Why Astronauts’ Bodies Waste Away in Space: New ISS Study Pinpoints Failing Mitochondria as the Root Cause
Featured image: JAXA astronaut Soichi Noguchi working with cell culture experiments in the Kibo module on the ISS; credit: JAXA/NASA
Astronauts lose muscle mass and bone density in space, a well-known problem that has limited long-duration spaceflight for decades. Now a study published July 16 in Nature Communications (DOI: 10.1038/s41467-026-10783-2) has traced the root cause to a specific molecular mechanism: microgravity disrupts the ability of mitochondria to produce their own proteins, creating an energy deficit that drives tissue wasting throughout the body.
The findings, based on experiments conducted aboard the International Space Station’s Kibo module by JAXA astronaut Soichi Noguchi, identify a complete mechanosensory pathway that links the force of gravity to cellular energy production. The work provides a molecular target for countermeasures that could protect astronauts on a three-year Mars mission.
What the Study Found
The research team, led by Wakigawa and colleagues, used a technique called ribosome profiling on human cells and C. elegans worms cultured aboard the ISS to measure protein production genome-wide. They found that after just 24 hours in microgravity, the 13 proteins encoded by mitochondrial DNA had significantly fewer ribosomes attached to them, meaning their production was suppressed.
The effect was highly specific. Nuclear-encoded proteins destined for the mitochondria showed no change. Only the mitochondria’s own genome was affected. And crucially, the same effect appeared in human cells, worms, and mice, indicating a fundamental biological mechanism conserved across all eukaryotes.
After 48 hours in microgravity, the cells showed partial adaptation, but mitochondrial translation remained depressed.
The Molecular Pathway
The paper describes a complete signaling chain from gravity to mitochondrial function:
1. Cells sense gravity through how strongly they adhere to the surrounding matrix, via laminin-integrin cell adhesion proteins
2. This mechanical signal travels through a cascade: integrin to FAK to RAC1 to PAK1 to BAD to Bcl-2 family proteins
3. The signal reaches the mitochondrial fatty acid synthesis (mtFAS) pathway, which consumes a molecule called malonyl-CoA
4. When gravity weakens, malonyl-CoA accumulates and causes lysine malonylation of the mitochondrial translation machinery, suppressing both the initiation and elongation phases of protein production.
The result is fewer mitochondrial proteins, less ATP generation, and ultimately less energy for muscle contraction and repair.
Hypergravity (10 times Earth gravity) did the opposite, activating mitochondrial translation. And the effect was reversible: returning cells to normal gravity restored production.
Connecting to the Known Problem
Scientists have known for years that astronauts’ muscles waste away in space. Biopsies from astronauts after six months on the ISS showed dramatic downregulation of the mitochondrial proteome, particularly in the soleus muscle, a postural anti-gravity muscle that is the first and most severely affected.
The new study provides a unified molecular explanation for these observations. The soleus muscle is exactly the tissue where mechanical load is most reduced in microgravity, and the mouse model in the study confirmed that hindlimb unloading reduced mitochondrial translation through the same pathway.
“This mechanism is separate from radiation damage or oxidative stress,” the authors noted. The team explicitly ruled out mitochondrial DNA damage, fragmentation, or stress responses, confirming that this is a pure mechanosensory effect.
Why It Matters for Mars
A round-trip Mars mission lasting approximately three years would expose astronauts to continuous microgravity, making muscle and bone wasting a critical biomedical barrier. The identification of mitochondrial dysfunction as an upstream cause, rather than a downstream consequence, opens new avenues for countermeasures.
The most straightforward intervention is mechanical: exercise and artificial gravity would directly activate the FAK-to-mtFAS signaling cascade. Astronauts who exercise more already show better preservation of muscle mass and mitochondrial function. But exercise alone may be insufficient for multi-year missions.
The paper identifies several potential pharmacological targets:
- Laminin-integrin agonists to artificially strengthen cell adhesion signaling
- FAK activators to bypass the gravity-sensing step
- mtFAS pathway boosters that prevent malonylation of the translation machinery
- Sirt5 activators to reverse the suppressive chemical modification
“These findings provide a roadmap for developing drugs that could preserve muscle and bone health during deep space missions,” the authors concluded.