First long-term study into health of Apollo crews shows deep space missions might take their toll, exposing astronauts to blood vessel-damaging radiation 
 
 Travelling to the moon, Mars or beyond could dramatically increase an astronaut’s risk of dying from cardiovascular disease, the first research into the long-term health of Apollo spacemen has revealed. 
 
 Nasa’s Apollo programme sent nine manned missions and 24 astronauts beyond low Earth orbit during the 1960s and early 1970s, including Apollo 11, which delivered Neil Armstrong and Buzz Aldrin to the moon. But it seems such missions might have taken their toll. 
 
 A team of researchers looking into the fate of the Apollo astronauts has discovered that their rate of death from cardiovascular disease is four to five times higher than that seen for astronauts of the same era who only flew in low Earth orbits, or who never flew on an orbital mission at all. 
 
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 That, the researchers say, suggests that venturing beyond the Earth’s protective magnetic field could cause long-lasting damage to the cardiovascular system, potentially as a result of exposure to deep space radiation. 
 
 The findings come as a number of space agencies and commercial enterprises are looking to venture to the moon and beyond, with Nasa planning to send humans to Mars in the 2030s. 
 
 “With all of these plans for going into deep space we have only had this one really small group [of Apollo astronauts] that has actually done it,” said Michael Delp, first author of the study from Florida State University. “Previous to this study nobody had ever looked at their long-term health consequences - really pulling out the Apollo astronauts out of the group of other astronauts.” 
 
 Jeff Hoffmann, former Nasa astronaut and director of the Man Vehicle Lab at the Massachusetts Institute of Technology, agreed, adding that when it comes to travelling to the moon and beyond, the findings suggest speed might be of the essence. 
 
 “We can’t shield against high energy cosmic radiation, not with our current mass-limiting capabilities, but it does re-emphasise the importance of getting to Mars as quickly as possible,” he said. “The less time you spend in deep space the less exposed you are getting to the radiation.” 
 
 Writing in the journal Scientific Reports, a team of researchers including scientists from Johnson Space Centre and Nasa Ames Research Centre describe how they compared the causes of death for the seven Apollo astronauts who had died up to that point with those of 35 low Earth orbit astronauts from the same era, and 35 non-flight astronauts. 
 
 While the sample size is tiny - a clear limitation to the study - the results reveal that 45% of the Apollo astronauts died from cardiovascular disease, compared to only 9% of non-flight astronauts and 11% of low Earth orbit astronauts. 
 
 While no difference was seen when the rate was compared to that of the general population, Delp believes that is most likely because astronauts are very fit and healthy, whereas the members of the public suffer from a wide range of conditions that could increase their risk of cardiovascular disease. 
 
 “Part of the reason why this cardiovascular effect has never been uncovered is because you are always looking and comparing [astronauts with] a general population,” he said. 
 
 To probe whether deep space radiation might be behind their findings, the researchers exposed mice to conditions that simulated weightlessness as well as the radiation found in deep space. 
 
 With previous studies showing that both radiation and weightlessness can, in the short term, damage the blood vessels of the mice, the researchers waited 6-7 months before investigating the effects - a period equivalent to around 20 human years. 
 
 The results revealed that while weightlessness did not cause any lasting cardiovascular harm, the radiation did. Mice exposed to radiation were found to have sustained damage to the cells lining their blood vessels - damage that could increase the risk of cardiovascular disease. 
 
 The fact that, by contrast, weightlessness caused no lasting damage makes sense, says Delp. “That corresponds with what we saw with the low Earth orbit [astronauts] - they may have problems immediately when they come back, which we know they do, but they recover.” 
 
 Richard Hughson, of the University of Waterloo in Canada, who has studied the effect space travel on the cardiovascular systems of astronauts, described the new research as “fascinating”. 
 
 While Hughson notes that the sample size for the Apollo lunar astronauts is very small, he believes the study puts forward a plausible suggestion for why lunar astronauts appear to be succumbing cardiovascular disease at a higher than expected rate. 
 
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 “I think it is really important that Nasa and the European Space Agency, the Canadian Space Agency, and so on, recognise now that the cardiovascular system should be an important focus, one they look at, when they send astronauts beyond low Earth orbit,” he said. 
 
 With only an ultrasound device and a blood-pressure test needed to check for damage to the lining of the blood vessels, Hughson believes astronauts could monitor the effects of the radiation during their time in deep space, while the results also flag the importance of checking up on the cardiovascular health of astronauts once their have returned to Earth. “We just did this within the last month on Tim Peake when he came back from space,” he said. 
 
 Hoffman agrees that such check-ups are important. “I go down to Nasa every year for a thorough physical examination and if they know that cardiovascular fitness is important, that is something they can monitor you for every year and hopefully reduce the risk of a premature death from heart problems,” he said. 
 
 Delp admits that a deeper look into the medical history of the Apollo astronauts is needed to make sure that the findings are not the result of other factors - including their somewhat eclectic post-mission lifestyles. But, he adds, the new research also raises further conundrums, from the radiation doses needed to damage the cardiovascular system to whether the effects differ between the sexes and whether the problem can be lessened. 
 
 “All of these are future questions that really I think are important to address before we start sending humans into deep space again,” he said. ||||| Breaking News Emails Get breaking news alerts and special reports. The news and stories that matter, delivered weekday mornings. 
 
 / Updated By Samuel Sarmiento, MD 
 
 The Apollo astronauts — the first men to land on the moon — took a giant leap for mankind. But the deep space radiation that dosed the men who left the Earth's orbit may have damaged their hearts, according to a new study published Thursday in the journal Science. 
 
 The number of deaths due to heart disease among the Apollo lunar astronauts is almost five times greater than that in non-flight astronauts, or astronauts who never flew missions in space, researchers from Florida State University found. Compared to astronauts who flew only in low Earth orbit (LEO), the heart risk among Apollo astronauts is four times higher. There were no differences between LEO and non-flight astronauts. 
 
 Apollo was a NASA program that made 11 total space flights between 1968 and 1972, six of them landed on the moon. Twelve men, including Neil Armstrong and Edwin E. “Buzz” Aldrin, walked on the lunar surface. 
 
 Astronaut Edwin E. Aldrin Jr., lunar module pilot, walks on the surface of the moon near a leg of the Lunar Module during the Apollo 11 extravehicular activity (EVA). Astronaut Neil A. Armstrong, Apollo 11 commander, took this photograph with a 70mm lunar surface camera. The astronauts' bootprints are clearly visible in the foreground. While astronauts Armstrong and Aldrin descended in the Lunar Module (LM) "Eagle" to explore the Sea of Tranquility region of the moon, astronaut Michael Collins, command module pilot, remained with the Command and Service Modules (CSM) "Columbia" in lunar orbit (Photo Credit: NASA). NASA 
 
 Apollo astronauts are different 
 
 Unlike astronauts in other space missions, Apollo lunar astronauts are the only humans to have traveled outside of the Earth’s geomagnetic field and into deep-space. They went outside of the earth’s protective “magnetosphere” — the region surrounding the planet where its own magnetic field dominates. The magnetosphere causes galactic cosmic rays and solar particles to detour around the Earth. 
 
 Exposure to this radiation in deep-space is what may account for the increased heart problems in the Apollo astronauts. 
 
 “We’ve probably underestimated the impact of deep-space radiation on not just cardiovascular disease but health in general”, said lead author of the study, exercise physiologist Dr. Michael Delp of Florida State University. 
 
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 Of the 24 Apollo astronauts who flew around the moon on nine missions, eight have died. Of the 7 included in the study, 43 percent died from cardiovascular disease. Other causes of death included cancer (29 percent) and accidents (14 percent). Edgar Mitchell, the 6th man to walk on the moon, died in February but wasn’t included in the study. 
 
 Conditions encountered in space have been found to affect men and women differently. For instance, weightlessness can lead to a problem regulating blood pressure known as orthostatic hypotension, which is more common among female astronauts. In the new study, although there were some females among the flight and non-flight astronauts, everyone who died from heart disease was male. 
 
 RELATED: After a heart attack, how much time does the patient have to get treated? 
 
 According to Delp, more research is still needed to better understand these differences. 
 
 It's known that space exploration comes with many health risks, including brittle bones, balance issues, and heart problems. 
 
 But in previous research, the astronauts — who are in peak physical condition — were compared to the general population. 
 
 The Florida State research is the first comparison of the health of astronauts with other astronauts, based on the type of their mission. The study looked at the long-term effects of simulated weightlessness and radiation on the blood vessels of mice. 
 
 The researchers found that, unlike weightlessness, the effect of radiation on blood vessels is sustained. These changes occur in the lining of the blood vessels and can initiate or accelerate coronary heart disease. 
 
 NASA released a statement responding to the study's findings: “It is not possible to determine whether cosmic ray radiation affected the Apollo astronauts. Limitations of the study include the small number of astronauts in the Apollo program and lifestyle factors that cannot be quantified -- such as family genetics and diet.” 
 
 The new study could spark more research specifically looking at this before embarking on other deep-space mission to the moon or Mars in the near future. ||||| Life on Earth is insulated from the harmful effects of galactic cosmic rays and solar particle events through particle deflection by the Earth’s magnetosphere and shielding by Earth’s atmosphere. With the exception of the Apollo lunar missions, manned spaceflight has taken place exclusively in LEO where atmospheric protection from space radiation is essentially absent, but protection by the Earth’s geomagnetic field is present. Under these conditions, it has been broadly assumed that missions in LEO or short excursions to the Moon would not increase the long-term risk for CVD among astronauts16,18. Using non-flight astronauts as a comparison group, the data show that this group had a mortality rate of approximately 9% due to CVD (Fig. 1). The mortality rate for CVD among all US flight astronauts, including both LEO and Apollo lunar astronauts, was not different than that in the non-flight astronauts. However, when considered as a separate group, the Apollo lunar astronauts, the only group of humans to have traveled outside of the Earth’s protective magnetosphere, demonstrate a higher mortality rate due to CVD compared to both the cohort of astronauts that did not travel into space, as well as astronauts who remained in LEO (Fig. 1). These data suggest that human travel into deep space may be more hazardous to cardiovascular health than previously estimated. 
 
 Astronaut mortality has been reported in four previous studies. In the first by Peterson et al.22, it was reported that of the 20 deceased US astronauts from 1959–1991 the causes of death were due to circulatory disease (10%), cancer (5%), accidents (80%) and other causes (5%). Using the US population as the reference group, it was found that mortality due to CVD was significantly lower in astronauts and accidental deaths were significantly higher22. A subsequent study by Hamm et al.23 focused solely on cancer-specific mortality among astronauts through 1995, and included an additional reference group of Johnson Space Center employees. This comparison group was part of a Longitudinal Study of Astronaut Health initiative by the National Aeronautics and Space Administration (NASA) to better assess the occupational health risks of astronauts, since the health characteristics of astronauts and the overall environment in which they train at Johnson Space Center were deemed to be different from that of the general US population24. Results from this study indicated that there was not a significant difference in cancer mortality between astronauts and Johnson Space Center employees or Texas residents living in the area surrounding Johnson Space Center23. In a follow-up study by Hamm et al.25, cause-specific mortality rates beyond just cancer were examined. The only significant difference found was a higher number of accidental deaths among astronauts (69%) relative to Johnson Space Center employees (14%). Finally, in the most recent study published by Reynolds and Day26, the cause-specific mortality rates from 1980–2009 were reported in astronauts and residents of Harris County, Texas, where Johnson Space Center is located. The results indicated a lower risk of death due to CVD and cancer in astronauts versus Harris County residents, and a higher risk of death due to accidents26. Collectively, these studies indicate that the risk of death due to chronic diseases appears to be lower in astronauts, particularly those involving CVD22,26. 
 
 The current analysis of mortality rates among astronauts differs from these previous studies in several important ways. The first is the reference population used to gauge the significance of cause-specific mortality rates among astronauts. The biomedical characteristics of astronauts are very different from individuals in the general population. According to the Review of NASA’s Longitudinal Study of Astronaut Health by the Institute of Medicine24, astronauts have substantially higher incomes, levels of education, general fitness, and lifelong access to medical care, all of which are factors known to contribute to high levels of health and well-being. With such large baseline differences between astronauts and comparison groups, it is difficult to ascertain what specific impact spaceflight might have on astronaut health. For this reason, the Institute of Medicine recommended in 2004 that astronauts who have never flown in space be used as a reference population24; the present study is the first to incorporate non-flight astronauts as a comparison group. Consequently, current results demonstrate that previous conclusions suggesting the risk of death due to CVD is lower among flight astronauts22,26 are no longer tenable. 
 
 The second unique feature of the present study is that it is the first to examine the long-term mortality risks of spaceflight in LEO and deep space. Exposure to charged particles comprising the galactic cosmic rays in deep space has the potential to elicit a number of complications in biological tissue. Recent work in rodents and cell culture has highlighted the potentially harmful effects of such exposures on the cardiovascular system20,27,28,29,30, which may translate to astronauts engaged in deep space expeditions. 
 
 While traveling from LEO to the Moon and back, the Apollo lunar astronauts traversed regions of geomagnetically trapped electrons and protons known as the Van Allen belts and, depending on the duration of their mission and the specific activities in which they were engaged (e.g., lunar surface and intravehicular Command and Lunar Module activities), were continuously subjected to varying levels of high-energy cosmic rays31. Fortunately, there were no major solar particle events during any of the Apollo missions. The lunar astronauts also experienced a visual phenomenon of light flashes (~17/hour) when the spacecraft was dark, and tests indicated that the flashes were the result of HZE cosmic rays traversing the retina31,32. 
 
 Interactions of the galactic cosmic rays with the spacecraft hull will have a large impact on the radiation exposure of astronauts. Charged particles traversing the hull or “shielding” of the ship will incur nuclear interactions that depend on the composition and thickness of the hull material. These interactions will result in fragmentation products and particles of reduced energy but higher LET that contribute to the radiation dose within the spacecraft. The average radiation dose for the seven deceased Apollo crew was 0.59 ± 0.15 cGy (range 0.18–1.14 cGy)31. If we assume representative shielding scenarios (10 g/cm2) for the Apollo Command Module and radiation quality factors drawn from the most recent International Commission on Radiological Protection33, then the average radiation dose from the galactic cosmic rays to the Apollo astronauts would be approximately 0.295 cGy, or roughly half the total dose during their lunar excursions9. Using similar assumptions, astronauts in LEO would receive 50–100 mSv over a 6–12 month stay, of which the galactic cosmic rays would account for approximately two-thirds of this total dose9. Thus, given their mean mission duration of 15.6 days, the deceased LEO astronauts would receive approximately 0.29 cGy, a galactic cosmic ray dose very similar to the Apollo lunar astronauts. 
 
 Despite virtually identical estimates for galactic cosmic ray exposure, the mortality rate of LEO astronauts for CVD is significantly lower than in Apollo lunar astronauts. Furthermore, LEO astronauts do not exhibit significant differences in mortality compared to non-flight astronauts. Several factors may account for this apparent paradox. First, lunar and LEO galactic cosmic ray dose estimates were made using certain assumptions that are constantly being revised. For instance, if actual shielding levels for the Apollo missions were less than 10 g/cm2, calculated lunar galactic cosmic ray doses may be underestimates. Second, activities on the lunar surface and inside the lightly shielded Lunar Module may also include dose contributions from scattered albedo neutrons, which are relatively insignificant inside a spacecraft. And finally, lunar and deep space exposures will include dose contributions from less energetic and lighter particles. For astronauts in LEO, the relative contribution of particles with energies below the geomagnetic cutoff is lower since they will be deflected by the Earth’s magnetosphere. While it remains uncertain whether differences in absorbed dose profiles can account for the elevated lunar CVD mortality rates reported here, it is equally difficult to disregard this possibility. As a result, these findings highlight the potential adverse impact of charged particles and their unique microdosimetric properties on post-mitotic cellular structures responsible for maintaining longer-term cardiovascular health. 
 
 The possibility of long-term degenerative effects of deep space travel on cardiovascular function has not been well described or substantiated. Only in the last decade, when multiple spacefaring nations and corporate entities have announced plans to embark on manned exploratory missions to Mars and prolonged habitation on the Moon, has biomedical research been directed towards identifying possible CVD risks associated with the deep space radiation environment. Consequently, there is limited information available on the effects of charged particle HZE radiation on the cardiovascular system. 
 
 Results from the present study address the question of possible long-lasting interactive effects of simulated weightlessness and space radiation on vascular function. To experimentally address this question, vascular responses of resistance arteries were determined 6–7 months after the cessation of a 14-day hindlimb unloading treatment, a 1 Gy 56Fe irradiation treatment, or a treatment consisting of a combination of the two. Given that the average life-span of male C57BL/6 mice is 878 ± 10 days34, the 6–7 month period represents approximately 23% of animals’ life or roughly the equivalent of 18–20 years in humans. The data show that hindlimb unloading alone had no persistent effect to significantly diminish endothelium-dependent vasodilation, while HZE irradiation alone and in combination with unloading impaired endothelium-dependent vasodilation (Fig. 2) through the NO signaling mechanism (Fig. 3). This decrement in NO signaling appears to be mediated primarily through greater NO scavenging by reactive oxygen species, as evidenced by higher vascular protein content (Fig. 5A,B)20,27 and activity27 of XO in peripheral and coronary arteries. These data indicate that the long-lasting effects of simulated weightlessness and space radiation on vascular endothelial function are the result of the radiation exposure and are not due to an interaction with weightlessness. As dysfunction of the vascular endothelium is central to the pathogenesis of vascular disease35,36, such adverse arterial effects could lead to the development of occlusive arterial diseases, including myocardial infarction and stroke. 
 
 Although results from the present study provide new evidence that even short-term spaceflight beyond the Earth’s protective magnetosphere may have adverse effects on CVD mortality, there are limitations to consider. First, the sample size for cause-specific deaths among lunar astronauts is small. Therefore, caution must be used in drawing definitive conclusions regarding specific health risks. Second, although deep space radiation seems a likely cause underlying the higher proportional mortality rate due to CVD in Apollo astronauts, it remains unknown what specific factor(s) in the space environment is responsible. And third, although the HZE irradiation used in the animal studies was selected to mimic that which deep space travelers might encounter, the absorbed dose (1 Gy) and the dose rate (single exposure, 10cGy/min) would be higher and faster than that experienced by the Apollo lunar astronauts31. It would be more representative of the space environment to have the radiation exposure occur at a lower dose rate and over an extended time period. Unfortunately, that type of exposure paradigm using 56Fe ions is not currently feasible at Brookhaven National Laboratory. Despite these limitations, results from these animal studies demonstrate that space relevant irradiation induces long-lasting vascular dysfunction of the type known to presage the development of atherosclerotic cardiovascular disease35,36. 
 
 In summary, results from the present study reveal that Apollo lunar astronauts have a significantly higher mortality rate due to CVD than either the cohort of astronauts who never flew an orbital space mission or astronauts who never flew beyond LEO (Fig. 1). Moreover, the CVD mortality for lunar flight astronauts was higher than that in the age-matched US population, although this difference was not statistically significant. These findings suggest that in spite of the “healthy worker” effect, short-duration deep space travel by this highly educated, trained and physically fit group results in a significantly elevated risk of death from CVD. The major environmental factor that would appear to underlie this phenomenon is deep space radiation. Estimates indicate that the dose of galactic cosmic ray irradiation to which LEO and lunar astronauts were exposed were not greatly different. However, qualitative differences in the absorbed dose profiles resulting from the effect of the Earth’s magnetosphere to deflect less energetic and lighter galactic cosmic ray particles away from Earth may account for the lower CVD mortality rate among LEO astronauts. Animal studies also indicate that while simulated weightlessness and space-relevant irradiation interact to induce early impairment of endothelium-dependent vasodilation20, the only sustained vascular endothelial cell dysfunction is that mediated by exposure to HZE particles and not by simulated weightlessness (Fig. 2). If such results translate to the human condition, then long-term dysfunction of the vascular endothelium induced by charged HZE particles could be a major contributor to the development of atherosclerotic cardiovascular disease in astronauts.
– Planning a trip to the moon? You might want to think about heart health first. According to a study published in Scientific Reports, travel in deep space dramatically raises the risk of cardiovascular disease. Florida State University researchers looked at America's Apollo astronauts, who are the only people ever to have gone to deep space, and found that they were four to five times more likely to die of cardiovascular disease than other astronauts, NBC News reports. Eight of the 24 Apollo astronauts have died, and of the seven deaths looked at, three, including Neil Armstrong, were from cardiovascular disease. That works out to roughly 45%, compared with around 10% among astronauts who either remained in low Earth orbit or never went to space at all. The study suggests that leaving the Earth's protective magnetosphere, which deflects cosmic radiation, even for short periods can do long-term damage to the cardiovascular system, according to the researchers. They say that since astronauts are selected from some of the most physically fit people around, the link wasn't uncovered until the Apollo crews were compared to other astronauts instead of the general public. Former NASA astronaut Jeff Hoffman says the implications are clear: Space travel needs to be fast. "We can't shield against high-energy cosmic radiation, not with our current mass-limiting capabilities, but it does re-emphasize the importance of getting to Mars as quickly as possible," he tells the Guardian. (Last month, NASA started an experimental fire on a cargo vessel.)