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Skin & Muscle

Spacelike Microgravity Accelerates Aging and Causes Muscle Loss

Human muscle cells grown in reduced gravity to mimic spaceflight show signs of aging, including diminished growth and regeneration.

Vadim Sadovski | Shutterstock
By Daniel R. Miranda, Ph.D.

Highlights: 

  • Resistance exercise alone isn’t enough to prevent age-related or microgravity-induced muscle loss. 
  • Aging and microgravity-related muscle loss stem from diminished muscle growth potential. 
  • Age-related and microgravity-induced muscle loss may share effective treatment options. 

In space, although astronauts appear weightless, they still depend on their muscles to live. Whether in space or down here on Earth, we need our muscles to execute an array of vital functions from conscious movement to unconscious heartbeats and breathing. If we ever want to get to Mars or reach the outer edges of the solar system, we’re going to need healthy muscles. There’s just one problem: space travel appears to speed up the loss of muscle function and regenerative abilities.

As reported in Biochemical and Biophysical Research Communications, Takahashi and colleagues from Tokyo Women’s University in Japan showed that human muscle cells subjected to simulated microgravity show signs of aging, including diminished muscle regeneration. Their study explains why astronauts have trouble preventing muscle loss even with exercise. Utilizing this model of microgravity in a dish can help us better prepare to shoot for the stars by understanding the effects of space travel here on Earth.

Exercise Isn’t Enough for Muscle Regeneration in Space

As we venture away from the Earth’s surface and into space, there’s a good chance that the amount of gravity will decrease as long as we don’t come within the gravitational pull of a stellar or planetary object. That’s why gravity on the International Space Station (ISS), which orbits the earth, is about 90% of what it is here on the planet’s surface. The phenomenon of reduced gravity is called microgravity.

With this decrease in gravity, maintaining muscle mass becomes difficult. Astronauts can offset this somewhat with resistance exercise in space. However, even when exercising for several hours a day, astronauts still lose muscle. Interestingly, the elderly have the same problem; training is not enough to completely prevent muscle loss. Coincidence? Takahashi and colleagues show that it is not.

Bringing Microgravity Down to Earth 

Much of our current understanding of microgravity’s effect on the living body comes from animal studies done on the ISS. However, due to the limitations of conducting these studies, researchers on earth have begun using gravity-control devices, which utilize rotational movements to simulate microgravity. So far, many of these studies have only been done on animals. Takahashi and colleagues are among the first to use a gravity-control device on human muscle cells. 

Muscle regeneration involves generating new muscle cells in response to damage like damage caused by resistance exercise. Muscle regeneration prevents muscle loss by promoting muscle growth. In aged muscle, muscle regeneration is diminished, helping to explain why resistance exercise does not entirely prevent muscle loss in the elderly. The question is whether reduced muscle regeneration also explains why exercise is not enough for astronauts.

Microgravity Ages Muscle Cells

To study the effects of microgravity on muscle cells, Takahashi and colleagues compared human muscle cells grown under simulated microgravity to human muscle cells grown under normal gravity. They found that the muscle cells grown in microgravity reproduced (proliferated) about half as much as the normal cells. As muscle cell reproduction is a critical aspect of muscle regeneration, this lack of reproduction would suggest that microgravity inhibits muscle regeneration.  

(Takahashi et al., 2021 | Biochem Biophys Res Commun.) Lack of muscle cell reproduction in microgravity. (a) Muscle cells were grown in a dish (cell culture) and placed in a microgravity simulator. (b) Muscle cells subjected to microgravity (µM) reproduced less than cells in normal gravity (1G) after 3 and 6 days. (c) Quantification of cells each day in the simulator; the number of cells grown in µG each day was less than cells grown in 1G. 

After removing the muscle cells from microgravity, simulating an astronaut coming home to Earth, Takahashi and colleagues found that the microgravity-affected muscle cells looked more like “old” muscle cells. Both the “old” cells, which regrew multiple times to mimic aging, and the microgravity-affected cells were bigger and had larger nuclei than the “young” cells, which were only grown once. The “old” and microgravity-affected cells also showed signs of permanent inactivation (senescence), which stops cells from reproducing and is what occurs typically in aged human cells. 

When astronauts come back to Earth from space flight, they eventually recover their muscle mass. As described above, even after removing the muscle cells from microgravity, the signs of aging were not reversed. The authors point out that this is likely because new cells were not provided to the microgravity-affected cells. This is not what would happen in the human body, which would generate new cells. Therefore, astronauts likely recover upon returning to earth because muscle regeneration is restored. 

(Takahashi et al., 2021 | Biochem Biophys Res Commun.) Microgravity and aging diminish muscle cell size. Muscle cells were removed from microgravity and studied. (a-d) µG cells appear bigger and flatter than 1G cells (e) Graph showing area (size) of cells; µG cells are the same size as old cells, and both are larger than young cells.

Microgravity Reduces Muscle Regeneration

Muscle regeneration and development are very similar processes. In both cases, new muscle cells are generated and fuse to form mature muscle cells. Takahashi and colleagues looked at two proteins associated with normal muscle development and regeneration called Myf5 and desmin. The Japanese scientists found that both proteins were reduced in microgravity-affected muscle cells. In the “old” cells, Myf5 was essentially absent.

In addition, many of the microgravity-affected cells were unable to develop into mature muscle cells and, when they did, they were smaller than usual. Development into mature muscle cells is the final step in muscle regeneration and development. So, these findings indicate that microgravity-affected muscle cells regenerate less. 

Shared Prospects for Treating Muscle Loss

Similar experiments on human muscle cells will have to be conducted on the ISS or another orbiting spacecraft with real-life microgravity. The authors state, “We must be mindful of the differences that exist between ground-based experiments and weightless conditions in space. The difference between real and simulated microgravity needs to be considered in future works.”

In addition, whole animal and human studies are needed to confirm that microgravity reduces muscle regeneration and accelerates aging. Importantly, these studies will help us better understand muscle regeneration itself. There are still important questions that need answers: how can we prevent or reverse the decline of muscle regeneration? So far, it seems that we can answer this, and there are prospects for a shared treatment for both age-related and microgravity-induced muscle loss. 

Source

Takahashi H, Nakamura A, Shimizu T. Simulated microgravity accelerates aging of human skeletal muscle myoblasts at the single cell level. Biochem Biophys Res Commun. 2021 Nov 12;578:115-121. doi: 10.1016/j.bbrc.2021.09.037.

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