It strikes me that in many ways, life was gradually getting harder in the Old World, especially in the cradles of civilization. We know that every now and then a new infectious disease was added to the mix: smallpox probably shows up in the classical world around 180 AD, bubonic plague in 641, syphilis in 1494, cholera around 1830, HIV in the 1970s. Those we know – but many other infectious diseases must have arrived at some time since the beginning of the Holocene – certainly those like measles whose critical community size was too large for it to have existed among hunter-gatherers. Ancient DNA & molecular phylogeny should elucidate this negative trend. Bet you a dollar that typhus didn’t exist in the old days.
What, if anything, countered this gradually increasing disease burden? I would say selection – medicine was useless until quite recently. But selection is slow. Now and then an infectious disease seem to have disappeared (English sweat) or become milder (scarlet fever) but that was a coincidental outcome of some kind of ecological change – people didn’t plan it.
In the same way, farming should have gotten harder in some ways: the burden of weeds, blights, and insects should have increased with time. There, though, selection acted faster than it did in humans: crops have high effective population size and short generations. Of course, so do weeds… I know that chickpea, one of the original founder crops of the Middle East, disappeared for about 3,000 years because of a fungus – until a version that grew in the (dryer) summer showed up. Rye and oats started out as weeds and developed such effective mimicry that they became crops…
Then there’s environmental degradation – deforestation, erosion, soil salinization, exhaustion of ores useful to available techniques. Worse in fairly dry areas, worse with irrigation as opposed to rain-fed agriculture.
Technical innovations pushed in the other direction – decent horse harnesses, three-field cultivation, water mills, Champa rice – but it could be a long time between innovations. In particular Classical civ seems to have been low on such innovations.