Journal article
Metabolic Regulation of the Senescence Program
Innovation in aging, v 4(Suppl 1), pp 133-133
16 Dec 2020
Abstract
Cellular senescence is a cell fate defined by an irreversible cell-cycle arrest and a pro-inflammatory secretory profile. It is a consequence of a shift in metabolism and rearrangement of chromatin. Accumulation of senescent cells is a universal hallmark of age-related pathologies suggesting these cells contribute to age-related susceptibility to disease. Here, we examine the interplay between two metabolic inhibitors of senescence: Rapamycin treatment and Methionine restriction (metR). We report that a combination of methionine restriction and rapamycin induces a metabolic reprogramming that prevents activation of the senescence program in human fibroblasts. The treated cells continue to divide at a slow rate at a high passage and lack senescence-associated markers and inflammatory cytokines. Genome-wide chromatin accessibility analysis reflects chromatin remodeling with distinctly increased accessibility of heterochromatic regions in treated cells. Further, Transcriptome-wide analysis reveals increased expression of specific methyltransferases which alter the trimethylation of H3, one of the strongest hallmarks of open chromatin. This may represent a mechanistic link between a major hallmark of senescence and nuclear events required for senescence.
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Details
- Title
- Metabolic Regulation of the Senescence Program
- Creators
- Manali Potnis - Drexel UniversityTimothy Nacarelli - Drexel UniversityEishi Noguchi - Drexel UniversityAshley Azar - Drexel UniversityChristian Sell - Drexel University
- Publication Details
- Innovation in aging, v 4(Suppl 1), pp 133-133
- Publisher
- Oxford University Press
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; School of Biomedical Engineering, Science, and Health Systems
- Other Identifier
- 991020111270804721