It may be the overall stress of life in the space station provokes an immune response. But recent studies have also shown that latent viruses can awaken in astronauts.

Or maybe it’s that the immune system, which never evolved for survival in space, simply gets confused.

“Is it good or bad? We just know it’s more,” Dr. Mason, a co-author of the new study, said of the immune activity. “To know for sure, we’d need more astronauts.”

Mr. Kelly’s return to Earth on March 1, 2016, proved to be one of the biggest moments — biologically speaking — of the whole mission. His body showed signs of intense stress, and his immune system was in high gear.

Michael Snyder, a geneticist at Stanford University and co-author of the research, cautioned that this response might not be typical. “Maybe he got a viral infection,” he speculated. “This is why you want to see it in more people.”

Despite that shock, Mr. Kelly’s body mostly returned to preflight condition. Some species of bacteria that thrived in his gut while he was in space, for example, became rare again on his landing.

The strange lengthening of Mr. Kelly’s telomeres disappeared after less than 48 hours on Earth. In fact, Dr. Bailey and her colleagues started finding many cells with telomeres that were shorter than before Mr. Kelly went to space.