Adenosine triphosphate: Textbooks tell us ATP is the universal energy currency for life on Earth. In plain English, it’s how organisms get things done. In human terms, ATP is required to accomplish just about everything. From the macro level—running a marathon, for example—to the micro level—powering sodium-potassium pumps in cell membranes—ATP is what makes it all happen. And except for the small amounts of ATP created through glycolysis, the majority of ATP is generated inside mitochondria. Considering the myriad requirements for ATP throughout the body, mitochondria that malfunction or decline in number present a cellular energy crisis that, when amplified to the level of the whole body, may contribute to some of the chronic illnesses that are currently reaching epidemic levels.

A growing body of evidence now links mitochondrial dysfunction to cancer, diabetes, Alzheimer’s disease, multiple sclerosis, amyotrophic lateral sclerosis (ALS), and neurodegenerative disease in general. With this in mind, cultivating healthy mitochondria can be considered an important part of maintaining energy generation and cellular signaling from the bottom up. Fortunately, the biosynthesis of mitochondria isn’t a matter of luck or chance. Deliberate activities can lead to mitochondrial biogenesis—the building of new mitochondria. If “necessity is the mother of invention,” as the saying goes, then necessity is also the mother of functional mitochondria. If we give the body a reason to make more—impart a need for more mitochondria—the body will make them.

Exercise is one of the most effective stimulators of mitochondrial biogenesis. Animal models show that exercise and stimulation of muscle contractions increase levels of mitochondrial enzymes employed in the ATP-generating citric acid cycle and fatty acid oxidation pathways, resulting in proportional increases in cells’ capacity to oxidize fuel substrates and generate ATP through the mitochondrial electron transport chain.

High intensity training seems to be especially beneficial for strengthening mitochondria. In a study of young males doing interval training involving one-legged cycling (to isolate findings to the exercising muscles only), just two weeks of high-intensity activity led to increases in mitochondrial function in skeletal muscle. An interesting finding to note is that these beneficial changes were independent of detectable increases in mitochondrial synthesis. This suggests that the bouts of exercise made existing mitochondria more effective at generating higher amounts of ATP, rather than this being a result of an increase in the total number of mitochondria.

The benefits of exercise on mitochondrial biogenesis and maintenance aren’t limited to the skeletal muscles actually performing the work. Animal studies have shown that exercise can induce the generation of new mitochondria even in the brain. This could be a boon for addressing age-related dementia and other forms of cognitive decline and impairment. Researchers speculate that brain mitochondrial biogenesis might be a two-way street: exercise leads to synthesis of new mitochondria, and the resulting improvements in brain mitochondrial respiratory capacity may lead to increased exercise endurance. Reaching exhaustion may not be solely the result of physical fatigue. With the brain being such an energy-hungry organ, with constant requirements for high amounts of ATP, “hitting the wall” may be due to central fatigue as well as physical exhaustion. Central fatigue is “the progressive reduction in voluntary drive to motor neurons during exercise, which can include both mental and physical factors. Decreases in cerebral metabolic ratio, impaired oxygenation, reduced central motor drive, altered neurotransmission, and impaired mood state have all been implicated in the development of centrally mediated fatigue.” Thus, increasing brain mitochondrial capacity might increase physical endurance capacity, too.

It is possible to get too much of a good, thing, however. Like many things that support good health, exercise has a U-shaped curve. That is, too little isn’t good, but too much can be harmful. Some is helpful; more isn’t always better. Appropriate levels of exercise promote health, but over-training can have the opposite effect. Too much exercise—whether in volume, intensity, or frequency—without adequate rest, recovery, and nutrient replenishment—can lead to levels of oxidative stress that overwhelm the body’s capacity to repair and regenerate.

When it comes to mitochondrial function, a good rule of thumb might be: “Use ‘em or lose ‘em, but don’t abuse ‘em!”