The Relevance of Mitochondrial Metabolism to Cellular Senescence

It is plausible that the mitochondrial dysfunction characteristic of aging increases the pace at which cells become senescent, and harms the efforts of immune cells to remove senescent cells. With age, the burden of senescent cells rises in tissues throughout the body. This is likely an imbalance between the pace of creation and pace of destruction. Regardless, when even a small fraction of the cells in a tissue are senescent, the inflammatory signals they produce become disruptive of tissue function and structure. The open access review here is more focused on the question of how mitochondrial function is changed as a result of the senescent state, however, and whether targeting mitochondrial function can be of benefit, such as by suppressing some of the more harmful aspects of senescence.

Mitochondria are one of organelles that undergo significant changes associated with senescence. An increase in mitochondrial size is observed in senescent cells, and this increase is ascribed to the accumulation of dysfunctional mitochondria that generate excessive reactive oxygen species (ROS). Such dysfunctional mitochondria are prime targets for ROS-induced damage, which leads to the deterioration of oxidative phosphorylation and increased dependence on glycolysis as an energy source. Based on findings indicating that senescent cells exhibit mitochondrial metabolic alterations, a strategy to induce mitochondrial metabolic reprogramming has been proposed to treat aging and age-related diseases.

In this review, we discuss senescence-related mitochondrial changes and consequent mitochondrial metabolic alterations. We assess the significance of mitochondrial metabolic reprogramming for senescence regulation and propose the appropriate control of mitochondrial metabolism to ameliorate senescence. Learning how to regulate mitochondrial metabolism will provide knowledge for the control of aging and age-related pathologies. Further research focusing on mitochondrial metabolic reprogramming will be an important guide for the development of anti-aging therapies, and will provide novel strategies for anti-aging interventions.


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