Yousef Ala, Fang Liye, Heidari Mobina, Kranrod Joshua, Seubert John M
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada.
Department of Pharmacology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB, Canada.
Front Pharmacol. 2024 Dec 5;15:1486717. doi: 10.3389/fphar.2024.1486717. eCollection 2024.
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.
细胞衰老一种以与衰老过程相关的稳定、不可逆细胞周期停滞为特征的状态。心肌中衰老细胞的积累会导致各种心血管疾病（CVD）。端粒缩短、表观遗传修饰、DNA损伤、线粒体功能障碍和氧化应激是已知的心脏细胞衰老发生的促成因素。线粒体过程与细胞衰老之间的联系导致了与年龄相关的心脏功能下降。这些包括由各种因素引起的线粒体功能和行为的变化，包括动力学受损、生物发生失调、线粒体自噬、线粒体DNA（mtDNA）、呼吸能力降低和线粒体结构变化。因此，线粒体生物学的调节在衰老心脏的细胞衰老和心脏功能中起作用。靶向衰老细胞可能为治疗和预防与衰老相关的心血管疾病提供一种新的治疗方法。细胞色素P450环氧化酶将N-3和N-6多不饱和脂肪酸（PUFA）代谢为环氧脂质，这些环氧脂质很容易被可溶性环氧化物水解酶（sEH）水解为二醇产物。增加环氧脂质水平或抑制sEH已在衰老心脏中显示出保护作用。有证据表明，它们可能通过调节线粒体在细胞衰老中发挥作用，从而减少心脏衰老的不利影响。在这篇综述中，我们讨论了线粒体如何诱导细胞衰老以及环氧脂质如何影响老年心脏的衰老过程。
