I have looked into this topic in depth.
First, let's disregard the studies done by Dr. James O'Keefe. He says 10-20mpw is optimal, based on studies with incorrect cox regression analysis applied, and based on sample sizes of literally 3-5 runners doing high mileage. His ted talk does not mention this, but his studies have been heavily criticized in the journals he published. He also had a study where he looked at coronary arterial plaque in lifelong marathon runners, and found that those who ran a lot of marathons had terrible arterial plaque. However there were also more ex-smokers in the marathon runner group than the control group... The study also didn't correct for diet, which is the #1 cause for poor arterial function. "You can't outrun a bad diet."
The largest studies available show increased lifespan for up to 90 minutes a day of "vigorous" exercise, which includes running. The graphs clearly show more exercise is always better, but there is a plateau after about 60 minutes a day of vigorous exercise. In other words, 90 min/day isn't much better for lifespan than 60 min/day, but 60 min/day is substantially better than 30 min/day.
So one might take a medical approach to running as medicine, and ask the question, "what is the minimum effective dose?" or, the optimum dose before negative side effects start to occur.
Running more than certain distances and certain intensities leads to negative health impacts, such as a temporary drop in immune system function, and a temporary drop in testosterone production. Note that this may not decrease lifespan, but is it optimal to have suppressed testosterone levels, given that testosterone is so important for sex drive, concentration, and feelings of wellbeing? I think not. Large volume intense work-outs (races of 15K or more, high volume VO2max workouts, long runs of ~2 hours) seem to have these effects. There are many studies that show reduced testosterone after 60 minutes of exercise - it seems to be true for many different sports.
A study of BC distance runners from the year 2000 showed that those who ran more than 40mpw had low testosterone, though it was in the normal range. But it was a small study - just a few dozen participants.
So I think the cut-off is somewhere between 40-60mpw, and runs beyond about 60 minutes have marginal improvements in health/lifespan.