Thesis
Genomic landscape during cellular senescence
Master of Science (M.S.), Drexel University
Jun 2019
DOI:
https://doi.org/10.17918/fcrg-t642
Abstract
Cellular senescence is a cell fate defined by an irreversible cell-cycle arrest, which occurs in primary cells after a defined number of population doublings or in response to DNA damage, oxidative stress, oncogenic conversion, or metabolic imbalance. Accumulation of senescent cells is a universal hallmark of age-related pathologies suggesting these cells contribute to age-related susceptibility to disease. Previous work from our laboratory has shown that longevity-enhancing regimens including rapamycin treatment delays cellular senescence, extending the replicative lifespan of cells in vitro. Surprisingly, specific combinatorial treatments completely prevent senescence, allowing cells to proliferate at a very slow rate for over a year in culture. Previously performed transcriptome-wide analysis revealed that human cells treated with the combination regimen fail to produce a senescent profile notably at high population doublings. To gain insight into the effect of the combinatorial treatment and its role in the extension of cellular lifespan, it is important to uncover the genetic implications of this treatment and its impact on the process of chromatin structure establishment and maintenance. In a systematical approach using ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing), we have identified changes in the chromatin accessibility at senescence-associated genes following combinatorial treatment of human cardiac fibroblasts. The results demonstrate that pro-longevity treatments prevent chromatin remodeling required to establish the senescent state.
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Details
- Title
- Genomic landscape during cellular senescence
- Creators
- Manali Potnis - DU
- Contributors
- Christian Sell (Advisor) - Drexel University (1970-)
- Awarding Institution
- Drexel University
- Degree Awarded
- Master of Science (M.S.)
- Publisher
- Drexel University; Philadelphia, Pennsylvania
- Number of pages
- viii, 77 pages
- Resource Type
- Thesis
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; College of Medicine; Drexel University
- Other Identifier
- 10912; 991014632231004721