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REVIEW article

Front. Pharmacol.
Sec. Experimental Pharmacology and Drug Discovery
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1486717
This article is part of the Research Topic Targeting Mitochondria in Aging and Disease View all 7 articles

The Role of CYP-sEH Derived Lipid Mediators in Regulating Mitochondrial Biology and Cellular Senescence: Implications for the Aging Heart

Provisionally accepted
Ala Yousef Ala Yousef Liye Fang Liye Fang Mobina Heidari Mobina Heidari Joshua Kranrod Joshua Kranrod John M. Seubert John M. Seubert *
  • Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, Alberta, Canada

The final, formatted version of the article will be published soon.

    Cellular senescence is a condition characterized by stable, irreversible cell cycle arrest linked to the aging process. The accumulation of senescent cells in the cardiac muscle can contribute to various cardiovascular diseases (CVD). Telomere shortening, epigenetic modifications, DNA damage, mitochondrial dysfunction, and oxidative stress are known contributors to the onset of cellular senescence in the heart. The link between mitochondrial processes and cellular senescence contributed to the age-related decline in cardiac function. These include changes in mitochondrial functions and behaviours that arise from various factors, including impaired dynamics, dysregulated biogenesis, mitophagy, mitochondrial DNA (mtDNA), reduced respiratory capacity, and mitochondrial structural changes. Thus, regulation of mitochondrial biology has a role in cellular senescence and cardiac function in aging hearts. Targeting senescent cells may provide a novel therapeutic approach for treating and preventing CVD associated with aging. CYP epoxygenases metabolize N-3 and N-6 polyunsaturated fatty acids (PUFA) into epoxylipids that are readily hydrolyzed to diol products by soluble epoxide hydrolase (sEH). Increasing epoxylipids levels or inhibition of sEH has demonstrated protective effects in the aging heart. Evidence suggests they may play a role in cellular senescence by regulating mitochondria, thus reducing adverse effects of aging in the heart. In this review, we discuss how mitochondria induce cellular senescence and how epoxylipids affect the senescence process in the aged heart.

    Keywords: Mitochondria, Aging, PUFA, CYP, Soluble epoxide hydrolase (sEH), epoxylipids

    Received: 26 Aug 2024; Accepted: 28 Oct 2024.

    Copyright: © 2024 Yousef, Fang, Heidari, Kranrod and Seubert. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: John M. Seubert, Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, T6G 2N8, Alberta, Canada

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.