For many, exercise is a means to an end, which is better health – and in a perfect world there may be a way to skip that middle step with some kind of pill or injection. Now, scientists at the University of Southern California (USC) have studied a hormone released by the human body during exercise and found that giving it to mice improves fitness and overall health.
The hormone in question is called MOTS-c, and its role in exercise was identified a few years ago by the same researchers in a similar study in mice. One of the unusual features of MOTS-c is that it is not encoded by the main genome in our cells, but rather by the mitochondria, which have their own smaller genome.
“Mitochondria are known to be the cell’s energy source, but they are also nodes that coordinate and optimize metabolism by actively communicating with the rest of the body,” says Changhan David Lee, corresponding author of the study. “As you get older, this communications network seems to break down, but our study suggests that you can restore that network or rejuvenate an older mouse to be as fit as a younger one.”
In the new study, USC scientists looked at MOTS-c in both humans and mice. The team had 10 healthy (but sedentary) male volunteers aged 20 who exercised on a stationary bike and then rested for four hours. The researchers took samples of their skeletal muscle and plasma to measure MOTS-c levels before, during, and after exercise, and after the rest of the workout.
Sure enough, the team found that skeletal muscle MOTS-c levels increased significantly by 11.9 times after exercise, and although they went back to baseline over time, levels were still after the four-hour break higher than before. MOTS-c in the plasma was also increased by 50 percent after training and fell to the baseline value more quickly.
With that in mind, the team next examined the hypothesis that exercise triggers the release of MOTS-c, and that the hormone itself is responsible for some of the physical benefits associated with exercise. The researchers injected MOTS-c into mice of different ages – two-month-old young mice, 12-month-old middle-aged mice, and 22-month-old older mice – for two weeks, and then allowed them to perform physical challenges.
In all age groups, the treated mice performed significantly better than controls when tested on a rotating stick and treadmill. Interestingly, the older mice appeared to be rejuvenated from the treatment, which improved their grip strength, gait and walking ability.
“The older mice were the human equivalent of 65 and above and after treatment they doubled their running capacity on the treadmill,” says Lee. “They even managed to escape their untreated middle-aged cohorts.”
In a follow-up experiment, the team investigated how MOTS-c treatment affected mice under metabolic stress. The mice were given a high-fat diet which was then treated with MOTS-c at various doses twice daily. After seven days of treatment, the animals had improved insulin sensitivity, which reduced their risk of diabetes. The animals also gained less weight than untreated mice as a result of the high-fat diet.
After 10 days, mice with the higher dose of MOTS-c continued to run and burned more energy than untreated ones. In fact, 100 percent of the higher dose mice could complete the final treadmill test – sprinting 23 m (75 ft) per minute – while only 16.6 percent of the mice in the lower dose and control groups managed the feat.
While there is still much work to be done before this can be adapted to human treatment, the results are encouraging. In particular, it could help older people stay healthier longer.
“Indicators of physical decline in humans, such as For example, reduced stride length or the ability to walk are strongly related to mortality and morbidity, ”says Lee. “Interventions against age-related decline and frailty that are applied later in life would be translationally more practical compared to lifelong treatments.”
The research was published in the journal Nature Communications. The team describes the work in the following video.
Watch them run: ‘Exercise Protein’ doubles running capacity and extends the healthy lifespan of old mice
Source: University of Southern California