Longevity Briefs: Time-Restricted Feeding Reshapes Mitochondria In Muscle Tissue

Longevity briefs provides a short summary of novel research in biology, medicine, or biotechnology that caught the attention of our researchers in Oxford, due to its potential to improve our health, wellbeing, and longevity.

The problem:

Fasting and calorie restriction (a sharp reduction in calorie intake without causing malnutrition) have both been shown to significantly extend lifespan in animal models. Regardless of whether this also applies to humans, there are many reasons to believe that dietary practices like fasting are beneficial to human health and could help delay age-related diseases. One notable concern with fasting is that it might lead to muscle loss, which becomes increasingly problematic with advancing age. Older adults often fail to consume sufficient protein in their diets, which may be exacerbated by fasting, resulting in increased breakdown of muscle tissue to make up the shortfall. Sarcopenia, the age-related loss of muscle mass, is a significant cause of falls, fractures and reduced quality of life among the elderly.

On the other hand, muscle function isn’t just about quantity but also quality. In this respect, problems begin during middle age as the mitochondria (the ‘power plants’ of the cell) start to become less efficient due to the accumulation of damage at a molecular level. Fasting and other forms of calorie restriction may benefit mitochondrial health in a variety of ways, such as promoting the destruction of damaged mitochondria and enhancing the production of new ones. In this study, researchers investigate the effects of time-restricted feeding (TRF, where food intake is confined to a defined daily time window) on ‘middle aged’ mice, including the effects on mitochondria within their muscle tissue.

The discovery:

The researchers took twenty-six 10-month-old mice (‘equivalent’ to early middle age) and assigned them to either a control group with unrestricted food access, or to a TRF group that could only eat during a 12-hour window that overlapped with their inactive (sleeping) phase. TRF lasted for 8 weeks, after which time researchers performed various measurements including grip strength as a measure of muscle function.

They found that body weight was not significantly impacted by TRF, nor was the mice’s ability to control blood sugar after a sugar-rich meal, though control mice had slightly higher blood sugar in a fasted state. Control mice with unrestricted food access showed a statistically significant decline in both maximum and average (mean) grip strength after the 8 week period, whereas there was no statistically significant change in either metric among the TRF mice.

Researchers then examined muscle tissue samples from mice to see if there were differences in muscle structure that could explain improved performance in TRF mice. They found that the molecular effects were different for ‘fast twitch’ and ‘slow twitch’ muscle fibres, which are recruited for short-burst exercise and endurance exercise respectively. In fast twitch fibres, mitochondria became larger, while in slow twitch fibres they became smaller and more numerous. These differences in response are probably related to the different energy demands of these fibres, where fast twitch fibres are optimised for short-term anaerobic respiration, while slow twitch fibres are able to maintain long-term aerobic respiration).

The implications:

This research suggests that, at least in mice, TRF leads to fibre-specific changes in mitochondrial size and distribution that might contribute to preserving muscle function in middle age. According to the authors, only one other study had previously shown similar effects on muscle tissue mitochondria in response to calorie restriction, so this is a relatively new line of research. As a form of calorie restriction, TRF is often easier for people to achieve because it doesn’t involve calorie counting or very prolonged periods without eating.

TRF might help people in middle age delay the cellular-level decline that will eventually lead to sarcopenia later in life, but much more work needs to be done to fully understand the benefits and risks of all forms of calorie restriction in humans. There are many variables that could influence how people respond to calorie restriction, including age, diet and physical activity. Current evidence suggests that on average, long-term calorie restriction does lead to a small loss of muscle mass, but that the remaining muscle functions better, resulting in no overall loss of strength.