In Michael Rose's talk (about his Methuselah flies and what they mean for longevity) at the recent Immortality Institute conference in Brussels, he talked about the three diet regimes that humans have lived under: Hunter Gatherer (2.5M years(?), more gatherer at first, later more hunter); Agricultural (10K years), and Industrial (100 years). He said that humans adapt to new environments in 30-60 generations. 10,000 years is ~500 generations, which should be plenty of time for deleterious genes to be flushed out if they occur much prior to the end of reproduction, (35 years for women, older for men? Maybe an average of 40?) We clearly haven't had time to adapt to the modern 'industrial' diet.
Rose's hypothesis raises a very interesting point about the relationship between evolutionary pressure and diet. As you move from the start of your reproductive period to the end, the evolutionary pressure against possession of a deleterious gene decreases, when averaged over a population. In fact, because humans aid in raising their children and grandchildren, the pressure to drop deleterious genes actually continues (at a much lower level) somewhat beyond the end of reproduction. The upshot of this is that as you get older, it becomes more important to switch to a Paleo diet. Evolution has provided most of us with very good early life adaptations to an agricultural diet, but some of these adaptations begin to fail us later in life, while our ancestral adaptations to a Paleo lifestyle, due to the much longer time we had to develop them, are still active in later life. Rose's prescription for attaining a 'natural' version of the 'biological immortality' of his Methuselah flies is to switch to Paleo after 40. (Earlier if not Eurasian.) You can certainly start Paleo sooner, but it's not as necessary.
If you're in your 20's, you can get away with most anything; certainly an agricultural diet for all but a few of us, and some of us can eat an industrial diet without apparent harm. As you slide through your 30's, you will see things unravelling, as you get fat and your metabolism goes to hell.