Scientists have identified a hormone that is generated during exercise, and they determined that when mice are treated with this powerful hormone, their physical performance and fitness is improved. This study has provided new insights into how the mitochondrial genome, which is found only in mitochondria and not in the nucleus with the rest of the genome, is involved in the regulation of physical capacity and metabolism during aging. The researchers suggested that this work, which has been reported in Nature Communications, can help us learn more about addressing the physical decline that accompanies age.
"Mitochondria are known as the cell's energy source, but they are also hubs that coordinate and fine-tune metabolism by actively communicating to the rest of the body," said corresponding study author Changhan David Lee, assistant professor at the USC Leonard Davis School of Gerontology. "As we age, that communication network seems to break down, but our study suggests you can restore that network or rejuvenate an older mouse so it is as fit as a younger one."
MOTS-c is one of several hormones that have been recently identified and found to mimic the effects of exercise. But MOTS-c is not like other proteins; its code is found in the mitochondrial genome.
In this work, the researchers injected mice of varying ages with MOTS-c and took measurements of their physical capacity and performance. They found that mice of any age that received MOTS-c were significantly better than their untreated counterparts at physical challenges like balancing and running. When the experiment was repeated with mice that were fed a high-fat diet, MOTS-c still improved performance and the treated mice gained less weight than untreated mice.
While mice of any age did better when they were given MOTS-c, significant improvements were seen in the oldest mice. Their grip strength, stride length, and physical performance all improved.
"The older mice were the human equivalent of 65 and above and once treated, they doubled their running capacity on the treadmill," Lee said. "They were even able to outrun their middle-aged, untreated cohorts."
The researchers also collected samples of skeletal muscle tissue and plasma from human volunteers who were healthy but sedentary. These samples were obtained before, during, and after the volunteers did some exercise on a stationary bicycle. The scientists found that after that exercise, MOTS-c levels were increased 12-fold in the participants' muscle cells and were still elevated four hours later. MOTS-c levels in the blood were also increased, but by about 50 percent during and after exercise; they returned to baseline after a four-hour rest.
This work adds evidence to the idea that both the nuclear and mitochondrial genome are involved in the aging process.
Though more work will be needed, it may one day be possible to stave off the effects of aging or increase health span with MOTS-c , Lee suggested.
"Indicators of physical decline in humans, such as reduced stride length or walking capacity, are strongly linked to mortality and morbidity," he noted. "Interventions targeting age-related decline and frailty that are applied later in life would be more translationally feasible compared to lifelong treatments."