With the extension of the deep space exploration program, the boundaries of human
exploration will be pushed forward to the surface of Mars. Over the past nearly 60
years manned spaceflight and experimental findings demonstrated that spaceflight induced
bone loss, muscle atrophy, cardiovascular remodeling and space-related medical problems
(Durante and Cucinotta, 2008). There are some long-term spaceflight missions planned
to implement in the next decades, however, health risks and protections from spaceflight
exposures are incompletely clear and still remain a primary concern for manned deep
space explorations (Zhao et al., 2018; Wang et al., 2019). Although more than 560
people have the spaceflight experience, only four individuals have participated in
long-term spaceflight missions lasting 1 year or more (Stepanek et al., 2019). There
is an urgent need to better understand the hazards of long-term spaceflight environment,
including weightlessness, ionizing radiation, confinement, disrupted circadian rhythm
etc.
Recently, one work published in Science (Garrett-Bakelman et al., 2019) showed a systematic
biomedical research of the NASA Twins Study and health risk assessments during a 1-year
mission onboard the International Space Station (ISS). The use of twin model is an
excellent experiment design with the improved reliability and authenticity of the
obtained data from this small sample experiment. As compared to his twin on the earth,
the astronaut living in space presented some changes in telomeres, DNA damage and
methylation, immune, microbial, mitochondrial, cardiovascular, body mass and nutrition,
neuro-ocular, cognitive performance. First, the authors found that the telomere unexpectedly
elongated during spaceflight and distribution toward increased numbers of longer telomeres,
which was soon shortened after returning to the earth. And, the increased average
telomere length was in accordance with the methylation changes of TERT promoter, the
regulatory subunit of telomerase, supported by gene expression, correlated with reduced
body mass and increased serum folate levels inflight. However, it is still unknown
whether the elongated telomeres imply a higher risk of disease occurrence (Helby et
al., 2017). Chromosome aberrations were also analyzed to evaluate potential telomere-related
instability and DNA damage response to ionizing radiation exposures, and the results
showed that the inversion frequencies of inflight twin increased at a greater rate
than translocations, which are consistent with the physical dose of 76.18 mSv and
an effective dose of 146.34 mSv recorded by NASA. Moreover, subtle alternations in
the global and local DNA methylation levels and entropies discordances were observed
in CD4 and CD8 lymphocytes by the methods including the principal components analysis
and genome-wide JSD analysis, etc., and the genes according to the epigenetic discordances
were therefore ranked and conducted by the gene ontology enrichment analysis. Furthermore,
differential gene expression analysis and cytokine data of inflammation signatures
clearly showed many immune-related pathways were significantly influenced and inflammatory
status was increased significantly during inflight. This adds the weights to support
that the space radiation and weightlessness in spaceflight can induce the significant
changes in the DNA damage and inflammation (Sridharan et al., 2015; Chakraborty et
al., 2018).
It was of interesting to find out that a series of mitochondria-related changes were
identified by integrated analysis, including increased basal respiration and decrease
of ATP reserve of plasma, higher level of lactic acid indicating a shift from aerobic
to anaerobic metabolism. Previous works also suggested that energy imbalances potentially
lead to changes with protein metabolism that ultimately impair the immune system (Chakraborty
et al., 2014). In accordance with previous NASA reports, recent evidences showed 29%
visual impairment of short-term spaceflight astronaut and 60% of long-duration mission
crew (Marshall-Goebel et al., 2017). Spaceflight resulted in ocular change and retinal
edema formation of spaceflight twin, including shape change, thickened retinal nerve,
folds appeared in the choroid layer, but not occur in ground control. This space-associated
neuro-ocular syndrome (SANS) was caused by fluid headward shift (Lee et al., 2018),
which also leads to the distension of the neck’s jugular vein, more cardiac output
and a thickening of the forehead’s skin.
Finally, the researchers systematically classified the influenced key physiological
processes into 1) potentially low risk, 2) moderate risk and unknown risk, 3) potentially
high risk. The SASN, cardiovascular physiology, postflight stress and inflammatory
response, genomic instability and dysregulated gene expression were considered as
potentially high risks (Fig. 1). In general, such a risk classification is of great
significance for the disease risk estimations of astronauts in spaceflight, however
further analyses by the quantitative methods are needed to assess the health risk
accurately for deep space exploration missions.
Figure 1
Systematic biomedical research of the NASA Twins Study. Study design, experimental
information and classification of the putative health risks for future human spaceflight.
This study lasted over 25 months, including time points before (preflight), 0–6 month
flight (early flight), 7–12 month flight (late flight) and after (postflight) spaceflight.
TW (flight subject), HR (ground subject). This risk classification is of great significance
for the disease risk estimations of astronauts in spaceflight
Taken together, this twin spaceflight study embodied an investigation trend to deeply
evaluate the risk of more than 1-year long-term manned spaceflight: 1) Systematic
multidimension analysis; 2) Multicenter joint analysis; 3) Interactive verification
analysis of multi-data to improve the reliability and authenticity because of small
samples; 4) Mutual regulation among organs or tissues; 5) Energy metabolism variation
analysis. However, there are large challenges on the integration analysis of the multidimensional
data with the features of limit individuals and time series. Therefore, more effective
data-mine methods are needed for the analysis of these complex datasets. Nevertheless,
this study provides a theoretical and data reference for the subsequent study of human
space flight, and is of landmark significance in the field of space medicine.