Genetic Expression in Microgravity: What Space Reveals About Our DNA

Genes do not switch on and off at random. They respond to signals in a cell's environment — nutrients, temperature, hormones, mechanical force. Gravity is one of those signals, and it has been present at a constant 9.8 meters per second squared (1G) for every generation of life that has ever evolved on Earth. Take it away, as the International Space Station (ISS) does 400 kilometers up, and thousands of genes shift how active they are, sometimes within hours. NASA's Twins Study, GeneLab's rodent archive, and newer single-cell astronaut data have turned that shift into one of the clearest natural experiments biology has ever run: what happens to a genome when the one environmental force it never expected to lose, disappears.

Why gravity matters to a gene that has never "felt" anything

A gene is a stretch of DNA that gets copied into RNA and, often, translated into protein. Whether that copying happens depends on transcription factors — proteins that dock onto DNA and either recruit or block the machinery that reads it. Transcription factors are activated by upstream signals: a hormone binding a receptor, a stretch in the cell membrane, a drop in oxygen. Mechanical force is one of those upstream signals, and gravity is the most constant mechanical force any cell on Earth ever experiences.

Cells do not have a dedicated "gravity organ" the way an inner ear has vestibular hair cells. Instead, gravity acts on cells indirectly, through the things it constantly does at 1G: it pulls fluid downward, it loads weight-bearing tissue, it keeps cells pressed against surfaces and against each other, and it shapes how nutrients and gases settle and mix in fluid. Remove gravity, and none of those secondary effects happen the same way. Fluid stops settling by density and instead behaves according to surface tension and convection. Cells in a dish or a bioreactor no longer feel the same load on their internal skeleton. Blood and other body fluids that normally pool in the legs redistribute toward the head and chest.

Cells sense all of that through a process biologists call mechanotransduction — literally, "translating mechanical signals." The actin cytoskeleton, a mesh of protein filaments that gives a cell its shape, is under constant tension at 1G. Two proteins called YAP and TAZ sit at the center of this system: when the cytoskeleton is taut, YAP and TAZ get pulled into the nucleus, where they switch on genes tied to growth, stiffness sensing, and cell survival. When cytoskeletal tension drops, as it does when actin filaments relax in microgravity, YAP and TAZ stay in the cytoplasm instead, and that entire gene program goes quiet (Dupont et al., Nature, and follow-up mechanotransduction reviews in Nature Reviews Molecular Cell Biology). It is a bit like a tent: pull the guy-ropes taut and the fabric holds a shape that channels rain a certain way; slacken the ropes and water pools somewhere else entirely. The cell's internal "ropes" are the cytoskeleton, and gravity is one of the main things keeping them taut.

In NASA's Twins Study, roughly 7% of astronaut Scott Kelly's gene expression had still not returned to its pre-flight baseline six months after he landed, following nearly a year aboard the ISS — concentrated in immune function, DNA repair, and mitochondrial genes ([NASA Twins Study, 2019](https://www.nasa.gov/humans-in-space/nasa-twins-study-confirms-preliminary-findings/)).

How researchers actually measure gene expression on the ISS

Sequencing a genome once tells you which genes exist. Measuring gene expression tells you which genes are switched on, and how strongly, at a given moment — and that requires a different pipeline entirely.

Sample collection in orbit. Cell cultures, model organisms such as C. elegans worms and Arabidopsis plants, and tissue from research rodents are grown or maintained aboard the ISS in temperature- and humidity-controlled hardware. Some experiments run for days; others, like plant growth chambers, run for full growth cycles.

Preservation before the fire hits. RNA degrades within minutes once a cell dies, so samples are chemically fixed or flash-frozen at the exact moment researchers want to capture. This is one of the hardest parts of spaceflight biology: a mistimed preservation step ruins months of preparation, and there is no do-over until the next resupply mission.

Return and extraction. Frozen samples come back to Earth aboard SpaceX Dragon or other resupply capsules and are shipped to ground labs, where RNA is extracted from the tissue.

Sequencing and comparison. RNA-sequencing (RNA-seq) reads out which transcripts (RNA copies of genes) are present and in what quantity. Researchers compare flight samples against two separate controls: a "ground control" grown in identical hardware on Earth, and, where possible, samples from the same organism before and after flight. This dual-control design matters because ISS hardware itself — enclosed habitats, altered lighting, CO₂ levels — can shift gene expression independent of gravity, and a well-designed study needs to separate "spaceflight environment" effects from "gravity" effects specifically (GeneLab systems biology study, Nature, 2024).

Deposit into GeneLab. NASA's GeneLab is a public data repository that archives raw and processed omics data from spaceflight experiments, so any lab on Earth can reanalyze it without flying a new mission. This turned spaceflight transcriptomics from a scarce, expensive dataset into something researchers reuse for entirely new questions years after the original experiment ended.

How is gene expression measured differently from DNA sequencing?

DNA sequencing reads the fixed genetic code, which does not change during a mission. Gene expression profiling measures RNA, the working copies of genes that are actively being read at a given moment, so it captures which genes are turned up or down in response to conditions like microgravity, rather than what genes exist in the first place.

The Twins Study: one genome, two environments, one clean comparison

The most direct human evidence comes from NASA's Twins Study, which ran from March 2015 to March 2016. Astronaut Scott Kelly spent 340 days aboard the ISS while his identical twin brother, retired astronaut Mark Kelly, stayed on Earth. Because the twins share nearly identical DNA, researchers could isolate the effect of the spaceflight environment on gene expression without needing to control for genetic variation between two unrelated people.

The results, published across several NASA-affiliated papers, showed that immune-related genes changed activity noticeably in flight, that Scott Kelly's genomic instability (a measure of DNA damage and chromosomal irregularity) increased, and that his telomeres — the protective caps on the ends of chromosomes — unexpectedly lengthened during flight rather than shortening as researchers had predicted (NASA Twins Study, 2019; GenomeWeb summary). Within 48 hours of landing, however, Kelly's telomeres shortened sharply, overshooting past his pre-flight baseline before gradually settling. Most gene expression changes reverted to baseline within about six months. But roughly 7% of the genes affected did not fully return, clustering in immune function, DNA repair, bone formation, hypoxia response, and mitochondrial activity (NIA summary of NASA Twins Study).

That mismatch between "temporary" and "persistent" changes is the single most important finding in the whole field. It tells researchers that microgravity is not simply a uniform stressor that fades the moment gravity returns — some gene networks reset quickly, and others carry a kind of molecular scar.

What newer crew data adds: immune suppression at the single-cell level

The Twins Study looked at bulk tissue — a mixture of many cell types averaged together. Newer missions have gone further. The Inspiration4 mission, the first all-civilian orbital spaceflight, gave researchers single-cell, multi-omic data from its four crew members, tracking gene expression cell type by cell type rather than as an average (Inspiration4 crew multi-ome study, Nature Communications, 2024).

That study found T cells — the immune cells responsible for recognizing and killing infected or cancerous cells — showed increased activity of FOXP3, a gene associated with regulatory T cells that dial the immune response down rather than up. Genes for MHC class I, the molecular tags cells use to display their internal contents to the immune system so it can spot infection, showed long-term suppression. A separate ISS crew transcriptome study reported the same broad pattern: functional enrichment at the transition into spaceflight pointed toward immune suppression and reduced cell proliferation, while the transition back to Earth showed a reactivation of immune gene programs (leukocyte transcriptome study, PMC).

A separate transcriptomics analysis of astronaut blood cells found signs of mitochondrial dysfunction alongside markers of T cell exhaustion, a state in which T cells lose some of their ability to respond effectively to threats even though they remain present in the blood (mitochondrial dysfunction and T cell exhaustion study, PMC). Put together, these findings offer a mechanistic explanation for something flight surgeons have observed clinically for decades: astronauts are more prone to reactivation of latent viruses, such as herpesviruses, during and shortly after long missions. The gene expression data shows the immune system is not simply "busy" in space — specific transcriptional programs that keep infection surveillance running are being dialed down.

What rodent and plant missions show that human studies cannot

Human astronaut missions are expensive, rare, and ethically limited in what tissue researchers can sample. Rodent missions and plant experiments fill that gap, because researchers can examine organs — brain, muscle, bone, mammary tissue — that no one would biopsy from a living astronaut.

NASA's GeneLab archive aggregates this rodent transcriptomic data across dozens of missions, and a 2024 systems-biology reanalysis of seven separate rodent spaceflight datasets identified a small set of "master regulator" genes that seem to coordinate the broader response to microgravity and space radiation together, with the signaling molecule TGF-β1 emerging as the most consistently implicated regulator across studies (GeneLab master regulator analysis, PMC). TGF-β1 is already well studied on Earth for its role in wound healing, immune regulation, and tissue remodeling, which gives researchers an existing pharmacological toolkit to test hypotheses about spaceflight biology without starting from zero.

Circadian clock genes — the internal genetic timekeepers that normally stay synchronized across organs via light and activity cues — also show disruption in spaceflight mice. A reanalysis of archived GeneLab RNA-seq data found that clock gene expression became desynchronized between different peripheral tissues in flight mice compared to ground controls, suggesting that the loss of normal light-dark and activity cycles aboard the ISS ripples down into cellular-level timing systems, not just sleep behavior (clock gene asynchrony study, Life, 2020).

Plants respond just as clearly, though through a different sensing mechanism. Arabidopsis thaliana, a small flowering plant used widely in genetics because of its fully sequenced genome, shows large-scale transcriptional network changes in microgravity, particularly in genes tied to gravitropism — the process by which roots normally grow down and shoots grow up in response to gravity (Arabidopsis spaceflight network analysis, PMC). Plants sense gravity using starch-filled organelles called statoliths that settle to the low side of specialized cells; without gravity, those organelles stop settling directionally, and the genetic program that would normally direct growth accordingly loses its input signal entirely.

Not every change traces back to gravity alone. A GeneLab systems-biology study comparing rodents housed in flight-matched enclosure modules found that elevated CO₂ levels inside ISS habitats were themselves an independent transcriptomic stressor, associated with reduced metabolic gene activity, altered immune signaling, and activation of pathways linked to tumor growth — separate from microgravity itself (CO₂ as an environmental stressor, GeneLab study, PMC). That finding is a genuine methodological headache for the field: any spaceflight experiment has to disentangle gravity's effect from the effects of confinement, radiation, altered CO₂, and disrupted light cycles, all of which happen simultaneously.

The single most surprising finding across two decades of spaceflight transcriptomics is not that genes change in space — it is that a meaningful fraction of those changes in Scott Kelly's genome had not fully reset six months after he was back on Earth, breathing 1G air, eating 1G food, sleeping in a 1G bed.

What this table of major gene-expression categories actually shows

The table below summarizes the major functional categories of genes repeatedly identified across ISS and GeneLab transcriptomic studies, and what each shift is thought to reflect biologically.

Gene category	Typical direction in microgravity	What it suggests
Immune function (T cell, MHC class I)	Suppressed	Reduced pathogen surveillance, latent virus reactivation risk
Mechanotransduction (YAP/TAZ targets, cytoskeletal genes)	Suppressed	Cells losing normal mechanical load cues
DNA repair	Altered, mixed direction	Interaction with cosmic radiation exposure, not gravity alone
Mitochondrial activity	Altered, often reduced efficiency	Possible link to fatigue and metabolic changes
Circadian clock genes	Desynchronized across tissues	Loss of normal light/activity entrainment
Bone formation genes	Suppressed	Consistent with measurable bone density loss in long missions
Gravitropism genes (plants)	Signal input lost	Statolith-based gravity sensing has no directional cue

Table: major gene categories with reproducible expression shifts in spaceflight transcriptomic studies, compiled from NASA Twins Study, GeneLab, and peer-reviewed spaceflight transcriptomics papers cited throughout this article.

Why this matters beyond astronauts

It would be easy to file all of this under "interesting but only relevant to the handful of people who fly to space." That undersells it. Spaceflight is an extreme, fast-acting version of processes that also happen more slowly on Earth, which makes it a useful accelerant for studying diseases that normally take years to develop.

Immune aging. The suppressed T cell activity and MHC class I downregulation seen in astronauts resembles, in some respects, immunosenescence — the gradual decline in immune function that happens with normal human aging. Researchers studying astronaut immune data are explicitly drawing on it as a compressed timeline for age-related immune decline, since changes that might take a decade to accumulate on Earth show up within weeks in orbit.

Bone and muscle loss mechanisms. Suppressed bone-formation gene activity in microgravity parallels processes seen in osteoporosis and in prolonged bed rest on Earth, giving researchers a genetic entry point into a condition that is otherwise difficult to study in real time. For a detailed look at how this plays out at the tissue and rehabilitation level, see our companion piece on muscle atrophy in space.

Cancer biology in a different mechanical environment. Removing the mechanical loading that YAP/TAZ signaling depends on changes how some cells grow and organize, which is part of why cancer researchers have taken an interest in microgravity as an unconventional model system. Our related article on cancer cell behavior in zero-G goes deeper into what tumor cells specifically do differently off-Earth.

Drug and protein research enabled by the same missions. Many of the same ISS facilities used for gene expression studies also host protein crystallization experiments, because the absence of gravity-driven convection lets some protein crystals grow larger and more ordered than they can on Earth — a separate but related benefit of the microgravity environment, covered in our piece on protein crystal growth in microgravity.

A gene-editing connection. Some of the genes flagged as gravity-responsive, including DNA repair genes, are also targets researchers study using CRISPR-based tools to understand or correct genetic disease on Earth. If you want the mechanics of how that editing technology actually works, see our explainer on CRISPR gene editing.

What people get wrong about "space changes your DNA"

Confusion 1: Gene expression change is not DNA mutation. Headlines occasionally compress "Scott Kelly's gene expression changed" into "Scott Kelly's DNA changed," which is not accurate. His underlying DNA sequence stayed the same; what changed was how actively different genes were being transcribed into RNA. That distinction matters enormously: a mutation is a permanent change to the genetic code itself, while an expression change is more like a dimmer switch being turned up or down on genes that were already there.

Confusion 2: "Reversible" does not mean "instant" or "complete." Most gene expression changes measured in astronauts did trend back toward pre-flight baselines, but on a timescale of months, not the moment their boots touched the runway. And as the Twins Study showed, a meaningful subset of genes never fully returned within the study's observation window.

Confusion 3: Microgravity is not the only variable at play. It is tempting to attribute every spaceflight gene expression change to gravity loss alone. In reality, cosmic radiation exposure, elevated cabin CO₂, disrupted circadian lighting, psychological stress, and altered diet all happen simultaneously aboard the ISS, and well-designed studies go to considerable lengths to separate these variables rather than assume gravity is the sole cause of every observed shift.

Confusion 4: Model organism findings do not automatically transfer to humans. A gene network identified as a "master regulator" in mice, such as TGF-β1 signaling, is a strong lead for human research, not a confirmed human mechanism. Cross-species validation is an ongoing, incomplete part of the field, and researchers are careful to flag rodent findings as hypothesis-generating rather than clinically established in people.

What this means

Gravity is not a passive backdrop that biology simply happens inside of — it is an active input that cells read continuously through mechanical sensing systems like the YAP/TAZ pathway, and removing it triggers a coordinated, measurable shift across thousands of genes. The NASA Twins Study and the growing GeneLab archive turned that shift from a curiosity into a genuine research tool: a fast, extreme model for immune aging, bone loss, and cellular stress that would otherwise take years to observe on Earth. The open question the field is still working through is which of those changes are unique to spaceflight, and which are simply an accelerated version of processes already happening in all of us, just too slowly on the ground to notice.

FAQ

Q: How many genes are affected by microgravity? A: Studies vary by organism and tissue, but NASA's Twins Study found roughly 7% of astronaut Scott Kelly's gene expression had not returned to baseline six months after landing, and GeneLab rodent datasets consistently identify thousands of differentially expressed genes across immune, metabolic, and structural gene categories.

Q: Does spaceflight change your actual DNA sequence? A: No, not in the way gene expression changes do. Gene expression measures how actively existing genes are being read into RNA, not whether the underlying DNA code itself has mutated. Separate research tracks DNA damage and chromosomal instability, which are different phenomena from expression changes.

Q: What is the NASA Twins Study and why was it useful? A: It compared astronaut Scott Kelly, who spent 340 days on the ISS, against his identical twin brother Mark Kelly, who stayed on Earth. Because the twins share nearly identical genomes, researchers could isolate the spaceflight environment's effect on gene expression without genetic variation confounding the comparison.

Q: Are gene expression changes in space reversible? A: Most changes trend back toward pre-flight levels within about six months, but not instantly, and not completely. A subset of genes tied to immune function, DNA repair, and mitochondrial activity remained altered in Scott Kelly's data even after six months back on Earth.

Q: How do cells sense the absence of gravity? A: Primarily through mechanotransduction, the process by which cells convert mechanical forces into chemical and genetic signals. Proteins including YAP and TAZ respond to tension in the cell's cytoskeleton, moving into the nucleus to activate genes when tension is high and staying out when it drops, as it does in microgravity.

Q: Why does spaceflight suppress the immune system? A: Multiple studies show suppressed T cell activity and reduced MHC class I gene expression, the genes responsible for displaying a cell's internal contents to the immune system. Researchers link this to increased latent virus reactivation observed in astronauts, though the exact combination of causes, including radiation and stress, is still being worked out.

Q: Do plants respond to microgravity the same way animal cells do? A: Not through the same mechanism. Plants sense gravity using starch-filled organelles called statoliths that normally settle downward inside specialized cells; without gravity, that directional settling stops, disrupting the genetic programs that guide root and shoot growth.

Q: Is CO2 level in the ISS a confounding factor in these studies? A: Yes. A GeneLab systems-biology study found that elevated cabin CO2 levels were independently associated with transcriptomic changes, including altered metabolism and immune signaling, separate from microgravity itself, which is why researchers use tightly matched ground controls.

Q: Can findings from mouse spaceflight studies be applied directly to humans? A: Not automatically. Mouse studies, including GeneLab's identification of TGF-β1 as a possible master regulator of the spaceflight response, generate strong hypotheses for human research but require independent validation in human tissue before being treated as confirmed mechanisms.

Q: What real-world research benefits from studying gene expression in space? A: Researchers use spaceflight-induced immune suppression as an accelerated model for age-related immune decline, use suppressed bone-formation genes to study osteoporosis mechanisms, and use altered mechanotransduction signaling to study how tumor cells behave outside their normal mechanical environment.

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Read next:

• CRISPR Gene Editing: The Invention That Rewrites DNA
• Biological Aging in Microgravity: What the ISS Reveals About Aging Processes
• Protein Crystal Growth in Microgravity: Solving Disease at 400km Altitude
• Cancer Cell Behavior in Zero-G: How Microgravity Changes Tumor Growth
• Muscle Atrophy Research: How Weightlessness Weakens Astronauts

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Sources:

• NASA Twins Study Confirms Preliminary Findings, NASA.gov (2019)
• NASA Twins Study Reveals Health Effects of Space Flight, National Institute on Aging
• NASA Twins Study Finds Space-Linked Changes to Gene Expression, Telomere Length, GenomeWeb
• Single-cell multi-ome and immune profiles of the Inspiration4 crew, Nature Communications (2024)
• The transcriptome response of astronaut leukocytes to long ISS missions, PMC
• Transcriptomics analysis of mitochondrial dysfunction and T cell exhaustion in astronauts, PMC
• NASA GeneLab derived microarray studies across altered gravitational conditions, npj Microgravity / Nature (2024)
• A microRNA signature and TGF-β1 response as master regulators for spaceflight response, PMC / PLOS ONE
• Integrated RNA-seq analysis indicates asynchrony in clock genes between tissues under spaceflight, PMC / Life (2020)
• Network analysis of gene transcriptions of Arabidopsis thaliana in spaceflight microgravity, PMC
• Global transcriptomic analysis suggests carbon dioxide as an environmental stressor in spaceflight, PMC
• Role of YAP/TAZ in mechanotransduction, Nature
• Mechanobiology of YAP and TAZ in physiology and disease, Nature Reviews Molecular Cell Biology