Background: The landmark National Aeronautics and Space Administration Twins Study represented an integrated effort to launch human space life science research into the modern age of molecular- and "omics"-based studies. As part of the first One-Year Mission aboard the International Space Station, identical twin astronauts Scott and Mark Kelly were the subjects of this "out of this world" research opportunity. Telomeres, the natural ends of chromosomes that shorten with cell division and a host of lifestyle factors and stresses, are key molecular determinants of aging and aging trajectories. Methods: We proposed that telomere length dynamics (changes over time) represent a particularly relevant and integrative biomarker for astronauts, as they reflect the combined experiences and environmental exposures encountered during spaceflight. Telomere length (quantitative polymerase chain reaction and telomere fluorescence in situ hybridization) and telomerase activity (quantitative polymerase chain reaction -telomere repeat amplification protocol) were longitudinally assessed in the space- and earth-bound twins. Chromosome aberrations (directional genomic hybridization), signatures of radiation exposure, were also evaluated. Results: The twins had relatively similar telomere lengths before spaceflight, and the earth-bound twins' telomeres remained relatively stable over the course of the study. Surprisingly, the space twins' telomeres were longer during spaceflight, and upon return to Earth shortened rapidly, resulting in many more short telomeres after spaceflight than before. Chromosomal signatures of space radiation exposure were also elevated during spaceflight, and increased inversion frequencies persisted after spaceflight, suggestive of ongoing genome instability. Conclusion: Although the definitive mechanisms underlying such dramatic spaceflight-associated shifts in telomere length remain unclear, improved maintenance of telomere length has important implications for aging science and improving healthspan for those on Earth, as well.
