Key Elements of Cellular Senescence

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Aging (Aging-US)

Aging-US published this research paper on May 22, 2023, in 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" by researchers from Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA; Systemic Autoimmune Diseases Research Unit, Vall d’Hebron Research Institute (VHIR), Barcelona 08035, Spain; Drug Delivery and Targeting Group, Clinical Biochemistry Department, Vall d’Hebron Hospital, Barcelona 08035, Spain; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN; Department of Physiology, Mayo Clinic, Rochester, MN; Department of Medicine, Mayo Clinic, Rochester, MN. DOI - https://doi.org/10.18632/aging.204743 Corresponding author - Renuka Kandhaya-Pillai - renugene@uw.edu Abstract 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. Seeking to understand these molecular changes, we studied the transcriptomic profiles of endothelial replication-induced senescence and senescence induced by the inflammatory cytokine, TNF-α. We 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. We 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. We show that repression of multiple target genes in the p53/p16-RB-E2F-DREAM pathway collectively contributes to the stability of the senescent arrest. Our findings show that the regulatory connection between DREAM and cellular senescence may play a potential role in the aging process. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.204743 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, cellular senescence, cell cycle, DREAM complex, DNA repair About Aging-US Launched in 2009, Aging-US publishes papers of general interest and biological significance in all fields of aging research and age-related diseases, including cancer—and now, with a special focus on COVID-19 vulnerability as an age-dependent syndrome. Topics in Aging-US go beyond traditional gerontology, including, but not limited to, cellular and molecular biology, human age-related diseases, pathology in model organisms, signal transduction pathways (e.g., p53, sirtuins, and PI-3K/AKT/mTOR, among others), and approaches to modulating these signaling pathways. Please visit our website at https://www.Aging-US.com​​ and connect with us: SoundCloud - https://soundcloud.com/Aging-Us Facebook - https://www.facebook.com/AgingUS/ Twitter - https://twitter.com/AgingJrnl Instagram - https://www.instagram.com/agingjrnl/ YouTube - https://www.youtube.com/@AgingJournal LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM