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Mitochondrial dysfunction in cell senescence and aging
Satomi Miwa, … , Eduardo Chini, Thomas von Zglinicki
Satomi Miwa, … , Eduardo Chini, Thomas von Zglinicki
Published July 1, 2022
Citation Information: J Clin Invest. 2022;132(13):e158447. https://doi.org/10.1172/JCI158447.
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Review Series

Mitochondrial dysfunction in cell senescence and aging

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Abstract

Mitochondrial dysfunction and cell senescence are hallmarks of aging and are closely interconnected. Mitochondrial dysfunction, operationally defined as a decreased respiratory capacity per mitochondrion together with a decreased mitochondrial membrane potential, typically accompanied by increased production of oxygen free radicals, is a cause and a consequence of cellular senescence and figures prominently in multiple feedback loops that induce and maintain the senescent phenotype. Here, we summarize pathways that cause mitochondrial dysfunction in senescence and aging and discuss the major consequences of mitochondrial dysfunction and how these consequences contribute to senescence and aging. We also highlight the potential of senescence-associated mitochondrial dysfunction as an antiaging and antisenescence intervention target, proposing the combination of multiple interventions converging onto mitochondrial dysfunction as novel, potent senolytics.

Authors

Satomi Miwa, Sonu Kashyap, Eduardo Chini, Thomas von Zglinicki

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Figure 1

Mitochondrial dysfunction in senescence.

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Mitochondrial dysfunction in senescence.
Illustrations are representativ...
Illustrations are representative of mitochondrial mass, membrane potential, and ROS levels in young versus senescent fibroblasts as observed after staining with fluorescent dyes. Mitochondria in human fibroblasts can be stained with MitoTracker (green) to show mitochondrial mass and tetramethylrhodamine methyl ester (TMRM) (red), which accumulates in mitochondria in a membrane potential–dependent fashion at under-saturated concentrations. There is higher mitochondrial mass in senescent fibroblasts, but their membrane potential is lower (as indicated by weak and patchy TMRM staining) than in non-senescent (young) fibroblasts. The mitochondrial network is more fragmented in young cells, while mitochondria are fused in senescence. Mitochondrial superoxide levels can be visualized using MitoSOX (pink). Mitochondrial superoxide levels are elevated in senescent human fibroblasts.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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