Exercise is good for the body and mind, reducing stress, boosting physical fitness and even helping to alleviate certain medical problems. But as we get older or experience certain long-term illnesses, our tolerance to exercise often decreases, fostering inactivity and thus associated declines in heart and metabolic health.

Encouragingly, a new study has suggested that in the future, it might be possible to reduce exercise fatigue and thus allow people to glean its beneficial effects, something that has become of increased importance in light of our aging population. As described in Cell Metabolism, scientists from Duke University have detailed an enzyme system that provides muscles with access to energy reserves during exercise, thus optimizing energy use.

Importantly, dietary supplementation with a substance that boosts the activity of this system allowed mice to exercise for longer, but the researchers caution that it’s far too early to extrapolate this data for humans.

The enzyme at the center of this system is called cartinine acetyltransferase (CrAT), which is located in our cell’s tiny, sausage-shaped powerhouses, the mitochondria. CrAT’s job in energy metabolism is to catalyze the reversible exchange of fatty acid groups between the metabolic molecules coenzyme A and cartinine, facilitating the production or breakdown of a molecule called acetylcartinine. While this much was known, its role in exercise was unclear.

To find out more, the team genetically engineered mice to lack the gene for CrAT, but only in skeletal muscle. The team then examined their performance on a tiny treadmill when compared with normal mice, which revealed that the CrAT deficient mice tired much faster than the controls during exercise, regardless of the type of exercise test they were enduring. This led the researchers to conclude that when muscles start to reach exhaustion, they begin to use acetylcartenine as a resource for the molecules needed to fuel energy-making reactions.

To examine the possibility of enhancing this process by increasing the availability of acetylcartenine, the researchers added it to muscle tissue isolated from the limbs of mice and then stimulated them to examine how long it took to reach fatigue. Tissue from control mice took longer to tire out when given acetylcartenine, but no effect was observed in samples lacking the CrAT gene.

Taking this one step further, the scientists then added cartenine supplements to the diets of both control and CrAT-deficient mice over a 4-week period. As anticipated, exercise tolerance increased in the control mice, but not the genetically engineered animals. All in all, the results suggest that activity of the CrAT system is needed for optimal exercise performance.   

Although we can’t genetically engineer people to be CrAT-deficient to demonstrate the same effects in humans, the researchers were able to gain support for their findings by discovering that individuals who exercise a lot possess more CrAT in their muscles than controls. However, despite what they found in mice, it’s still too early to tell whether cartenine supplementation can exert the same beneficial effects in humans.

“This work is not meant to imply that everyone should be taking cartenine supplements,” senior author Deborah Muoio said in a statement. “We need to consider underlying genetics, lifestyle factors and acquired conditions.”