OBJECTIVES:
While it is well established that telomere length erodes with normal aging, it is becoming increasingly appreciated that telomere length is also influenced by a variety of other factors including life stress, infection, and inflammation. Inflammation also results in oxidative stress, both being known contributors to telomere erosion. Recent research supports telomere maintenance as a key integrating component for the cumulative effects of genetic, environmental, and lifestyle factors on aging and aging-related diseases. The rate of telomere length change, therefore, provides an informative biomarker of biological aging. Further, dysfunction/decline of telomere length can be linked to age-related pathologies, ranging from reduced immune function and loss of fertility, to cardiovascular disease and cancer.
Preservation of telomere length requires telomerase, the specialized reverse transcriptase capable of de novo addition of telomeric repeats onto the very ends of newly synthesized telomeres. Telomerase activity is prominent in highly proliferative cells like stem, germline, and cancer, but virtually absent in normal somatic cells. Changes in diet and lifestyle have been shown to modulate telomerase activity, with healthy lifestyles and diets being positively correlated with telomere length. It has been demonstrated that ionizing radiation also influences telomeres and telomerase. However, the relationships between telomere length and telomerase activity (measured in blood lymphocytes), lifestyle factors, and environmental exposures are largely unknown. The investigators speculate that for the astronauts, telomere maintenance represents a particularly relevant biomarker, as it reflects the combined exposures and experiences encountered during space travel. That is, an individual astronaut’s genetic susceptibilities, exposures to galactic space radiations, nutritional, physical, and psychological stressors encountered, are all captured as changes of telomere length maintenance; telomeres don't forget.
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APPROACH:
The overall goal of this study was to identify and begin to define the risk of accelerated telomere shortening and changes in telomerase activity associated with space flight, a lifestyle with a variety of unique stressors and exposures. Recruitment of astronauts and healthy age, gender-matched ground control subjects was successfully accomplished, and crewmembers' telomere length and telomerase activity was monitored. Samples were collected preflight, inflight, and postflight to evaluate long-term/permanent changes.
RESULTS:
Astronauts in general tended to have shorter telomeres at baseline than healthy age/gender matched ground control subjects. They also tended to have lower levels of telomerase activity than ground control subjects. Unfortunately, telomerase activity was “lost in space” for all of inflight samples, likely due to unavoidable transit time and/or conditions (e.g., temperature) during return via Soyuz from the International Space Station (ISS) and then to Johnson Space Center (JSC). Most striking was the observation of significantly longer telomeres of crewmembers who spent six months on the ISS. Astronauts in general tended to have shorter telomeres after flight than they did before. Upon return to Earth, average telomere length shortened rapidly (by the R+7 timepoint).
Cell by cell analyses by Telo-FISH and generation of individual telomere length distributions revealed dramatic shifts in the shortest and longest telomere populations, consistent with the observed changes in average telomere length. Results further supported chromosomal inversions as informative biomarkers or “signatures” of space radiation exposure, and were suggestive of persistent genome instability post flight; i.e., frequencies remained elevated. Evidence of telomere replication stress and recombination were also observed during space flight.
Crew health and performance is critical to successful human exploration beyond low Earth orbit.
The Human Research Program (HRP) investigates and mitigates the highest risks to human health
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Risks include physiological and performance effects from hazards such as radiation, altered gravity,
and hostile environments, as well as unique challenges in medical support, human factors,
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