The problem with something like a disease, or radiation, etc is that the "disease" has no way of knowing when you turn 25. It's also highly suspicious that it doesn't seem to affect you at all growing up, but then suddenly you die on your exact birthday. It's ridiculous.
More realistically, this disease would kill you around your 25th birthday - with some very strong individuals living to be quite old (27 say), and some weaklings dying at 20. Then it becomes more realistic.
1) Nanobots that infiltrated the population from the wreck of a crashed alien drone (in their medieval views their people scavenged sky metal and suffered a curse). These nanobots infected the hosts, etc.
2) A curse on their ancestors cast by a God/powerful wizard. (oops, you covered that)
3) That's just their genetic make-up. When you really get down to it, you don't really have to explain it. None of the characters would know what "genetics" are anyway, so how could they "talk" about it and explain it to the reader?
4) The radiation of their star slowly saturates your body and kills you around the age of 25 - because that's just how the timing works out (this premise if kinda shaky for some very obvious reasons, but hey, it's your imaginary universe)
5) On their world all people are infected with a parasite that is ubiquitous - simply can't be avoided - everyone is infected in the womb, or shortly thereafter. When that parasite "matures", or it itself dies, it's death/departure kills the host.
This parasite/human relationship is symbiotic, and the human receives some benefit from it. When the parasite leaves the host, its death is somehow beneficial to the world as a whole, and thus people see their short lives as being lived in sacrifice to their world.
Freaky as hell, and a pretty good explanation as such things go.
I can adjust some scenarios and flesh them out on request.
I'm going to roll with the parasite, and make this stuff right up:
a) The world was a perfectly normal place, as this universe goes. Then one day, an alien craft/asteroid crashes on the planet. This craft contains a parasitic life-form which attaches itself to its host, and spreads aggressively: perhaps it releases spores into the water/air which infect the host and cause that malignant life-form to grow inside its victim. There is simply no way to remove it without killing the host. Being of alien origin, this life-form has a life-span of its own: exactly 25 years. The victim dies not on their own 25th birthday, but on the 25th "birthday" of their parasite, which may have infected them a few days after birth, for example.
b) The world was a perfectly normal place, until one day an alien craft/asteroid crashes on the planet. This craft contains an alien life-form which is highly intelligent, but parasitic in nature, and which cannot survive for long on this world because of certain factors (radiation from the Sun, etc.).
This life-form uses psychic powers to communicate with the human elders. They propose a trade, to be accepted by the elders on behalf of all their descendants, or until a "rescue craft" arrives to take the aliens away (which might take many centuries to get here, but the aliens are crafty, and don't say this outright):
To allow their species to symbiotically attach to human hosts, in return for great power to those who "link" with them. However, there was a catch in the deal that the elders, foolishly thinking they could trick the aliens, accepted. When the host reaches the age of 25 - physical maturity, and thus greatest vitality - the alien claims its prize for having enhanced the human for all that time: it completely drains them of vitality, killing them, but extending the life of the alien, which is then passed to another host.
There can be great benefit to the alien attaching itself to a human: they might reach maturity faster, develop greater strength and intellect, as well as being immune to diseases, healing injuries faster, etc.
Any who try to detach the alien, are killed by the alien host. Any who try to fight the aliens are subdued via psychic powers. After all, a deal is a deal.
Over time, it can work out that a great plague wiped out all the humans that were not symbiotically attached to an alien, however the "survivors" are doomed as well, because their means of surviving the disease kills them upon reaching their 25th birthday.
-- is there any interest in me expanding on this idea, or am I beating a dead horse?