Project description:Space radiations and microgravity both could cause DNA damage in cells, but the effects of microgravity on DNA damage response to space radiations are still controversial. A mRNA microarray and microRNA microarray in dauer larvae of Caenorhabditis elegans (C. elegans) that endured spaceflight environment and space radiations environment during 16.5-day Shenzhou-8 space mission were performed. The analyzation this study are further described in Gao, Y., Xu, D., Zhao, L., Zhang, M. and Sun, Y. (2015) Effects of microgravity on DNA damage response in Caenorhabditis elegans during Shenzhou-8 spaceflight. International journal of radiation biology, 91, 531-539.
Project description:Space radiations and microgravity both could cause DNA damage in cells, but the effects of microgravity on DNA damage response to space radiations are still controversial. A mRNA microarray and microRNA microarray in dauer larvae of Caenorhabditis elegans (C. elegans) that endured spaceflight environment and space radiations environment during 16.5-day Shenzhou-8 space mission were performed. The analyzation this study are further described in Gao, Y., Xu, D., Zhao, L., Zhang, M. and Sun, Y. (2015) Effects of microgravity on DNA damage response in Caenorhabditis elegans during Shenzhou-8 spaceflight. International journal of radiation biology, 91, 531-539.
Project description:Space radiations and microgravity both could cause DNA damage in cells, but the effects of microgravity on DNA damage response to space radiations are still controversial.A mRNA microarray and microRNA microarray in dauer larvae of Caenorhabditis elegans (C. elegans) that endured spaceflight environment and space radiations environment during 16.5-day Shenzhou-8 space mission was performed. The analyzation this study are further described in Gao, Y., Xu, D., Zhao, L., Zhang, M. and Sun, Y. (2015) Effects of microgravity on DNA damage response in Caenorhabditis elegans during Shenzhou-8 spaceflight. International journal of radiation biology, 91, 531-539.
Project description:Microgravity and space radiation (SR) are two highly influential factors affecting humans in space flight. Many health problems reported by astronauts derive from endothelial dysfunction and impaired homeostasis. Here we describe the adaptive response of human, capillary endothelial cells to space. Reference samples on ground and at 1g onboard allowed discrimination between the contribution of microgravity and SR within the combined response to space. Cell softening and reduced motility occurred in space, with loss of actin stress fibers and a greater distribution of microtubules and intermediate filaments in compensation. The frequency of primary cilia also increased. DNA repair mechanisms were indeed activated. Transcriptomics highlighted the opposing effect of microgravity from SR on specific molecular pathways: radiation, unlike microgravity, stimulated pathways for endothelial activation (hypoxia, inflammation), DNA repair and apoptosis, promoting an ageing-like phenotype; microgravity, unlike SR, activated pathways for metabolism and pro-proliferation phenotype. Thus, microgravity and SR should be considered separately to tailor effective countermeasures to protect astronauts’ health.
Project description:Natural killer (NK) cells are important effectors of the innate immune system. Unlike T cells, NK cells do not require antigen-priming, making them an important first-line of defense against malignant cells. Because of the potential for increased cancer risk as a result of astronaut exposure to space radiation, we performed studies to determine whether conditions of microgravity present during spaceflight affects the body’s natural defenses against leukemogenesis. Human NK cells were cultured for 48 hours under normal gravity and simulated microgravity (smG), and cytotoxicity against K-562 (CML) and MOLT-4 (T-ALL) cell lines was measured using standard methodology or under continuous conditions of smG. Even this brief exposure to smG markedly reduced NK cytotoxicity against both leukemic cells using standard assay procedures, and these deleterious effects were even more pronounced in continuous smG. RNA-seq performed on NK cells from two healthy donors provided insight into the mechanism(s) by which smG reduced cytotoxicity. Given our prior report that human HSC exposed to simulated space radiation gave rise to T-ALL in vivo, the reduced cytotoxicity against MOLT-4 is striking and raises the possibility thatmG may add to astronaut risk of leukemogenesis during prolonged missions beyond LEO.
Project description:In space, multiple unique environmental factors, particularly microgravity and space radiation, pose constant threat to the astronaut’s health. To gain insight into the role of miRNAs and lncRNAs in response to radiation and microgravity, we analyzed RNA expression profiles in human lymphoblastoid TK6 cells incubated for 24 h in static condition or in rotating condition to stimulate microgravity in space after 2 Gy γ-ray irradiation. Expression of 14 lncRNAs and 17 mRNAs was found to be significantly down-regulated in the simulated microgravity condition. In contrast, irradiation up-regulated the expression of 55 lncRNAs and 56 mRNAs, while only one lncRNA, but no mRNA, was down-regulated. Furthermore, 2 miRNAs, 70 lncRNAs, and 87 mRNAs showed significantly altered expression under simulated microgravity after irradiation, and these changes were independently induced by irradiation and simulated microgravity. Together, our results indicate that simulated microgravity and irradiation additively and independently alter the expression of RNAs and their target genes in human lymphoblastoid cells.
Project description:As Earth’s magnetic field and ozone continue to weaken, space radiation begins pose a significant threat to the health of not only space travelers, but the world’s population. Space radiation and its high-energy and high-charge ions create distinct clusters of DNA and concentrated macromolecular damage that results in the accumulation of senescent cells (SnCs) known to play a critical role in promoting multimorbidity. Here we demonstrate that human fibroblasts exposed to different forms of space radiation acquire senescence-associated phenotypes including morphological alterations and the accumulation of SA-ßgal+ cells more efficiently than ꝩ-irradiation. Bulk and single cell RNA (scRNAseq) sequencing analysis revealed that space irradiated human fibroblasts up-regulated senescent-like phenotypes to a greater extent than γ-irradiation and enriched pathways associated with chronic activation and adaptation of the integrated stress response and NADPH-coupled redox metabolism. Healthy cells treated with conditioned media from irradiated SnCs manifested pro-inflammatory transcriptional profiles dependent on both radiation and cell type. Finally, treatment with known senotherapeutics demonstrated radiation-specific effects in primary dermal fibroblasts. Our data demonstrate that space radiation differentially induces senescent phenotypes in human cells compared to γ-irradiation that may play a key role in the pathogenic effects of space travel.