Mitochondrial effectors of cellular senescence: beyond the free radical theory of aging

• Published in: Aging cell Vol. 14; no. 1; pp. 1 - 7
• Main Authors: Ziegler, Dorian V., Wiley, Christopher D., Velarde, Michael C.
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01-02-2015; BlackWell Publishing Ltd
• Subjects: Aging; Analysis; Animals; bioenergetics; Cellular Senescence; Electron Transport; electron transport chain; Free radicals; Free Radicals - metabolism; Humans; metabolism; mitochondria; Mitochondria - metabolism; Mitochondrial Dynamics; Models, Biological; NAD; reactive oxygen species; Reviews; Senescence; Theory; NAD; electron transport chain; cellular senescence; bioenergetics; mitochondria; reactive oxygen species; metabolism; aging
• ISSN: 1474-9718; 1474-9726
• DOI: 10.1111/acel.12287

Summary
Cellular senescence is a process that results from a variety of stresses, leading to a state of irreversible growth arrest. Senescent cells accumulate during aging and have been implicated in promoting a variety of age‐related diseases. Mitochondrial stress is an effective inducer of cellular senescence, but the mechanisms by which mitochondria regulate permanent cell growth arrest are largely unexplored. Here, we review some of the mitochondrial signaling pathways that participate in establishing cellular senescence. We discuss the role of mitochondrial reactive oxygen species (ROS), mitochondrial dynamics (fission and fusion), the electron transport chain (ETC), bioenergetic balance, redox state, metabolic signature, and calcium homeostasis in controlling cellular growth arrest. We emphasize that multiple mitochondrial signaling pathways, besides mitochondrial ROS, can induce cellular senescence. Together, these pathways provide a broader perspective for studying the contribution of mitochondrial stress to aging, linking mitochondrial dysfunction and aging through the process of cellular senescence.