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 by Staff Writers Ithaca NY (SPX) Apr 12, 2019
Long-term spaceflight causes more changes to gene expression than shorter trips, especially to the immune system and DNA repair systems, according to research by Weill Cornell Medicine and NASA investigators as part of NASA's Twins Study, which followed the only set of identical twin astronauts for more than a year. Dr. Christopher Mason, an associate professor of physiology and biophysics at Weill Cornell Medicine, led one of 10 teams of scientists chosen by NASA to compare genetic, physiologic and behavioral changes in identical twins Scott and Mark Kelly before, during and after Scott embarked on a one-year mission on the International Space Station from 2015-2016. Mark, who has gone on shorter space missions in the past, stayed behind on Earth, providing a genetically identical control subject. The findings, which were published April 11th in Science and featured on its cover, show that Scott experienced thickening of the carotid artery, thickening of the retina, weight loss, shifts in gut microbes, reductions in cognitive abilities, DNA damage and changes in gene expression, and a lengthening of the ends of chromosomes called telomeres during the flight. Upon return to Earth, the telomere elongation was replaced by accelerated shortening and loss, a potentially negative consequence for cellular health. The study will help scientists better understand the changes astronauts undergo during long-term space travel. It may also help them better treat or prevent any damage to astronauts' health caused by prolonged spaceflight, particularly as NASA and other groups prepare for three-year missions to Mars. "It gives us a biomedical and molecular road map for future astronauts," said Dr. Mason, who is also an associate professor of computational genomics in computational biomedicine at Weill Cornell Medicine's HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute of Computational Biomedicine, an associate professor of neuroscience in the Feil Family Brain and Mind Research Institute, member of the Sandra and Edward Meyer Cancer Center, and director of the WorldQuant Initiative for Quantitative Prediction. Dr. Mason led the genetic, gene expression, and epigenetic investigations for the study. The 10 teams of investigators, which included co-investigator Dr. Ari Melnick from the Weill Department of Medicine, were selected in March 2014 and had just a few months to prepare the protocols they would use to collect and analyze samples from Scott and Mark. During the mission, Dr. Mason's colleague, Dr. Francine Garrett-Bakelman, then a joint post-doctoral fellow in Dr. Mason and Dr. Melnick's laboratories, collected in Houston the samples of Scott's blood that he sentback to Earth, and analyzed them within 36 hours. The team also looked at samples obtained from Scott and Mark for six months before the trip and for nine months after Scott returned. They were searching for mutations or damage in their DNA and for epigenetic changes that determine which genes are turned on or off. They also looked at changes in the proteins produced by the men's cells to assess how the changes may affect their health. Some of the changes in gene activity, such as those involved in bone formation or DNA repair, were expected since it is well known that astronauts experience reductions in bone density in zero gravity as well as increased exposure to DNA-damaging radiation during the flight. But they also saw changes in the activity of mitochondrial genes, which help the body produce energy, and immune system genes suggesting longer-term travel may increase the stress on the body. Using new methods from the laboratory of Dr. Augustine M.K. Choi, the Stephen and Suzanne Weiss Dean of Weill Cornell Medicine and Cornell's provost for medical affairs, the investigators also observed a higher amount of mitochondrial DNA present in the cell-free DNA fraction of the blood, which is an indicator of cellular stress. "Gene expression changed dramatically," Dr. Mason said. "In the last six months of the mission, there were six times more changes in gene expression than in the first half of the mission." While many of the changes reversed after Scott returned to Earth, a few remained, including cognitive deficits, DNA damage and some changes in T-cell activation. "We don't know yet if these changes are good or bad," Dr. Mason said. "This could just be how the body responds, but the genes are perturbed, so we want to see why and track them to see for how long." The study may also help patients on Earth, particularly those with cancer who often undergo dramatic genetic changes and endure radiation exposure. Studying both a healthy human on Earth in great detail as well as a person exposed to tremendous stressors in space can give scientists new insights into what is a normal response to stress and how much the body can adapt. This may help scientists distinguish the body's normal stress response from pathological changes associated with cancer, infection, or other stressors. "It is likely that these two astronauts have been studied at greater depth than any other person in history," said Dr. Mason, who is also a cofounder, equity stakeholder and consultant for Onegevity Health, a company which provides a comprehensive molecular portrait and customized recommendations for an individual's health based on integrated analysis of longitudinal blood, genetics and microbiome profiles. "They give us a really in-depth view of cellular, molecular and physiological changes that can help us learn what is in the range of what a human can endure." Useful new tools have also emerged from the study, including portable DNA-sequencing techniques created by Dr. Mason's team that will be used by astronauts to sequence their own DNA on future space missions. In 2016, during NASA's year-long Biomolecular Sequencer Mission, Dr. Mason and colleagues demonstrated that DNA sequencers can function on the International Space Station. Building on that finding, Dr. Mason's group in 2019 published a machine-learning algorithm in Nature Communications revealing that the technology can also detect epigenetic changes in space. This work is funded by NASA and the Translational Research Institute for Space Health to help the new set of additional year-long missions on the ISS and to prepare for Mars. The same technology is now being used to help control disease outbreaks, including Ebola in West Africa and Zika in Brazil, by providing a portable sequencing tool that can be used in the field, he said. Through a Cornell Tech start-up called Biotia, for whichDr. Mason is a co-founder and equity holder, the DNA sequencer is also being used in several international hospitals to track infections, helping to pioneer faster DNA testing methods for all hospitals, including in New York City. "You no longer have to wait days or weeks for DNA sequencing and analysis," Dr. Mason said. "You can get it done in a couple of hours, either on Earth or on the International Space Station."
Colorado State University Would Scott Kelly undergo a Benjamin Button or Interstellar-like effect, and return to Earth younger than his brother Mark? Based on preliminary results released in January 2017, Colorado State University Professor Susan Bailey, who studies telomeres, or the protective "caps" on the ends of chromosomes, found that Scott's telomeres in his white blood cells got longer while in space. Changes in telomere length could mean a person is at risk for accelerated aging or the diseases that come along with getting older. Telomeres typically shorten as a person ages. These findings ran counter to what Bailey thought might occur, and are confirmed in "The NASA Twins Study: A multi-dimensional analysis of a year-long human spaceflight," published in Science April 12. To study the twins' telomeres, Bailey and her team received vials of their blood over 25 months, spanning time points before, during and after spaceflight. Her team processed and analyzed the precious samples, delivered fresh from the space station by Soyuz rocket and overnight couriers. "We were surprised, that was the first reaction," said Bailey, when asked how it felt to see the initial findings. "But that's what science is all about, right?" Results from the study have implications for astronauts and people who want to explore space in the years to come through private ventures as humankind ventures longer and deeper in space. NASA has announced plans for a mission to Mars and to a cis-Lunar station (between the Earth and the Moon), which will provide new opportunities for studying what happens to the human body during extended spaceflight.
Twelve universities, more than 80 researchers Among the conclusions, the research teams found: + Scott experienced dramatic shifts in telomere length dynamics, a biomarker that can help evaluate health and potential long-term risks of spaceflight + 91.3 percent of Scott's gene expression levels returned to normal or baseline levels within six months of landing back on Earth (note: this does not mean that the rest of his DNA was mutated, as reported in some stories published last year) + the flu vaccine administered in space worked exactly the same as on Earth + changes in Scott's diversity of gut flora in space were no greater than stress-related changes scientists observe on Earth + proper nutrition and exercise while in space resulted in decreased body mass and increased folic acid, which is vital for making red blood cells, for Scott. Shorter telomeres mean a higher risk for some age-related health conditions Bailey said that from her perspective, "the most striking finding" is the elongation of Scott's telomeres in space. While most of his telomeres returned to near pre-flight averages, he now has more short telomeres than he did prior to the 340-day mission. Having shorter telomeres puts a person at higher risk for accelerated aging, said Bailey. This also increases the risk for diseases that come along with aging, including cardiovascular disease and some cancers. "For us Earthlings, it's pretty similar," Bailey explained. "We all worry about getting older, and everyone wants to avoid cardiovascular disease and cancer. If we can figure out what's going on, what's causing these changes in telomere length, perhaps we could slow it down. That's something that would be of benefit to everybody."
Launching a new research mission In this integrated One-Year Mission Project, she'll study 10 astronauts on one-year missions, 10 on six-month missions, and 10 on trips from two to three months at a time. Health data will be compared with people on the ground who are in isolation for those same periods of time. "We're trying to determine if it is indeed something specific about space flight that is causing the changes we've seen," she explained. NASA's Human Research Program and Space Biology Program funded 25 proposals, all of which will contribute to the space agency's long-term plans, which include human missions to the Moon and Mars. Through these studies, NASA aims to address five hazards of human space travel: space radiation, isolation and confinement, distance from Earth, gravity fields (or lack thereof), and hostile or closed environments that pose great risks to the human mind and body in space.
University of Texas Health Science Center at San Antonio Kumar Sharma, M.D., and Manjula Darshi, Ph.D., from UT Health San Antonio's Center for Renal Precision Medicine, together with Brinda Rana, Ph.D., from the University of California, San Diego, led one of the teams of investigators involved in a unique study to answer these questions. The study is examining the effects of a year's spaceflight on NASA astronaut Scott Kelly in comparison to his identical twin and fellow astronaut, Mark Kelly, who remained on Earth. Results of the NASA Twins Study are being published in the prestigious journal Science on April 12. The study is an integrated multiomics, molecular, physiological and behavioral analysis of the changes that occurred during a yearlong spaceflight.
Changes likely within range for humans under stress "Given that the majority of the biological and human health variables remained stable, or returned to baseline, these data suggest that human health can be mostly sustained over this duration of spaceflight," a NASA release stated. About 7 percent of gene expression changes persisted after six months on Earth, NASA reported. Targeted countermeasures will need to be developed as space travel to Mars and beyond is anticipated to increase in the 2020s and 2030s, NASA said.
Metabolite alterations and link to mitochondria The Center for Renal Precision Medicine has previously identified several metabolites associated with mitochondria that are altered in diabetic kidney disease and contribute to mitochondrial dysfunction. "We were surprised to see there was a similar pattern of metabolite alterations in Scott Kelly, who went up into space," Dr. Sharma said. Analysis showed that a metabolite called lactate was increased in Scott Kelly during his spaceflight and reverted to normal levels when he returned back to earth. "That was very exciting for us because lactate is directly connected to mitochondrial function," Dr. Darshi said.
Conversion to an alternative, and perhaps not so desirable, fuel-generating process "Thus, elevated lactate could potentially mean your mitochondria are not functioning normally," Dr. Sharma said. "As part of this study, other groups have evaluated mitochondrial function and mitochondrial gene expression, and the data supported our findings." The researchers don't yet know the reason for the increase in lactate in Scott Kelly, because levels can change with increased exercise, low oxygen, stress and inflammation, Dr. Sharma said. Follow-up studies with mouse models that traveled to space will add more to this exciting story. The NASA Twins Study utilized the expertise of teams from top universities in multiple disciplines, including genomics, proteomics and metabolomics. "We were the targeted metabolomics site and also coordinated the proteomics study with our collaborator," Dr. Sharma said.
Spaceflight connected to oxygen deprivation stress, increased inflammation and nutrient shifts "This is exactly what precision medicine is about," Dr. Sharma said. "At an individual level, what can we measure and learn in a specific context? In this case, it happened to be a spaceflight. But it could be somebody taking medication for diabetes or starting an exercise regimen or beginning a new dietary plan." Customizing the individual's prescription based on their "omics" is the desired goal, he said.
The logistics of obtaining samples Institutions from coast to coast were involved in the overall study. "It's a great way to do team science," Dr. Sharma said. "This is the way team science will be able to address both simple and complicated questions, and could arrive at comprehensive answers a lot faster than individual teams have been able to do in the past."
Will cyborgs be made from melanin? Pigment breakthrough enables biocompatible electronics Washington DC (SPX) Mar 27, 2019 The dark brown melanin pigment, eumelanin, colors hair and eyes, and protects our skin from sun damage. It has also long been known to conduct electricity, but too little for any useful application - until now. In a landmark study published in Frontiers in Chemistry, Italian researchers subtly modified the structure of eumelanin by heating it in a vacuum. "Our process produced a billion-fold increase in the electrical conductivity of eumelanin," say study senior authors Dr. Alessandro Pezzel ... read more
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