Department of Physiology, Faculty of Nursing and Occupational Therapy, University of Extremadura, Cáceres, Spain.
J Pineal Res. 2014 Mar;56(2):163-74. doi: 10.1111/jpi.12109. Epub 2013 Dec 26.
Aging is a multifactorial process that involves biochemical, structural, and functional changes in mitochondria. The ability of melatonin to palliate the alterations induced by aging is based on its chronobiologic, antioxidant, and mitochondrial effects. There is little information about the effects of melatonin on the in situ mitochondrial network of aging cells and its physiological implications. We have studied the ability of melatonin to prevent the functional alterations of in situ mitochondria of smooth muscle cells and its impact on contractility. Mitochondrial membrane potential was recorded in isolated colonic smooth muscle cells from young mice (3 month old), aged mice (22-24-month old), and aged mice treated with melatonin (starting at 14-month age). Aging induced a partial mitochondrial depolarization in resting conditions and reduced the depolarizing response to cellular stimulation. Use of oligomycin indicated that aging enhanced the resting activity of the mitochondrial ATP synthase, whereas in young cells, the enzyme operated mainly in reverse mode. Melatonin treatment prevented all these changes. Aging reduced both spontaneous and stimulated contraction of colonic strips and shifted the metabolic dependence of contraction from mitochondria to glycolysis, as indicated the use of mitochondrial and glycolysis inhibitors. These functional alterations were also palliated by melatonin treatment. Aging effects were not related to a decrease in Ca2+ store mobilization, because this was enhanced in aged cells and restored by melatonin. In conclusion, melatonin prevents the age induced in situ mitochondrial potential alterations in smooth muscle cells and the associated changes in contractility and metabolism.
衰老是一个涉及到生化、结构和功能变化的多因素过程。褪黑素缓解衰老引起的变化的能力基于其生物钟、抗氧化和线粒体效应。关于褪黑素对衰老细胞原位线粒体网络的影响及其生理意义的信息很少。我们研究了褪黑素预防平滑肌细胞原位线粒体功能改变的能力及其对收缩性的影响。在年轻小鼠（3 月龄）、老年小鼠（22-24 月龄）和用褪黑素治疗的老年小鼠（从 14 月龄开始）的分离结肠平滑肌细胞中记录线粒体膜电位。衰老导致静息状态下线粒体部分去极化，并降低了细胞刺激的去极化反应。使用寡霉素表明，衰老增强了线粒体 ATP 合酶的静息活性，而在年轻细胞中，该酶主要以反转模式运行。褪黑素治疗可预防所有这些变化。衰老降低了结肠带的自发性和刺激收缩，并将收缩的代谢依赖性从线粒体转移到糖酵解，这表明使用线粒体和糖酵解抑制剂。褪黑素治疗也缓解了这些功能改变。衰老效应与 Ca2+储存动员减少无关，因为在衰老细胞中增强了 Ca2+储存动员，并且褪黑素可以恢复其水平。总之，褪黑素可预防平滑肌细胞原位线粒体电位改变以及相关的收缩性和代谢变化。
