The final frontier...

The final frontier...

Space is considered the final frontier. When Captain Kirk first led us through the USS Enterprise’s five-year mission to boldly go where no one had gone before, in September 1966, human spaceflight was still very much in its infancy.

Since Russian cosmonaut Yuri Gagarin made the first human spaceflight in April 1961 over 500 humans have flown in space in journeys lasting from 15 minutes to 438 days. After moon landings, extended stays on space stations such as the International Space Station (ISS), we are now also entering the era of space tourism. There are also plans for further space exploration with the NASA Artemis program looking to establish a long-term human presence on the Moon and using the lessons learned for a longer, three-year round trip to Mars sometime in the 2030s.

Beyond the protection of Earth space is a harsh and unforgiving environment. The effects of long duration spaceflight on the human body are complex. Spaceflight exposes astronauts to a wide variety of physiological risks and although the long-term effects of weightlessness and radiation  are not entirely clear there will inevitably be changes, including the cardiovascular system haematological parameters, immunology, the proteome, and microbiome.

When astronauts enter weightlessness (microgravity) conditions, one of the most profound and obvious effects is an immediate decrease in hydrostatic pressure, with fluid is pulled into the upper body and head. There is a shift of around 2L of fluid from the intravascular to intracellular spaces resulting in hypovolaemia with a 10‑15% reduction in circulating blood plasma volume. The fluid shift also leads to a 10% increase in cardiac output. Without the influence of orthostatic pressure and a decrease in arterial pressures the heart works less hard, which is thought to be the cause of the cardiac atrophy seen in astronauts. Increased carotid arterial stiffness and distension has also been observed following long spaceflights. Although the return to gravity results in major discomfort due to orthostatic readjustment the cardiovascular changes generally return to normal.

Experimental evidence for the effects of prolonged exposure to weightlessness and other risks from long-term living in space is not easy to obtain. However, one of the more interesting and unique approaches has been NASA’s “Twins study” [1]. Astronauts Scott and Mark Kelly are monozygotic (identical) twins, and this created the perfect scenario for NASA to study the long-term effects of spaceflight, with Scott spending just under a year (340 days) on the ISS and brother Mark provided the genetically matched Earth‑based control.

The twins were extensively tested for 25 months, before, during and after Scott’s stay on the ISS. Samples of stool, saliva, urine, blood and plasma, peripheral blood mononuclear cells (PBMCs), and sorted immune cells were collected from both subjects and analysed for a comprehensive range of markers. Ten research teams gathered a broad range of comparative data on physiological, telomeric, transcriptomic, epigenetic, proteomic, metabolomic, immune, microbiomic, cardiovascular, vision related, and cognitive changes.

In summary the “Twins study” reported a range of notable outcomes including changes to telomere length, gene regulation, gut microbiome composition, body weight, carotid artery dimensions, and serum metabolites. However the study concluded that most of the biological and human variables remained stable, or at least returned to baseline after completing the mission. That said, in some areas persistent changes lasting longer than six months were noted including to gene expression, increased DNA damage from chromosomal inversions, increased numbers of short telomeres and decline in cognitive function. With the observed persistent molecular changes, for example in gene expression, researchers were unable to predict the consequences of these during multi-year missions.

However, the human body is remarkably resilient and adaptable, and the research suggests that with the right preventative and protective measure astronaut health can be maintained over long missions such as the planned trip to Mars.


1.   Francine E. Garrett-Bakelman et al. The NASA Twins Study: A multidimensional analysis of a year-long human spaceflight.Science364,eaau8650(2019).