##Adapting humans to an oxygen-free environment through gene regulation: the challenges of Space travel In order to adapt to the harsh environment of space travel, especially long-term exposure to anaerobic or low-oxygen environments, scientists are exploring gene regulation to enhance human tolerance to hypoxia. The following are some potential research directions： **1. Enhance cell tolerance to hypoxia:** *** Regulation of the HIF-1 pathway: ** Hypoxia inducing factor-1 (HIF-1) is a key regulatory factor for cells to perceive and adapt to the hypoxic environment. Enhancing the activity of HIF-1 through gene editing technology can promote the survival of cells under hypoxic conditions, such as increasing blood vessel production, promoting red blood cell production, and regulating cell metabolism. *** Activate the antioxidant defense system: ** Hypoxia can lead to the accumulation of reactive oxygen species (ROS), which can cause damage to cells. Enhancing the cell's antioxidant defense system through gene regulation, such as superoxide dismutase (SOD) and glutathione peroxidase (GPx), can reduce the toxic effects of ROS and improve the survival rate of cells in anoxic environments. **2. Change metabolic pathways to adapt to an anaerobic environment:** *** Enhance anaerobic glycolysis: ** Under hypoxic conditions, cells mainly rely on anaerobic glycolysis to produce energy. Enhancing the activity of oxygen-free glycolysis-related enzymes through gene regulation, such as hexokinase (HK) and lactate dehydrogenase (LDH), can increase the energy supply of cells in an oxygen-free environment. ***Introduction of alternative energy metabolism pathways: ** Some organisms can use other substances as an energy source under anaerobic conditions, such as sulfate-reducing bacteria, which can use sulfate for anaerobic respiration. Introducing related metabolic pathways into human cells through genetic engineering may provide humans with a new source of energy in an oxygen-free environment. **3. Development of artificial oxygen carrier:** *** Design an oxygen carrier based on hemoglobin: ** Hemoglobin is the protein responsible for transporting oxygen in red blood cells. Through genetic engineering to modify the structure of hemoglobin, its binding ability to oxygen can be improved, or artificial oxygen carriers that can store and release oxygen under anaerobic conditions can be developed. ***The use of microorganisms to synthesize oxygen: **Some cyanobacteria and photosynthetic bacteria can produce oxygen through photosynthesis. Genetic engineering to modify these microorganisms so that they can survive in the space environment and efficiently produce oxygen may provide a sustainable source of oxygen for mankind. **Challenges and ethical considerations:** *** Safety of gene editing technology: ** At present, gene editing technology is still in the development stage, and its long-term safety and potential risks still need to be further evaluated. *** Ethical issues: **Gene editing of human embryos to enhance their tolerance to hypoxia involves a series of ethical issues, such as the fairness of gene enhancement and the potential impact on the human gene pool. ***Individual differences: **There are differences in the tolerance of different individuals to hypoxia, and gene regulation programs need to be individually designed according to individual circumstances. **Conclusion:** Enhancing human tolerance to hypoxia through gene regulation is a potential way to solve the oxygen supply problem in space travel. However, research in this field is still in its early stages and faces technical, ethical and other challenges. In the future, scientists, ethicists and all walks of life will be required to work together to promote research and development in this field while ensuring safety and ethics, and to provide support for mankind to explore a broader space in the universe.