Cellular Senescence Involves Gene Repression Through p53-p16/RB-E2F-DREAM Complex
06-13-2023“Our study enables us to envisage a global picture of genes and pathways dysregulated during senescence and provides novel evidence for involvement of p53/p16/RB-E2F-DREAM repressional targets in this complex cellular process.”
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BUFFALO, NY- June 13, 2023 – A new research paper was published in Aging (listed by MEDLINE/PubMed as "Aging (Albany NY)" and "Aging-US" by Web of Science) Volume 15, Issue 10, entitled, “Key elements of cellular senescence involve transcriptional repression of mitotic and DNA repair genes through the p53-p16/RB-E2F-DREAM complex.”
Cellular senescence is a dynamic stress response process that contributes to aging. From initiation to maintenance, senescent cells continuously undergo complex molecular changes and develop an altered transcriptome. Understanding how the molecular architecture of these cells evolve to sustain their non-proliferative state will open new therapeutic avenues to alleviate or delay the consequences of aging.
In this new study, seeking to understand these molecular changes, researchers Renuka Kandhaya-Pillai, Francesc Miro-Mur, Jaume Alijotas-Reig, Tamar Tchkonia, Simo Schwartz, James L. Kirkland, and Junko Oshima from the University of Washington, Vall d’Hebron Research Institute (VHIR), Vall d’Hebron Hospital, and the Mayo Clinic studied the transcriptomic profiles of endothelial replication-induced senescence and senescence induced by the inflammatory cytokine, TNF-α. The researchers previously reported gene expressional pattern, pathways, and the mechanisms associated with upregulated genes during TNF-α induced senescence.
“Here, we extend our work and find downregulated gene signatures of both replicative and TNF-α senescence were highly overlapped, involving the decreased expression of several genes associated with cell cycle regulation, DNA replication, recombination, repair, chromatin structure, cellular assembly, and organization.”
The team identified multiple targets of p53/p16-RB-E2F-DREAM that are essential for proliferation, mitotic progression, resolving DNA damage, maintaining chromatin integrity, and DNA synthesis that were repressed in senescent cells. They show that repression of multiple target genes in the p53/p16-RB-E2F-DREAM pathway collectively contributes to the stability of the senescent arrest. Their findings show that the regulatory connection between DREAM and cellular senescence may play a potential role in the aging process.
“This study suggests that the transcriptome signature of senescent cells goes beyond cell cycle arrest, with expression of multiple genes, from cell cycle to DNA repair to chromatin structure, being coordinately repressed to stably lock cells into this essentially non-proliferative state.”
Read the full study: DOI: https://doi.org/10.18632/aging.204743
Corresponding Author: Renuka Kandhaya-Pillai
Corresponding Email: renugene@uw.edu
Keywords: cellular senescence, cell cycle, DREAM complex, DNA repair
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About Aging-US:
Aging publishes research papers in all fields of aging research including but not limited, aging from yeast to mammals, cellular senescence, age-related diseases such as cancer and Alzheimer’s diseases and their prevention and treatment, anti-aging strategies and drug development and especially the role of signal transduction pathways such as mTOR in aging and potential approaches to modulate these signaling pathways to extend lifespan. The journal aims to promote treatment of age-related diseases by slowing down aging, validation of anti-aging drugs by treating age-related diseases, prevention of cancer by inhibiting aging. Cancer and COVID-19 are age-related diseases.
Aging is indexed by PubMed/Medline (abbreviated as “Aging (Albany NY)”), PubMed Central, Web of Science: Science Citation Index Expanded (abbreviated as “Aging‐US” and listed in the Cell Biology and Geriatrics & Gerontology categories), Scopus (abbreviated as “Aging” and listed in the Cell Biology and Aging categories), Biological Abstracts, BIOSIS Previews, EMBASE, META (Chan Zuckerberg Initiative) (2018-2022), and Dimensions (Digital Science).
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