Space exploration

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Human muscle cells come back from space, look aged

Biology, gene activity, muscle cells, Science, Space, Space exploration / /

Putting some muscle into it —

Astronauts’ muscles atrophy in space, but we can identify the genes involved.

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Image of two astronauts in an equipment filled chamber, standing near the suits they wear for extravehicular activities.

Enlarge / Muscle atrophy is a known hazard of spending time on the International Space Station.

Muscle-on-chip systems are three-dimensional human muscle cell bundles cultured on collagen scaffolds. A Stanford University research team sent some of these systems to the International Space Station to study the muscle atrophy commonly observed in astronauts.

It turns out that space triggers processes in human muscles that eerily resemble something we know very well: getting old. “We learned that microgravity mimics some of the qualities of accelerated aging,” said Ngan F. Huang, an associate professor at Stanford who led the study.

Space-borne bioconstructs

“This work originates from our lab’s expertise in regenerative medicine and tissue engineering. We received funding to do a tissue engineering experiment on the ISS, which really helped us embark on this journey, and became curious how microgravity affects human health,” said Huang. So her team got busy designing the research equipment needed to work onboard the space station. The first step was building the muscle-on-chip systems.

“A lot of what was known about how space affects muscles was gathered through studying the astronauts or studying animals like mice put in microgravity for research purposes,” Huang said. “In some cases, there were also in vitro cultured cells on a Petri dish—something very basic. We wanted to have something more structurally complex.” Her team developed a muscle-on-chip platform in which human myotubes, cells that organize into long parallel bundles that eventually become muscle fibers in a living organism, were grown on collagen scaffolds. The goal was to make the samples emulate real muscles better. But that came with a challenge: keeping them alive on the ISS.

“When we grow cells on Earth, we pour the medium—basically a liquid with nutrients that allow the cells to grow—over the cells, and everything is fine,” Huang said. “But in space, in the absence of gravity, we needed a closed, leak-proof, tightly sealed chamber. The medium was sloshed around in there.”

Oxygen and carbon dioxide levels were maintained with permeable membranes. Changing the medium was a complicated procedure involving syringes and small custom-designed ports. But getting all this gadgetry up and running was worth it in the end.

Genes of atrophy

Huang’s team had two sets of muscle-on-chip systems: one on the ground and one on the ISS. The idea of the study was to compare the genes that were upregulated or downregulated in each sample set. It turned out that many genes associated with aging saw their activity increase in microgravity conditions.

This result was confirmed when the team analyzed the medium that was taken off after the cells had grown in it. “The goal was to identify proteins released by the cells that were associated with microgravity. Among those, the most notable was the GDF15, which is relevant to different diseases, particularly mitochondrial dysfunction or senescence,” said Huang.

Overall, the condition of cells on the ISS was somewhat similar to sarcopenia, an age-related muscle loss disease. “There were some similarities, but also a lot of differences. The reason we didn’t make sarcopenia the main focus of this study is that we know our muscle-on-chip system is a model. It’s mostly muscle cells on a scaffold. It doesn’t have blood vessels or nerves. Comparing that to clinical, real muscle samples is a bit tricky, as it is not comparing apples to apples,” said Huang.

Nevertheless, her team went on to use their ISS muscle-on-chip samples to conduct proof-of-concept drug screening tests. Drugs they tested included those used to treat sarcopenia, among other conditions.

Space drugs

“One of the drugs we tested was the [protein] IGF 1, which is a growth factor naturally found in the body in different tissues, especially in muscles. When there is an injury, IGF 1 activates within a body to initiate muscle regeneration. Also, IGF 1 tend to be declined in aging muscles,” said Huang. The second drug tested was 15-PGDH-i, a relatively new inhibitor of enzymes that hinder the process of muscle regeneration. Used on the muscles-on-chip on the ISS, the drugs partially reduced some of the microgravity-related effects.

“One of the limitations of this work was that on the ISS, the microgravity is also accompanied by other factors, such as ionizing radiation, and it is hard to dissociate one from the other,” said Huang. It’s still unclear if the effects observed in the ISS samples were there due to radiation, the lack of gravity, both, or some additional factor. Huang’s team plans to do similar experiments on Earth in simulated microgravity conditions. “With some of the specialized equipment we recently acquired, it is possible to look at just the effects of microgravity,” Huang said. Those experiments are aimed at testing a wider range of drugs.

“The reason we do this drug screening is to develop drugs that could either be taken preemptively or during the flight to counteract muscle atrophy. It would probably be more feasible, lighter, and cheaper than doing artificial gravity concepts,” Huang said. The most promising candidate drugs selected in these ground experiments will be tested on Huang’s muscle-on-chip systems onboard the ISS in 2025.

Stem Cell Reports, 2024. DOI: 10.1016/j.stemcr.2024.06.010

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Astronauts find their tastes dulled, and a VR ISS hints at why

food, Human behavior, international space station, Science, Space exploration, taste / /

Pass the sriracha —

The visual environment of the ISS seems to influence people’s experience of food.

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Image of astronauts aboard the ISS showing off pizzas they've made.

Enlarge / The environment you’re eating in can influence what you taste, and space is no exception.

Astronauts on the ISS tend to favor spicy foods and top other foods with things like tabasco or shrimp cocktail sauce with horseradish. “Based on anecdotal reports, they have expressed that food in space tastes less flavorful. This is the way to compensate for this,” said Grace Loke, a food scientist at the RMIT University in Melbourne, Australia.

Loke’s team did a study to take a closer look at those anecdotal reports and test if our perception of flavor really changes in an ISS-like environment. It likely does, but only some flavors are affected.

Tasting with all senses

“There are many environmental factors that could contribute to how we perceive taste, from the size of the area to the color and intensity of the lighting, the volume and type of sounds present, the way our surroundings smell, down to even the size and shape of our cutlery. Many other studies covered each of these factors in some way or another,” said Loke.

That’s why her team started to unravel the bland ISS food mystery by recreating the ISS environment in VR. “Certain environments are difficult to be duplicated, such as the ISS, which led us to look at digital solutions to mimic how it felt [to be] living and working in these areas,” said Julia Low, a nutrition and food technologist at the RMIT University and co-author of the study.

Once the VR version of the ISS was ready, the team had 54 participants smell flavors of vanilla, almonds, and lemon. The first round of tests was done in a pretty normal room, and the second with the VR goggles on, running the simulated ISS environment complete with sterile, cluttered spaces, sounds present at the real ISS, and objects floating around in microgravity.

The participants said the lemon flavor seemed the same in both rounds. Almonds and vanilla, on the other hand, seemed more intense when participants were in the VR environment. While that’s the opposite of what might be expected from astronauts’ dining habits, it is informative. “The bottom line is we may smell aromas differently in a space-like environment, but it is selective as to what kind of aromas. We’re not entirely sure why this happens, but knowing that a difference exists is the first step to find out more,” Loke said.

Loke and her colleagues then pulled out a mass spectrometer and took a closer look at the composition of the flavors they used in the tests.

Space-ready ingredients

The lemon flavor in Loke’s team tests was lemon essential oil applied to a cotton ball, which was then placed in a closed container that was kept sealed until it was given to the participants to smell. The vapors released from the container contained several volatile chemicals such as limonene, camphene, 3-carene, and monoterpene alcohols like linalool, carveol, and others.

Almond flavors contained similar chemicals, but there was one notable difference: the almond and vanilla flavors contained benzaldehyde, while the lemon did not. “Benzaldehyde naturally gives off a sweet aroma, while the lemon aroma, which did not have it, has a more fruity and citrusy aroma profile. We believe that it may be the sweet characteristics of aromas that leads to a more intense perception in [simulated] space,” said Loke.

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Building robots for “Zero Mass” space exploration

materials science, robotics, Science, Space, Space exploration / /
A robot performing construction on the surface of the moon against the black backdrop of space.

Sending 1 kilogram to Mars will set you back roughly $2.4 million, judging by the cost of the Perseverance mission. If you want to pack up supplies and gear for every conceivable contingency, you’re going to need a lot of those kilograms.

But what if you skipped almost all that weight and only took a do-it-all Swiss Army knife instead? That’s exactly what scientists at NASA Ames Research Center and Stanford University are testing with robots, algorithms, and highly advanced building materials.

Zero mass exploration

“The concept of zero mass exploration is rooted in self-replicating machines, an engineering concept John von Neumann conceived in the 1940s”, says Kenneth C. Cheung, a NASA Ames researcher. He was involved in the new study published recently in Science Robotics covering self-reprogrammable metamaterials—materials that do not exist in nature and have the ability to change their configuration on their own. “It’s the idea that an engineering system can not only replicate, but sustain itself in the environment,” he adds.

Based on this concept, Robert A. Freitas Jr. in the 1980s proposed a self-replicating interstellar spacecraft called the Von Neumann probe that would visit a nearby star system, find resources to build a copy of itself, and send this copy to another star system. Rinse and repeat.

“The technology of reprogrammable metamaterials [has] advanced to the point where we can start thinking about things like that. It can’t make everything we need yet, but it can make a really big chunk of what we need,” says Christine E. Gregg, a NASA Ames researcher and the lead author of the study.

Building blocks for space

One of the key problems with Von Neumann probes was that taking elements found in the soil on alien worlds and processing them into actual engineering components was resource-intensive and required huge amounts of energy. The NASA Ames team solved that with using prefabricated “voxels”—standardized reconfigurable building blocks.

The system derives its operating principles from the way nature works on a very fundamental level. “Think how biology, one of the most scalable systems we have ever seen, builds stuff,” says Gregg. “It does that with building blocks. There are on the order of 20 amino acids which your body uses to make proteins to make 200 different types of cells and then combines trillions of those cells to make organs as complex as my hair and my eyes. We are using the same strategy,” she adds.

To demo this technology, they built a set of 256 of those blocks—extremely strong 3D structures made with a carbon-fiber-reinforced polymer called StattechNN-40CF. Each block had fastening interfaces on every side that could be used to reversibly attach them to other blocks and form a strong truss structure.

A 3×3 truss structure made with these voxels had an average failure load of 900 Newtons, which means it could hold over 90 kilograms despite being incredibly light itself (its density is just 0.0103 grams per cubic centimeter). “We took these voxels out in backpacks and built a boat, a shelter, a bridge you could walk on. The backpacks weighed around 18 kilograms. Without technology like that, you wouldn’t even think about fitting a boat and a bridge in a backpack,” says Cheung. “But the big thing about this study is that we implemented this reconfigurable system autonomously with robots,” he adds.

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