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Chromatin Structure in Senescent Cells

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Cellular Senescence and Tumor Suppression

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Abstract

The new millennium brought multiple discoveries of epigenetic events regulating the chromatin structure of normal and cancerous cells. Such renewed enthusiasm for chromatin studies was prompted by the development of new technologies and novel ideas that helped discover the “histone code.” It is now clear that posttranslational modifications of histone tails and insertion of histone variants regulate the structure of chromatin and, consequently, the fate of a cell during development, stem cell function, and cancer. Here, we review how the “emerging field of epigenetics in aging” has progressed, since it was found more than 30 years ago that old cells display decreased histone acetylation and increased reorganization of heterochromatin. We focus our discussion on structural changes of chromatin, the role of histone modifications and their modifiers, and highlight some paradigms and controversies regarding the opposite roles of class 1 and class 3 histone deacetylases in cellular senescence and tissue aging. We propose that an ever deregulated chromatin structure results in feed forward mechanisms of aberrant, tissue-specific gene expression and aging. Finally, we discuss how some drugs or hormones that target pathways regulated by histone modifiers can ameliorate some age-related dysfunctions.

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Acknowledgments

The Medrano laboratory is supported by National Institutes of Health grants (RO1 AG032135 and 2R01 CA84282) and a Senior Scholar Award from the Ellison Medical Foundation. HWR was supported by NIH training grant T32AG000183 We apologize for any omission but space limitations have prevented us to reference a large number of original papers and reviews.

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  1. Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza MS230, Houston, TX, 77030, USA

    Estela E. Medrano

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  1. Hunter W. Richards
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Correspondence to Estela E. Medrano .

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  1. Cancer Research UK, University of Glasgow, Switchback Road, Glasgow, G61 1BD, United Kingdom

    Peter D. Adams

  2. Dept. Molecular & Cell Biology &, Brown University, Ship Street 70, Providence, 02912, U.S.A.

    John M. Sedivy

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Richards, H.W., Medrano, E.E. (2010). Chromatin Structure in Senescent Cells. In: Adams, P., Sedivy, J. (eds) Cellular Senescence and Tumor Suppression. Springer, New York, NY. https://doi.org/10.1007/978-1-4419-1075-2_6

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