Read on the topic aging research and one will soon enough arrive at a consideration of mitochondria, their function and dysfunction. They are everywhere in the literature. These organelles are responsible for processing nutrients into chemical energy stores, and also play a role in a variety of important mechanisms in cell growth and cell death. They mediate many beneficial cellular responses to stress via generation of reactive oxygen species in greater or less amounts. Further, they are a primary target for the cellular maintenance processes of autophagy, as when mitochondria malfunction they can cause serious harm to a cell and its surroundings. That portfolio of functions and concerns is connected to all of the present methods of metabolic alteration shown to modestly slow aging in laboratory animals.
Most of these methods utilize the induction of stress response mechanisms, particular those involved in calorie restriction, the reduction of nutrient intake, which overlap with responses to exercise, to heat, to toxins, and to lack of oxygen. Altered mitochondrial function appears frequently as a central mediating mechanism. Calorie restriction itself appears to depend on increased levels of autophagy - and as soon as autophagy is involved one has to consider the reduction in mitochondrial breakage and dysfunction that results from more active mitochondrial quality control. It is even possible to tie mitochondria to the more recent efforts that depart from metabolic manipulation in order to produce rejuvenation through targeted destruction of senescent cells. Since senescent cells are primed to self-destruct, and since that process of self-destruction is mediated by mitochondria, the various pharmaceutical senolytic drug candidates target mitochondrial molecular machinery in order to force the issue.
How much of degenerative aging is mediated by mitochondria? Mitochondrial composition correlates well with species life span, suggesting importance, but that doesn't necessarily bear any relationship to the degree of harm done in any given species by the age-related failure of mitochondrial function, by the damage that accumulates in mitochondrial DNA. The only sure way to find out is to repair the damage, restore mitochondrial function, and watch what happens in a mouse study. Unfortunately, the research community is not yet capable of achieving that goal, though inroads have been made on the SENS approach of allotopic expression - copying mitochondrial DNA into the cell nucleus to prevent damage to mitochondrial genes from depriving mitochondria of necessary proteins.
In a rapidly aging society, new treatment options for age-related disorders and diseases will be increasingly important. Consequently, in recent decades, research has focused heavily on the processes of aging to reveal potential targets for prolonging health and lifespan. Consistent with this, interventions such as caloric restriction (CR) or exercise, as well as pharmacological strategies have been well established to improve health and to slow down aging.
As adenosine triphosphate (ATP)-producing power plants of the cell, mitochondria are in a unique position to influence an organism's aging process. Recent reports suggest that mitochondrial function is linked to age-associated biphasic alterations in metabolic activity, including an increase and afterwards progressive decrease in mitochondrial function. In addition, the byproducts of mitochondrial respiration, reactive oxygen species (ROS), are key determinants in the initiation of cellular senescence when present in high concentrations. Moreover, changes in mitochondrial dynamics in fusion and fission, as well as alterations in the mitochondrial membrane potential have been reported to cause cellular dysfunctions during senescence. Consequently, it seems reasonable that life-prolonging interventions, such as CR or exercise, as well as various drugs, target mitochondria.
Notably, impaired mitochondrial functions are reported to cause accelerated aging that affects primarily organs with high levels of energy demand, such as the brain, the heart, the skeletal muscle, as well as liver and kidney. The critical role of mitochondria in these organs becomes clinically visible in the case of mitochondrial diseases that frequently affect organs with high energy demand. The link between mitochondrial dysfunction and age-related diseases is well-established for Alzheimer's disease, myocardial infarction, and sarcopenia.
The process of aging evokes various alterations in mitochondrial Ca2+ handling, mitochondrial respiration, mitochondrial structure, as well as in the mitochondrial genome, which are mutually interrelated to each other. Results from cell culture and animal experiments suggest enhanced mitochondrial activity in middle age, but a decline in old age. Initially, increased activity of mitochondria might compensate for the decreased mitochondrial efficiency that occurs during aging. However, this enhanced mitochondrial activity might harm the cell long-term, for instance, by increased ROS production, and might even further promote age-related cellular dysfunction. It is of major importance to further investigate the molecular processes behind the role of mitochondria in aging, as well as their potential to serve as targets for therapeutic interventions.