Fight Aging!

Cells are each packed with hundreds of the organelles called mitochondria, the distant descendants of ancient symbiotic bacteria, constantly dividing, fusing, and passing around component parts. Mitochondria are the power plants of the cell, conducting energetic reactions to produce the chemical energy store molecule adenosine triphosphate. As a side-effect, these reactions produce a flux of oxidative molecules that can react with other cell components to damage them. This damage is constantly repaired in a healthy cell, and even acts as a hormetic signal under some circumstances. It is involved in the beneficial response to exercise, for example.

With age, however, mitochondria become less efficient and generate more oxidative molecules, putting stress on the cell. The proximate causes of this decline involves changes in gene expression relating to mitochondrial quality control (the process of mitophagy) and mitochondrial dynamics and structure, as well as damage to mitochondrial DNA. These two issues interact, in that mitochondria in a cell can become resistant to mitophagy, allowing worn and damaged organelles to accumulate. Links to the deeper causes of aging remain to be firmly established. As noted here, researchers are interested in finding ways to improve mitochondrial function in aged tissues, or at the very least soak up the harmful excess of oxidative molecules.

Targeting Mitochondrial Oxidative Stress as a Strategy to Treat Aging and Age-Related Diseases

Changes in organelle morphology or function are a characteristic of aging, among which mitochondrial degeneration is most prominent. Mitochondria exhibit structural changes such as significant increases in volume and size due to the buildup of defective mitochondria. Defective mitochondria generate reactive oxygen species (ROS) as a byproduct of electron leakage from the electron transport chain (ETC). Not only are defective mitochondria ROS generators, but they are also targets of mitochondrial oxidative stress, which then boosts mitochondrial ROS production.

Mitochondrial ROS generated by defective mitochondria deteriorate the morphology and function of organelles, consequently leading to aging and age-related diseases. Therefore, strategies to reduce mitochondrial oxidative stress may be beneficial as therapeutic approaches to aging and age-related diseases. The finding that treatment of senescent cells with ROS scavengers restored the senescent phenotype supports the usefulness of this strategy. Mitochondrial oxidative stress is a major cause of senescence and the consequent development of age-related diseases, so a deeper comprehension of the mechanisms that target and control mitochondrial oxidative stress is needed.

In this review, we investigated and discussed mitochondrial alterations and the consequent increase in mitochondrial oxidative stress. In addition, by examining the process through which mitochondrial oxidative stress progresses aging and aging-related diseases, we found that mitochondrial oxidative stress acts as a vicious feedback loop for aging. Here, we suggested mitochondrial oxidative stress as a potential target for aging. Therapeutic approaches to reduce mitochondrial oxidative stress have proven to be an important factor in treating aging and age-related diseases. However, clinical trials using non-mitochondria-targeted antioxidants have shown that non-mitochondria-targeted antioxidant therapies are not effective in the treatment of aging and age-related diseases. To complement these clinical findings, mitochondria-targeting antioxidants have recently been applied to various animal models, and there is growing evidence that mitochondria-targeting antioxidants have beneficial effects on aging and age-related diseases.