Over long enough time scales, replication errors and base pair flips will accumulate, and it's likely these effects will become problematic way before the state

Over long enough time scales, replication errors and base pair flips will accumulate, and it's likely these effects will become problematic way before the stated in vitro half life of 521 years. However, since we're talking about technologically enhanced life anyway, this opens the door to employing correction mechanisms that will actively repair such defects in vivo. In the end though, risks keep accumulating, both external and internal to the body. Intelligent biological life without digital backups does not seem to be the right platform for surviving time spans in excess of, say, a few hundred years.