms of senescence, including changes to chromatin state and composition and to the three-dimensional organization of the genome, as well as alterations to the nuclear envelope and to the accessibility of repetitive genomic regions. Many of these changes are shared across all forms of senescence, implicating nuclear organization as a fundamental driver of the senescent state and of how senescent cells interact with the surrounding tissue.
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