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New insights into age-related muscle decline

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6 February 2025
Physiologist Richie Goulding of VU Amsterdam discovered that as we age, the mitochondria - structures inside our muscle cells that provide the energy needed for movement - become fragmented and less efficient. This leads to a decline in exercise performance. Understanding these changes could help develop ways to preserve muscle energy as we age.

As we age, staying active becomes harder, but new research by physiologist Richie Goulding may explain why our muscles cannot provide the same energy as before. “We wanted to further understand the processes behind the decline of our physical capacity.”

To do so, Goulding focused on mitochondria, structures inside our muscle cells that provide energy needed for movement. They are also known as the cell's powerhouses. They are highly abundant in the muscles connected to our bones. “They are responsible for generating energy for muscle contraction,” Goulding explains. He wanted to investigate the role of mitochondria in diminishing exercise capacity with age. His conclusions have now been published in the journal Aging Cell.

Comparing

“To investigate this, we compared young (around 27 years of age) and middle-aged (around 55) individuals. The groups had a similar level of physical activity, allowing us to attribute group differences to age per se, rather than the reduced physical activity that often accompanies ageing”, says Goulding. All subjects did a cycling test to measure their fitness, while a non-invasive probe tracked how much oxygen their muscles used. Subjects also underwent a muscle biopsy, so that the researchers could analyse these muscle samples and compare the mitochondria.

Changes

Goulding and colleagues did not find any differences in the total amount of mitochondria, which is typical at older age. However, in middle-aged individuals, the mitochondria were smaller and more numerous. Goulding: “This implies that the mitochondria in their muscles were more fragmented. This suggests that mitochondrial fragmentation could be an early marker of ageing in muscles, possibly occurring before the total amount of mitochondria declines with age.” Since muscles rely on a well-connected network to produce and distribute energy efficiently, this fragmentation may reduce energy supply and make it harder to sustain exercise. Targeting this fragmentation may offer a way to slow down or prevent age-related muscle decline.

Goulding also noticed a change when it comes to a specific type of mitochondria that are located near tiny blood vessels and help pull oxygen from the bloodstream into the muscle. “In middle-aged individuals, there were fewer of these mitochondria, which might explain why older muscles struggle to get enough oxygen during exercise,” Goulding tells us.

Lastly, Goulding found changes at the level of the individual mitochondrion. Goulding: “In older individuals, the inner folds of these structures, called cristae, were less dense. These folds are important because they hold the enzymes that help generate energy. If they do not work properly, muscle cells may produce less energy.”

In conclusion, the structural changes in mitochondria were directly linked to lower exercise capacity in middle-aged individuals. “These changes were enough to explain up to 87% of the differences in physical performance between younger and middle-aged people”, Goulding says.

Further steps

Since the older group was very fit for their age, their muscles did not yet display the typical signs of ageing, such as reduced muscle size. But their muscles did show signs of ageing at a mitochondrial level. “This suggests targeting changes in the mitochondria could be a promising way to slow or prevent muscle decline as we age.”

While we may not have all the answers yet, this research opens up exciting possibilities for maintaining muscle strength and energy as we age. Goulding: “This research suggests that targeted exercise or medications could help preserve muscle energy as we age. While it is still unclear if these mitochondrial changes can be reversed, we are currently exploring how exercise could be used to reduce or prevent some of these age-related changes.”

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