Mitochondrial Stress Signaling in Longevity
Mitochondria are the power plants of the cell, a bacteria-like herd of organelles that have an important role in aging. They become damaged as a result of their everyday activities, and that damage ultimately creates malfunctioning cells that harm surrounding tissues. Many of the methods demonstrated to slow aging in laboratory animals involve alterations to mitochondrial function that may impact the pace at which their damage progresses or degree to which it is ameliorated by cellular housekeeping mechanisms. We would like to see a comprehensive way to entirely eliminate this damage, however, a way to completely repair mitochondrial damage and reset the clock on this contribution to degenerative aging. Fortunately there are a range of possible approaches to this goal, such as replacement of mitochondria, replacement of their DNA, moving their DNA into the cell nucleus, and so forth.
This open access paper covers what is known of the numerous ways in which mitochondria are thought to influence the behavior of other important biological systems also linked to aging:
Mitochondria are principal regulators of cellular function and metabolism. In addition, mitochondria play a key role in cell signaling through production of reactive oxygen species that modulate redox signaling. Recent findings support an additional mechanism for control of cellular and tissue function by mitochondria through complex mitochondrial-nuclear communication mechanisms and potentially through extracellular release of mitochondrial components that can act as signaling molecules. The activation of stress responses including mitophagy, mitochondrial number, fission and fusion events, and the mitochondrial unfolded protein response requires mitochondrial-nuclear communication for the transcriptional activation of nuclear genes involved in mitochondrial quality control and metabolism.The induction of these signaling pathways is a shared feature in long-lived organisms spanning from yeast to mice. As a result, the role of mitochondrial stress signaling in longevity has been expansively studied. Current and exciting studies provide evidence that mitochondria can also signal among tissues to up-regulate cytoprotective activities to promote healthy aging. Alternatively, mitochondria release signals to modulate innate immunity and systemic inflammatory responses and could consequently promote inflammation during aging. In this review, established and emerging models of mitochondrial stress response pathways and their potential role in modulating longevity are discussed.