Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas.
Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology-Hellas; Department of Basic Sciences, Medical School, University of Crete, Heraklion, Greece.
Int Rev Cell Mol Biol. 2018;340:169-208. doi: 10.1016/bs.ircmb.2018.05.005. Epub 2018 Jun 20.
Aging is a complex biological process affecting almost all living organisms. Although its detrimental effects on animals' physiology have been extensively documented, several aspects of the biology of aging are insufficiently understood. Mitochondria, the central energy producers of the cell, play vital roles in a wide range of cellular processes, including regulation of bioenergetics, calcium signaling, metabolic responses, and cell death, among others. Thus, proper mitochondrial function is a prerequisite for the maintenance of cellular and organismal homeostasis. Several mitochondrial quality control mechanisms have evolved to allow adaptation to different metabolic conditions, thereby preserving cellular homeostasis and survival. A tight coordination between mitochondrial biogenesis and mitochondrial selective autophagy, known as mitophagy, is a common characteristic of healthy biological systems. The balanced interplay between these two opposing cellular processes dictates stress resistance, healthspan, and lifespan extension. Mitochondrial biogenesis and mitophagy efficiency decline with age, leading to progressive accumulation of damaged and/or unwanted mitochondria, deterioration of cellular function, and ultimately death. Several regulatory factors that contribute to energy homeostasis have been implicated in the development and progression of many pathological conditions, such as neurodegenerative, metabolic, and cardiovascular disorders, among others. Therefore, mitophagy modulation may serve as a novel potential therapeutic approach to tackle age-associated pathologies. Here, we review the molecular signaling pathways that regulate and coordinate mitophagy with mitochondrial biogenesis, highlighting critical factors that hold promise for the development of pharmacological interventions toward enhancing human health and quality of life throughout aging.
衰老是一个影响几乎所有生物体的复杂生物学过程。尽管其对动物生理学的有害影响已被广泛记录，但衰老生物学的几个方面仍未被充分理解。线粒体是细胞的主要能量产生器，在多种细胞过程中发挥着至关重要的作用，包括调节生物能量学、钙信号传递、代谢反应和细胞死亡等。因此，适当的线粒体功能是维持细胞和机体稳态的前提。已经进化出几种线粒体质量控制机制，以适应不同的代谢条件，从而保持细胞稳态和生存。线粒体生物发生和线粒体选择性自噬（即自噬）之间的紧密协调是健康生物系统的共同特征。这两种相反的细胞过程之间的平衡相互作用决定了应激抗性、健康寿命和寿命延长。线粒体生物发生和自噬效率随年龄增长而下降，导致受损和/或不需要的线粒体逐渐积累、细胞功能恶化，最终导致死亡。许多调节能量稳态的调节因子被牵连到许多病理状况的发展和进展中，如神经退行性疾病、代谢和心血管疾病等。因此，自噬调节可能成为一种新的潜在治疗方法，以解决与年龄相关的病理。在这里，我们综述了调节线粒体生物发生和自噬的分子信号通路，强调了一些关键因素，这些因素有望为开发药物干预措施提供新的思路，以提高人类在衰老过程中的健康和生活质量。
