Final answer:
Lower oxygen extraction by muscle is the major factor causing a decrease in VO2 max at moderate altitudes (~4000 meters).
Step-by-step explanation:
The major factor causing a decrease in VO2 max at moderate altitudes (~4000 meters) is lower oxygen extraction by muscle. As altitude increases, the partial pressure of oxygen decreases, resulting in less oxygen being available for muscles to extract. This lowers the maximum amount of oxygen that can be taken up and used by the body, leading to a decrease in VO2 max.