The health impacts of NASA's longest-duration human spaceflight are detailed in a new study comparing astronaut Scott Kelly, who spent nearly a year in orbit, with his twin, Mark, back home on Earth. The results point to no significant health differences for Scott, the authors say. However, the results begin to fill in gaps about potential health consequences for astronauts who remain in space longer than six months, though it is unknown if any of the changes that persisted in Scott Kelly upon return to Earth are related to spaceflight alone - or how long they will last. Risks associated with spaceflight include exposure to radiation and microgravity; the way these risks impact health during extended stays in space has been unclear, however. Francine Garrett-Bakelman and colleagues leveraged the opportunity to study this when Scott Kelly spent a year in space aboard the International Space Station (ISS), while his brother, Mark Kelly, former astronaut, remained on Earth as a ground control. Garrett-Bakelman et al. used an integrated multi-omics, molecular, physiological and behavioral approach to evaluate both Kelly brothers before, during and after Scott's year-long ISS mission. Biological samples obtained from Scott while aboard the ISS were either frozen and later shipped or immediately returned to Earth via Soyuz resupply rockets for processing. Analyses identified several changes in Scott compared to his twin, some of which persisted after his time in orbit. Changes included a small (less than five percent) difference in DNA methylation. As well, expression of some of Scott's genes, especially those related to the immune system, changed, though more than 90% of these genes returned to normal expression levels six months after the flight. Changes to the shape of Scott's eyeball, including a thicker retinal nerve, were reported, as well as a decline in some of Scott's cognitive abilities as measured by a series of tests. These changes, emphasize the authors, may not be attributed to space flight alone. The authors also highlight the study's limited sample size. However, towards building a foundational knowledge base for the potential human risks of long-duration spaceflight, Markus Löbrich writes in a related Perspective, "Undoubtedly, the study by Garrett-Bakelman et al. represents more than one small step for mankind in this endeavor."