Tang, GeGeTangPatil, Kaustubh R.Kaustubh R.PatilHoffstaedter, FelixFelixHoffstaedterMore, ShammiShammiMoreEickhoff, Simon B.Simon B.EickhoffJillings, StevenStevenJillingsJeurissen, BenBenJeurissenTomilovskaya, ElenaElenaTomilovskayaGerlach, DariusDariusGerlachNosikova, InnaInnaNosikovaRiabova, AlexandraAlexandraRiabovaPechenkova, EkaterinaEkaterinaPechenkovaPetrovichev, ViktorViktorPetrovichevRukavishnikov, IlyaIlyaRukavishnikovMakovskaya, LyudmilaLyudmilaMakovskayaVan Ombergen AngeliqueWuyts, FlorisFlorisWuytsZu Eulenburg Peter2026-04-232026-04-2320262373-8065https://imec-publications.be/handle/20.500.12860/59165Our study investigates the effects of long-duration spaceflight on brain aging in spacefarers using structural MRI and machine learning models. Pre-, post-, and follow-up scans of ROS cosmonauts ESA astronauts, and matched Earth-bounding controls were analyzed. We found a considerable difference between the spacefareres and the control group, especially in the ESA cohorts (ß = 0.63). In the ROS cohorts, we observed a difference between the pre- and post-flight scans. A post-hoc analysis revealed that the pre-flight brain age delta was 0.842 years less than the immediate post-flight brain age delta after long-duration spaceflight. All three machine learning models showed good to excellent intraclass correlation coefficients (ICC) between the two consecutive MRI sessions. Our findings suggest that long-duration spaceflight may have an effect on human brain aging as observed from MRI.engJournal article10.1038/s41526-026-00575-3WOS:001715851300001MEDLINE:41708639