Trending With Impact: Cellular Senescence Alleviated Using Oxazoloquinoline Analog

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February 2, 2022

Aging (Aging-US) published this research paper as the cover for Volume 14, Issue 2, entitled, "Targeting regulation of ATP synthase 5 alpha/beta dimerization alleviates senescence" by researchers from the Division of Life Sciences, College of Life Sciences and Bioengineering, Incheon National University, Incheon 22012, Korea; College of Pharmacy, Korea University, Sejong 30019, Republic of Korea. DOI - https://doi.org/10.18632/aging.203858 Correspondence to - Youngjoo Byun - yjbyun1@korea.ac.kr and Joon Tae Park - joontae.park@inu.ac.kr Abstract: Senescence is a distinct set of changes in the senescence-associated secretory phenotype (SASP) and leads to aging and age-related diseases. Here, we screened compounds that could ameliorate senescence and identified an oxazoloquinoline analog (KB1541) designed to inhibit IL-33 signaling pathway. To elucidate the mechanism of action of KB1541, the proteins binding to KB1541 were investigated, and an interaction between KB1541 and 14–3–3ζ protein was found. Specifically, KB1541 interacted with 14–3–3ζ protein and phosphorylated of 14–3–3ζ protein at serine 58 residue. This phosphorylation increased ATP synthase 5 alpha/beta dimerization, which in turn promoted ATP production through increased oxidative phosphorylation (OXPHOS) efficiency. Then, the increased OXPHOS efficiency induced the recovery of mitochondrial function, coupled with senescence alleviation. Taken together, our results demonstrate a mechanism by which senescence is regulated by ATP synthase 5 alpha/beta dimerization upon fine-tuning of KB1541-mediated 14–3–3ζ protein activity. Sign up for free Altmetric alerts about this article - https://oncotarget.altmetric.com/details/email_updates?id=10.18632%2Foncotarget.203858 Keywords - aging, senescence amelioration, KB1541, ATPase synthase 5, OXPHOS 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 http://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/agingus​ LinkedIn - https://www.linkedin.com/company/aging/ Pinterest - https://www.pinterest.com/AgingUS/ Aging-US is published by Impact Journals, LLC: http://www.ImpactJournals.com​​ Media Contact 18009220957 MEDIA@IMPACTJOURNALS.COM

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