Clinico-Molecular Biochemistry Laboratory, Department of Biochemistry, Faculty of Sciences, University of Agriculture, Faisalabad, Pakistan.
Clinico-Molecular Biochemistry Laboratory, Department of Biochemistry, Faculty of Sciences, University of Agriculture, Faisalabad, Pakistan.
Adv Protein Chem Struct Biol. 2023;136:93-115. doi: 10.1016/bs.apcsb.2023.03.001. Epub 2023 Mar 28.
Mitochondrial malfunction and cell senescence have been defined as the hallmarks of aging. Cell senescence leads to the loss of health allied with aging. While deciphering the complex association between mitochondria and cellular senescence, it is observed that senescence has a two-faced nature being beneficial and hazardous. This duality of cellular senescence is associated with circumstantial aspects. During the process of cellular senescence, dysfunctional mitochondria are accumulated, the efficiency of the oxidative phosphorylation process declines along with the enhanced synthesis of reactive oxygen species. It is suggested that reduction in the negative consequences of senescence throughout old age might be accomplished by targeting the mitochondria as all roads lead towards mitochondria. It is unclear how perturbation of mitophagy in senescence results in the accumulation of mitochondria, impairment of mitochondrial biogenesis and onset of diseases. Understanding this complex interplay will bring about a long yet healthy lifespan. But definitely casual and specific players contribute in the initiation and conservation of the cell senescence. Variations in metabolism, quality control and dynamics of mitochondria are observed during cell aging process. Several On-target and Off-target mechanisms can also cause side effects in cellular senescence. Translational research of these mechanisms may lead to effective clinical interventions. This chapter reviews the role of mitochondria, homeostatic mechanisms and mitophagy as drivers and effectors of cell senescence along with multiple signalling pathways that lead to the initiation, maintenance, induction and suppression of cellular aging process during health and disease.
线粒体功能障碍和细胞衰老被定义为衰老的标志。细胞衰老导致与衰老相关的健康丧失。在破译线粒体和细胞衰老之间复杂的关联时,观察到衰老具有两面性,既有好处也有危害。这种细胞衰老的双重性与环境因素有关。在细胞衰老过程中,功能失调的线粒体积累,氧化磷酸化过程的效率下降,同时活性氧的合成增强。有人认为,通过靶向线粒体来减少衰老的负面影响可能会随着所有的道路都通向线粒体而实现。目前还不清楚在衰老过程中,自噬作用的失调如何导致线粒体的积累、线粒体生物发生的损害以及疾病的发生。了解这种复杂的相互作用将带来更长但健康的寿命。但是,肯定有一些偶然和特定的因素参与了细胞衰老的启动和维持。在细胞衰老过程中观察到代谢、质量控制和线粒体动力学的变化。几种靶向和非靶向机制也可能导致细胞衰老的副作用。对这些机制的转化研究可能会导致有效的临床干预。本章综述了线粒体、内稳态机制和自噬作为细胞衰老的驱动因素和效应因子的作用,以及在健康和疾病过程中导致细胞衰老过程的启动、维持、诱导和抑制的多种信号通路。