# Eight astronauts had 1,718 blood proteins measured during long missions, and 153 changed as muscle, bone, lipid and brain-related pathways adapted

> Eleven faint signals in astronaut blood may offer a new way to follow how muscles, bones and fat-related chemistry respond to months in microgravity. Researchers found the proteins by using engineered nanoparticles to capture molecules that ordinary blood tests can easily miss....

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Published: 2026-08-22T01:45:03+00:00
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Eleven faint signals in astronaut blood may offer a new way to follow how muscles, bones and fat-related chemistry respond to months in microgravity. Researchers found the proteins by using engineered nanoparticles to capture molecules that ordinary blood tests can easily miss.

The [peer-reviewed study](https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2026.1773221/full), published April 22, 2026, in **Frontiers in Physiology**, examined blood from eight NASA and ESA astronauts who spent at least 180 days in space. Among 1,718 detected proteins, the team identified **11 candidate blood biomarkers** with strong changes after flight.

The findings could help flight doctors follow physical strain during **long-duration spaceflight**, especially as crews prepare for missions farther from Earth. The study abstract states, "Long duration spaceflight leads to significant muscle mass and strength loss, which current inflight countermeasures can only partially mitigate."

## How eight astronauts were tracked

The research followed **eight astronauts**, including five men and three women, with an average age of about 47. Each person provided blood at five points spanning the mission. Samples were collected 60 days before launch, twice during flight and twice after landing.

The first in-flight sample came between mission days 31 and 60. A second was taken about 10 days before the return to Earth. Follow-up samples were collected three to five days after landing and again around 105 days later, giving researchers a view of early flight changes, late flight conditions and recovery.

All participants completed regular exercise during their roughly six-month stays aboard the **International Space Station**. Crews generally exercised for about two and a half hours a day, using endurance equipment along with resistance machines. Muscle loss can continue despite such routines because muscles experience far less weight-bearing force in orbit.

## Nanoparticles uncover scarce blood proteins

Blood carries chemical messages from tissues across the body, yet its most common proteins can hide smaller signals. Albumin, for example, is present at millions or billions of times the concentration of some signaling proteins. Finding a scarce molecule in that mixture resembles hearing a whisper beside a loud engine.

The researchers used the **Proteograph XT** system to search deeper. Its engineered nanoparticles attract different groups of proteins onto their surfaces. Each particle develops a coating called a protein corona, which gathers molecules according to their physical and chemical properties.

After separating and washing the nanoparticles, the team cut the captured proteins into smaller pieces called peptides. A mass spectrometer then measured those pieces. Software compared samples taken before flight with samples collected a few days after landing, revealing changes among **low-abundance proteins** that can be difficult to measure through standard methods.

The analysis detected 1,718 proteins in enough participants to support comparison. A first statistical test found 153 proteins with significant changes. A stricter check, designed to reduce false discoveries, narrowed the group to 11 candidates. The underlying proteomics files were deposited in the [PRIDE data archive](https://www.ebi.ac.uk/pride/archive/) under identifier PXD069732.

## Eleven candidate biomarkers stand out

Several of the strongest changes involved perilipins, proteins associated with fat droplets inside cells. Perilipin-1 increased by 192 percent in early post-flight samples, according to the study table. Myosin regulatory light chain 11 rose by 187 percent, while **perilipin-4** increased by 182 percent.

Other candidates were linked with cartilage and bone-related activity. Osteomodulin and spondin-2 increased after flight, as did collagen alpha-2(XI) chain and collagen triple helix repeat-containing protein 1. Neuroendocrine convertase 1, an enzyme involved in processing hormones and other signaling molecules, also rose.

Two candidates decreased. Haptoglobin-related protein fell by 16 percent, while platelet factor 4 dropped by 37 percent. Platelet factor 4 has roles in blood clotting and inflammatory activity, although the study did not establish what its decline meant for astronaut health.

The team checked three candidates with a second laboratory method across all five collection points. Perilipin-4 rose during flight and remained high soon after landing, then moved toward its earlier level by the final sample. Collagen alpha-2(XI) chain followed a similar upward course, while CTHRC1 rose early in flight and later declined.

## Signals of muscle and bone remodeling

Many of the changing proteins belonged to the **extracellular matrix**, the mesh of collagen and other material that supports cells. Muscles, cartilage, tendons and bones continually repair this framework. Long periods without normal gravity can alter the balance between tissue breakdown and rebuilding.

Computer analysis connected 153 changing proteins with 10 pathways related to muscle function and the cell skeleton. The affected processes included collagen production, actin movement and muscle contraction. Actin forms part of the internal structure that allows muscle cells to produce force.

Several proteins in the blood were also associated with the junctions where nerves communicate with muscles. Changes in myosin light chains, neuropilin-2 and related molecules may reflect the reorganization that occurs when muscles work under reduced load for months.

A separate pathway involved reelin and brain-derived neurotrophic factor, known as BDNF. Both take part in the health and adaptability of nerve cells. The pathway calculation offers a starting point for further research, since blood protein patterns alone cannot measure brain performance or prove that a specific nerve process changed.

## Lipid molecules shift during flight

The scientists also measured **sphingolipids**, a family of fats found in cell membranes. Some sphingolipids act as chemical messengers, helping cells control stress responses, energy use and survival. Their balance can change when tissues face inflammation or metabolic strain.

Total ceramide levels fell in the first in-flight sample, then rebounded in the later flight sample and after landing. Glucosylceramide levels increased. Dihydroceramide and sphingomyelin stayed broadly stable, while dihydrosphingomyelin showed a small rise.

To explore a possible link with muscle, the researchers examined enzymes in muscle samples preserved from an earlier spaceflight study. In samples associated with six-month missions, glucosylceramide synthase increased after flight. Sphingosine kinase 2 decreased, while the enzyme that begins new sphingolipid production remained steady.

The results suggest that existing ceramide may have been redirected toward glucosylceramide production. Changes in this pathway could affect muscle energy use and contraction, although the muscle samples came from previous missions and were available from very few astronauts. The connection therefore remains an early hypothesis.

## HDLBP may reflect a protective response

Another blood signal attracted attention because it remained high for much of the sampling period. **HDL-binding protein**, also called vigilin, increased during both in-flight measurements. Its level stayed elevated after landing and moved partway toward the pre-flight level by the final follow-up.

Despite its name, HDLBP performs jobs that extend beyond its association with high-density lipoprotein. It binds to messenger RNA, the temporary set of instructions cells use to build proteins. Research has also connected it with chromosome stability, protein production in the endoplasmic reticulum and the response to DNA damage.

Spaceflight exposes the body to microgravity and higher radiation levels than people normally receive on Earth. Cells must also adjust to altered fluid movement and shifts in metabolism. The authors propose that increased HDLBP could support protein production and genome repair under these conditions.

The study did not directly test whether HDLBP protected the astronauts' cells. Its rise could reflect several overlapping responses. Future laboratory work will need to measure how changing HDLBP levels affect cell stress and recovery before it can serve as a specific health indicator.

## What the small study can reveal

The repeated sampling design gave each astronaut a personal baseline. Researchers could compare a crew member's later blood with that same person's pre-flight sample, reducing some of the biological differences that complicate studies involving unrelated groups.

The **small sample size** remains an important limit. Human spaceflight studies often include few participants because missions carry only a small number of crew members and medical samples compete with many other experiments for storage and transport. Only 300 microliters of serum from each sample were available for the project.

Two blood draws took place in orbit, leaving long gaps between measurements. Individual exercise records were also unavailable beyond the general mission routines reported elsewhere. Diet, workload, genetics and personal responses to exercise may influence blood chemistry across a six-month mission.

The 11 proteins remain candidate biomarkers. Researchers still need to reproduce the results in additional crews and determine the normal range for each stage of flight. Comparisons with bed rest studies and other Earth-based models could help identify which changes come from reduced muscle loading and which are more closely tied to the wider space environment.

## Blood tests for future deep-space crews

Future missions to the Moon and Mars will place crews far from major medical centers. Communication delays and limited return options will increase the value of compact tests that can track health aboard a spacecraft. ESA has previously explored health devices that can run several checks from a [single drop of blood](https://www.esa.int/Enabling_Support/Space_Engineering_Technology/Astronaut_health_check_with_single_drop_of_blood).

The new biomarkers could eventually contribute to **personalized health monitoring**. A crew member whose muscle-related signals rise quickly might benefit from a revised exercise program. Changes in lipid pathways could guide further checks of metabolism and nutrition, provided future studies confirm what each marker means.

Miniaturized mass spectrometers and biosensors may one day measure selected proteins during flight. Such instruments would need to work with tiny samples, operate reliably for months and produce results that astronauts can interpret with support from medical teams on Earth.

Research into astronaut blood also has possible uses on the ground. Similar molecular changes can appear during long bed rest, aging, or recovery from injury. ESA notes that space health research can inform studies of muscle wasting and weakened bones while supporting crews during [extended stays in space](https://www.esa.int/Science_Exploration/Human_and_Robotic_Exploration/How_space_research_is_advancing_health_on_Earth_and_beyond).

Larger astronaut groups, repeated mission studies and faster onboard measurements will be needed before the candidates become routine medical tools. The current results offer a detailed first map of faint blood signals that may help protect crews during future **deep-space missions**. Broader mission context is available from [NASA's Human Research Program](https://www.nasa.gov/hrp/).