Before earning his Ph.D. in exercise physiology, Peter Snell was, of course, a three-time Olympic gold medalist who also set five world records. Here is his advice on long runs:
Two primary systems are responsible for the delivery of oxygen to the muscles and its utilization for energy production: first, the heart and circulation, which deliver oxygen to the muscles. The muscles constitute the second system whereby oxygen is extracted from the blood and enters the mitochondria where the major energy-producing pathways reside.
VO2 max is a measure of the capacity for oxygen delivery more correctly known as aerobic power and depends on cardiac performance. Aerobic capacity refers to the extent to which a runner can sustain their aerobic power and this is dependent on muscle adaptation, which seems to take years to fully develop compared to VO2 max.
After VO2 max is fully developed in the first six months of endurance training, continued runs of about 70 percent VO2 max for at least 90 minutes are effective for further muscle adaptations, including capillary growth. By the process of glycogen depletion, muscle fibers initially active drop out after the first hour (roughly) and others, including fast-twitch, are called into action. Normally these fast-twitch fibers would only be recruited during high-intensity interval training. (Two roads to Rome here.) It's axiomatic that for a fiber to adapt it must be stimulated to contract; how much, how often is up in the air, which is why training is still an art.
If the distance running is too slow, it's likely that the energy can be provided largely by fat metabolism, thus sparing muscle glycogen. This means that once conditioned, the runner needs to run at close to maximal steady state pace during these longer runs.
Finally, all running presents an adaptive stimulus to the heart, the circulation and the muscle fibers. It's a question of understanding when the law of diminishing returns kicks in for a particular system.