BMAL1 Modulates Senescence Programming via AP-1 | Aging-US

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Aging-US published this research paper as the cover for Volume 15, Issue 19, entitled, "BMAL1 modulates senescence programming via AP-1" by researchers from the Mayo Clinic Graduate School of Biomedical Sciences, Mayo Clinic, Rochester, MN; Robert and Arlene Kogod Center on Aging, Mayo Clinic, Rochester, MN; Epigenomics Development Laboratory, Epigenomics Program, Center for Individualized Medicine, Mayo Clinic, Rochester, MN; Department of Physiology and Biomedical Engineering, Mayo Clinic, Rochester, MN; Center for Cell Signaling in Gastroenterology, Mayo Clinic, Rochester, MN; Department of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, MN; Department of Orthopedic Surgery, Mayo Clinic, Rochester, MN; Department of Medicine, Division of Endocrinology, Metabolism, Diabetes, and Nutrition, Mayo Clinic, Rochester, MN; Department of Physical Medicine and Rehabilitation, Mayo Clinic, Rochester, MN. DOI - https://doi.org/10.18632/aging.205112 Corresponding authors - Nathan K. LeBrasseur - lebrasseur.nathan@mayo.edu Abstract Cellular senescence and circadian dysregulation are biological hallmarks of aging. Whether they are coordinately regulated has not been thoroughly studied. We hypothesize that BMAL1, a pioneer transcription factor and master regulator of the molecular circadian clock, plays a role in the senescence program. Here, we demonstrate BMAL1 is significantly upregulated in senescent cells and has altered rhythmicity compared to non-senescent cells. Through BMAL1-ChIP-seq, we show that BMAL1 is uniquely localized to genomic motifs associated with AP-1 in senescent cells. Integration of BMAL1-ChIP-seq data with RNA-seq data revealed that BMAL1 presence at AP-1 motifs is associated with active transcription. Finally, we showed that BMAL1 contributes to AP-1 transcriptional control of key features of the senescence program, including altered regulation of cell survival pathways, and confers resistance to drug-induced apoptosis. Overall, these results highlight a previously unappreciated role of the core circadian clock component BMAL1 on the molecular phenotype of senescent cells. Sign up for free Altmetric alerts about this article - https://aging.altmetric.com/details/email_updates?id=10.18632%2Faging.205112 Subscribe for free publication alerts from Aging - https://www.aging-us.com/subscribe-to-toc-alerts Keywords - aging, AP-1, circadian clock, cellular senescence, senolytic, transcription regulation 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