JM,
the C130 and the 747 are similar in technology and flight deck layout, and both fly with a flight engineer, so there are a lot of similarities in the basic operation. The C130 is much smaller and more manoeuvrable, and those big props give instantaneous speed control, so it's much nicer to fly in the pattern. The 747, like most jets, doesn't want to slow down, which can be awkward, and its flight director controls are an ergonomic nightmare for the non-flying pilot. On the C130, the handling pilot could operate all his own FD selections which is not recommended in the 747, so the workload on the approach is higher overall. A go-round is a major event as a result, and a relative non-event in the C130.
As for the physiological effects of long-haul flying, I'm not so sure. Most of the older pilots I fly with are pretty young-looking for their age, which may well be a benefit of a relatively low-stress lifestyle (which I find it is - but then, I'm single again!), and the deleterious effects of time-zone changes are relatively minor. Others would, no doubt, disagree!
There are, however, serious effects on your home life when you are as much use as a chocolate fireguard for 24 hours or more after your return from a trip. You may well only have 48 or 72 hours between trips, which means that it's very difficult to fit in all those things you (and your other half) currently take for granted. You need to be pretty organised, and have an understanding and independent other half, for it all to work smoothly.