RESEARCH ARTICLE SUMMARY◥

HUMAN PHYSIOLOGY

The NASA Twins Study:A multidimensional analysis of ayear-long human spaceflightFrancine E. Garrett-Bakelman et al.

INTRODUCTION: To date, 559 humans havebeen flown into space, but long-duration(>300 days) missions are rare (n = 8 total).Long-duration missions that will take humansto Mars and beyond are planned by publicand private entities for the 2020s and 2030s;therefore, comprehensive studies are needednow to assess the impact of long-durationspaceflight on the human body, brain, andoverall physiology. The space environmentis made harsh and challenging by multiplefactors, including confinement, isolation, andexposure to environmental stressors such asmicrogravity, radiation, and noise. The selec-tion of one of a pair of monozygotic (identical)twin astronauts for NASA’s first 1-year missionenabled us to compare the impact of the space-flight environment on one twin to the simulta-neous impact of the Earth environment on agenetically matched subject.

RATIONALE: The known impacts of the space-flight environment on human health and per-formance, physiology, and cellular andmolecularprocesses are numerous and include bonedensity loss, effects on cognitive performance,

microbial shifts, and alterations in gene reg-ulation. However, previous studies collectedvery limited data, did not integrate simulta-neous effects on multiple systems and datatypes in the same subject, or were restricted to6-month missions. Measurement of the samevariables in an astronaut on a year-long mis-sion and in his Earth-bound twin indicatedthe biological measures that might be used todetermine the effects of spaceflight. Presentedhere is an integrated longitudinal,multidimen-sional description of the effects of a 340-daymission onboard the International Space Station.

RESULTS: Physiological, telomeric, transcrip-tomic, epigenetic, proteomic, metabolomic,immune, microbiomic, cardiovascular, vision-related, and cognitive data were collectedover 25 months. Some biological functionswere not significantly affected by spaceflight,including the immune response (T cell recep-tor repertoire) to the first test of a vaccinationin flight. However, significant changes inmultiple data types were observed in associ-ation with the spaceflight period; the major-ity of these eventually returned to a preflight

state within the time period of the study. Theseincluded changes in telomere length, generegulation measured in both epigenetic andtranscriptional data, gut microbiome compo-sition, body weight, carotid artery dimensions,subfoveal choroidal thickness and peripapillarytotal retinal thickness, and serum metabolites.In addition, some factors were significantly af-

fected by the stress of re-turning to Earth, includinginflammation cytokinesand immune response genenetworks, as well as cog-nitive performance. Fora few measures, persistent

changes were observed even after 6 months onEarth, including some genes’ expression levels,increased DNA damage from chromosomal in-versions, increased numbers of short telomeres,and attenuated cognitive function.

CONCLUSION: Given that the majority of thebiological andhumanhealth variables remainedstable, or returned to baseline, after a 340-dayspacemission, these data suggest that humanhealth can be mostly sustained over this du-ration of spaceflight. The persistence of themolecular changes (e.g., gene expression) andthe extrapolation of the identified risk factorsfor longer missions (>1 year) remain estimatesand should be demonstrated with these mea-sures in future astronauts. Finally, changes de-scribed in this study highlight pathways andmechanisms that may be vulnerable to space-flight and may require safeguards for longerspace missions; thus, they serve as a guide fortargeted countermeasures or monitoring dur-ing future missions.▪

RESEARCH

144 12 APRIL 2019 • VOL 364 ISSUE 6436 sciencemag.org SCIENCE

The list of author affiliations is available in the full article online.Email: nasa.twins.study@gmail.comCite this article as F. E. Garrett-Bakelman et al., Science 364,eaau8650 (2019). DOI: 10.1126/science.aau8650

Ground Flight

Twins Study Analyses

Integrative Analyses

Results

Subjects

Preflight

Inflight

Postflight

Biochemical

Cognition

Epigenomics

Gene expression

Immune

Metabolomics

Microbiome

Proteomics

Physiology

Telomeres

Multidimensional, longitudinal assays of the NASA Twins Study. (Left and middle) Genetically identical twin subjects (ground and flight)were characterized across 10 generalized biomedical modalities before (preflight), during (inflight), and after flight (postflight) for a total of25 months (circles indicate time points at which data were collected). (Right) Data were integrated to guide biomedical metrics across various“-omes” for future missions (concentric circles indicate, from inner to outer, cytokines, proteome, transcriptome, and methylome).

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