Space travel goes boldly into human immune aging research

Scientists show how space travel disrupts immune function, offering new strategies to maintain immunity in space and combat aging on Earth.

Since humans first started traveling across the final frontier, astronauts have consistently encountered significant health challenges arising from the extreme conditions of space flight – particularly the reduction in gravitational force.

Now in a pioneering study, researchers led by scientists at The Buck Institute have revealed, for the first time, the effects of microgravity on immune system cells with single-cell resolution. Published in Nature Communications, their comprehensive paper examines the impact of gravity on immune cells and identifies “space nutraceuticals” designed to counteract the deleterious effects of microgravity on these cells.

Longevity.Technology: The health of astronauts during space missions, particularly as we plan for return trips to the Moon, voyages to Mars and beyond, is of paramount importance. Space travel is hazardous, exposing space travellers to microgravity and other extreme conditions that can profoundly impact the immune system and lead to heightened risks of infections and other health issues. However, these challenges present unique opportunities for geroscience advancement; research into the effects of space travel on human physiology, such as the recent findings in this paper, not only aids in developing interventions to keep astronauts healthy but also accelerates our understanding of aging and longevity on Earth. By simulating space-like conditions and observing their impacts on the immune system, we can uncover valuable insights into the mechanisms of immune aging and devise strategies to mitigate its effects, benefiting both space travelers and those with their feet on terra firma alike.

“We show how simulated microgravity shapes immune cells and how the changes in force alter the cells’ function at the single cell level,” said Associate Professor Daniel Winer, MD, co-senior author on the new paper. “This level of resolution is new and exciting in understanding the effects of microgravity on cells.”

Using cells in simulated microgravity, combined with data from space flight from astronauts and mice aboard the International Space Station, the researchers built up a comprehensive depiction of how reduced gravity influences the various immune cells present in peripheral blood; these immune cells, notably lymphocytes and monocytes, play pivotal roles in the body’s defense mechanisms.

Excitingly, the study has potential implications for immune aging on Earth, as the changes observed during the aging process parallel those documented during space travel.

Additionally, the paper discusses a pathway for the identification of compounds capable of counteracting the effects of zero gravity, demonstrating that quercetin, one such compound, holds considerable promise not only for mitigating the damaging impacts of spaceflight, but for addressing immune dysfunction during normal aging on Earth [1].

Associate Professor David Furman, PhD is a co-senior author on the new paper

“Our work provides a resource to better understand how and why the immune system changes in simulated microgravity and spaceflight,” said Associate Professor David Furman, PhD, co-senior author. “We also provide a way to develop countermeasures to maintain normal immunity under these harsh conditions.”

Astronauts in a low Earth orbit, such as those aboard the International Space Station, frequently experience immune system challenges, including heightened susceptibility to infections, reactivation of latent viruses and increased skin sensitivity; these adverse reactions manifest even during short-term spaceflights.

Previous investigations, employing both actual and simulated microgravity conditions, have identified impaired functionality in various immune cells. However, the researchers noted that the underlying mechanisms, genes and pathways contributing to immune dysfunction under microgravity remained largely obscure, and so this latest research sought to pin down the cellular-level changes that precipitate these immunological changes.

The research team investigated how 25 hours of simulated microgravity affects the human peripheral blood mononuclear immune system; they used cells from 27 healthy donors aged between 20 and 46, and replicated an environment with minimal gravity by culturing , the cells within a Rotating Wall Vessel, a device engineered by NASA to emulate microgravity conditions.

Employing a variety of techniques, including sequencing and super-resolution microscopy, the team explored the cellular changes induced by reduced gravity. They subsequently validated their findings by comparing their data with results from other space studies conducted on humans and mice, including the JAXA Cell-Free Epigenome study mission, SpaceX’s Inspiration 4 mission, NASA’s Twins Study and analyses of spleens from mice aboard the International Space Station.

Associate Professor Daniel Winer, MD, is also a co-senior author on the Nature Communications paper

“Interestingly, changes in mechanical forces appear to orchestrate immune cell function,” said Winer, whose interest in studying space medicine grew from his exploration of the emerging field of mechanoimmunology, or how environmental forces affect immune cell function. Parts of astroimmunology are related to mechanoimmunolgy, but it is proving its own as a new field, he said, adding that these disciplines are paving the way to better understand how to help the immune system survive in space.

Having unearthed several genes and biochemical pathways influenced by microgravity, the team’s attention moved to trying to identify specific drugs or supplements capable of safeguarding immune cells. To facilitate their search, the team used machine learning technology developed by Furman at the Buck Institute, which is capable of detecting over two million interactions between genes, drugs and various foods.

In their analysis, they identified numerous potential compounds, but focused on quercetin – a plant pigment commonly found in red onions, grapes, berries, apples and citrus fruits – for further exploration due to its widespread availability as an antioxidant and antiaging supplement. The researchers found that quercetin could reverse approximately 70% of the cellular changes induced by microgravity, effectively protecting the cells from excess reactive oxygen species.

“These findings define hallmarks of immune cell alteration in simulated microgravity, with correlation to spaceflight exposures in mice and humans,” said Winer. “This work helps define avenues for future research in mechanoimmunology and astroimmunology and provides opportunities to develop countermeasures to maintain normal cellular function in space.”

Furman said the paper will act as a standard for how to analyze the physiological changes that accompany space travel.

“This is the first comprehensive study that provides the scientific community worldwide with an atlas to understand human biology in this extreme condition,” he said. “The implications are huge, beyond humans in space.”

The researchers are eager to investigate the similar changes seen in aging humans back on Planet Earth, aiming to leverage this knowledge to develop interventions that could potentially address immune dysfunction linked to aging.

[1] https://www.nature.com/articles/s41467-023-42013-y