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Molecular Changes Wrought by Spaceflight Explored in Newly Published Studies

NEW YORK — Spaceflight exerts increased pressure on the human body, with effects on telomere length, mitochondrial function, and more, a collection of new studies has found.

The NASA Twins Study, published last year, explored the molecular changes caused by spaceflight by comparing samples collected from Scott Kelly, as he spent a year on the International Space Station, to his twin brother Mark Kelly, who stayed Earth-bound. That analysis found that Scott Kelly's telomeres lengthened while in space, though they then shortened upon his return home, and that he experienced gene expression changes, particularly of immune-related genes.

In a suite of new studies appearing in Cell, Cell Reports, and other journals, researchers have built on that study to generate a deeper picture of how spaceflight affects the human body on the molecular level. While they confirmed findings from the NASA Twins Study, the new papers further underscored the role of oxidative and mitochondrial stress in the effect of spaceflights on the body, and point to possible ways to mitigate those effects, which could enable longer missions in space, including to Mars.

"It's a turning point in space biology and aerospace medicine," Christopher Mason, a co-author on many of the studies from Weill Cornell Medicine, said in a statement. "We can start thinking at the molecular and cellular level about longer-term missions, and also what drugs, countermeasures, and therapies could be tried to minimize the risks for astronauts."

In one of the new studies, researchers led by Colorado State University's Susan Bailey compared the telomeres of 11 astronauts before, during, and after their missions at the ISS. In general, the astronauts had shorter telomeres both before and after their time in space than age- and sex-match controls who remained on Earth.

As in the Twin Study, these astronauts' telomeres lengthened while they were in space, as the researchers wrote in their Cell Reports paper. They also noted that the oxidative stress the astronauts experienced was correlated with the lengthening of their telomeres. Their telomeres then rapidly shorted upon their return to Earth.

The researchers also examined the telomeres of individuals who climbed Mount Everest, who also experience oxidative stress. The two climbers they analyzed also had longer telomeres shortly after they reached the summit of the mountain than they did at baseline. Based on this, Bailey and her colleagues suggested that the telomerase-independent alternative lengthening of telomeres (ALT) pathway is activated under these stressful conditions.

Meanwhile, NASA's Afshin Beheshti used data from 59 astronauts and the space agency's GeneLab to uncover other pathways under stress among astronauts due to space flight. GeneLab is a database that aims to help elucidate how DNA, RNA, proteins, and metabolites are all affected by radiation and microgravity to better understand health risks facing astronauts by collecting omics data on model organisms and people who've flown in space.

Their analysis, found in Cell, indicated that mitochondrial pathways are affected by spaceflight and that these, in turn, affect innate immunity, inflammation, cell cycle, circadian rhythm, and olfactory functions. They further validated this finding of increased mitochondrial dysfunction during spaceflight using data from the NASA Twin study. According to the researchers, these findings are further bolstered by other reports of oxidative stress — which is closely tied to mitochondrial dysfunction — being induced by spaceflight. 

Additionally, Beheshti and his colleague examined a microRNA signature associated with spaceflight, and validated it in a combination of rodent and human cell models exposed to radiation and microgravity simulations, as well as in samples from astronauts, as they noted in a separate publication in Cell Reports.

The signature, the researchers noted, could be broken down into two components. MiRNAs like let-7a-5p, let-7c-5p, and miR-223-3p are, for instance, more closely linked to microgravity response, while others are associated with radiation response or are expressed more broadly.

In addition to reflecting cellular pathways affected by spaceflight, the signature also suggests ways the negative effects of spaceflight on the human body might be mitigated. For instance, the researchers found that antagomirs inhibiting miR-125, miR-16, and let-7a, which have also been tied to space-radiation-induced cardiovascular damage, could limit microvascular damage in vitro

In another Cell Reports paper, Weill Cornell's Mason and his colleagues examined clonal hematopoiesis, which is a risk factor for hematological cancers and heart disease, using NASA Twin Study data. They uncovered mutations within the twins linked to clonal hematopoiesis, but at an earlier age than typically expected, suggesting astronauts may need to be monitored over time for clonal hematopoiesis.

Mason and his lab have received two grants from NASA and support from the WorldQuant Foundation to expand their analysis to include banked blood samples from astronauts, as well as to monitor retired astronauts, collect new astronaut samples, and collect samples from patients undergoing radiotherapy and controls. With these, they plan to study not only clonal hematopoiesis, but also gene expression shifts, telomere and genome structure changes, epigenetic alterations, and more over the next 10 years.

A number of other studies appearing today investigated other aspects of space's effect on humans, including on skeletal muscles, cardiac function, and more. Ultimately, the scientists said that these studies and subsequent ones could inform longer-duration space travel, such as missions to Mars. Mason noted in an email that omics-based metrics, alongside others like cognitive and behavioral assessment, will become part of the standard health and physiological assessments that are conducted before, during, and after spaceflight, and that he and his colleagues have laid out a 500-year plan to continue these studies.

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