1
RESEARCH ARTICLE SUMMARY HUMAN PHYSIOLOGY The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight Francine E. Garrett-Bakelman et al. INTRODUCTION: To date, 559 humans have been flown into space, but long-duration (>300 days) missions are rare (n = 8 total). Long-duration missions that will take humans to Mars and beyond are planned by public and private entities for the 2020s and 2030s; therefore, comprehensive studies are needed now to assess the impact of long-duration spaceflight on the human body, brain, and overall physiology. The space environment is made harsh and challenging by multiple factors, including confinement, isolation, and exposure to environmental stressors such as microgravity, radiation, and noise. The selec- tion of one of a pair of monozygotic (identical) twin astronauts for NASAs first 1-year mission enabled us to compare the impact of the space- flight environment on one twin to the simulta- neous impact of the Earth environment on a genetically matched subject. RATIONALE: The known impacts of the space- flight environment on human health and per- formance, physiology, and cellular and molecular processes are numerous and include bone density loss, effects on cognitive performance, microbial shifts, and alterations in gene reg- ulation. However, previous studies collected very limited data, did not integrate simulta- neous effects on multiple systems and data types in the same subject, or were restricted to 6-month missions. Measurement of the same variables in an astronaut on a year-long mis- sion and in his Earth-bound twin indicated the biological measures that might be used to determine the effects of spaceflight. Presented here is an integrated longitudinal, multidimen- sional description of the effects of a 340-day mission onboard the International Space Station. RESULTS: Physiological, telomeric, transcrip- tomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision- related, and cognitive data were collected over 25 months. Some biological functions were not significantly affected by spaceflight, including the immune response (T cell recep- tor repertoire) to the first test of a vaccination in flight. However, significant changes in multiple 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. These included changes in telomere length, gene regulation measured in both epigenetic and transcriptional data, gut microbiome compo- sition, body weight, carotid artery dimensions, subfoveal choroidal thickness and peripapillary total retinal thickness, and serum metabolites. In addition, some factors were significantly af- fected by the stress of re- turning to Earth, including inflammation cytokines and immune response gene networks, as well as cog- nitive performance. For a few measures, persistent changes were observed even after 6 months on Earth, including some genesexpression levels, increased DNA damage from chromosomal in- versions, increased numbers of short telomeres, and attenuated cognitive function. CONCLUSION: Given that the majority of the biological and human health variables remained stable, or returned to baseline, after a 340-day space mission, these data suggest that human health can be mostly sustained over this du- ration of spaceflight. The persistence of the molecular changes (e.g., gene expression) and the extrapolation of the identified risk factors for longer missions (>1 year) remain estimates and should be demonstrated with these mea- sures in future astronauts. Finally, changes de- scribed in this study highlight pathways and mechanisms that may be vulnerable to space- flight and may require safeguards for longer space missions; thus, they serve as a guide for targeted 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: [email protected] Cite 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 NASATwins 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 of 25 months (circles indicate time points at which data were collected). (Right) Data were integrated to guide biomedical metrics across various -omesfor future missions (concentric circles indicate, from inner to outer, cytokines, proteome, transcriptome, and methylome). ON OUR WEBSITE Read the full article at http://dx.doi. org/10.1126/ science.aau8650 .................................................. EMBARGOED UNTIL 2PM U.S. EASTERN TIME ON THE THURSDAY BEFORE THIS DATE:

HUMAN PHYSIOLOGY The NASA Twins Study: A …...144 12 APRIL 2019† VOL 364 ISSUE 6436 sciencemag.org SCIENCE The list of author affiliations is available in the full article online

  • Upload
    others

  • View
    0

  • Download
    0

Embed Size (px)

Citation preview

Page 1: HUMAN PHYSIOLOGY The NASA Twins Study: A …...144 12 APRIL 2019† VOL 364 ISSUE 6436 sciencemag.org SCIENCE The list of author affiliations is available in the full article online

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: [email protected] 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).

ON OUR WEBSITE◥

Read the full articleat http://dx.doi.org/10.1126/science.aau8650..................................................

EMBARGOED UNTIL 2PM U.S. EASTERN TIME ON THE THURSDAY BEFORE THIS DATE: