Spoilers for Book 3 of the Mistborn series.
When Preservation's body falls from the mists, do we know what actually killed him? Was it the equivalent of old age or he just ran out of energy? Ruin couldn't hurt him directly right?
First of all, it's important to note that Preservation didn't die. It can't die, it's not alive. The Shards are some as-yet-unknown, but immensely powerful, kind of magic that, as far as we know, can't be destroyed completely. (They can be shattered, though, which has happened to other shards, but that's different from what happened to Preservation.)
However, the person holding the shard, at any give time, can die. The Shards make them very powerful and ageless, but not immortal, as Mistborn clearly indicates.
The body that falls from the mists is that of Leras, the original shard holder of Preservation. Ultimately, Leras/Preservation wanted to stop Ati/Ruin, but he had been holding the Shard for so long that he was simply unable to take an action that would destroy or undo anything. Instead, he began pouring more and more of Preservation's power into making the mists; the power of Allomancy came from Preservation, so the more people burning metals, the faster Preservations power was being used up. Note that the power wasn't going away, but it was being dispersed into the world, causing Leras to grow weaker.
At the same time, Ruin was fighting to destroy Preservation, again because that's what Ruin does -- it destroys things. This is why Ruin was so desperate to find the atium cache, to restore the missing parts of its power so it would be stronger than Preservation.
Ultimately, Leras' plan was to allow himself to run out of energy, between using it to create more Mistings and using it to fight Ruin. Once this happened, without the power of Preservation to keep him alive, his body would die off.
This released Preservation back into the world where Kelsier, then Vin, and then finally Sazed were able to take it up and use it.
I guess a question entirely in spoiler gets an answer entirely in spoiler.
Ruin killed Preservation (or if you like, Ati killed Leras). Preservation was definitely weak after ages of channeling the binding of Ruin, but even weakened gods in this universe don't seem likely to die on their own. The only thing preventing Ruin from killing Preservation in older times was the balance of their powers. Preservation sacrificed that balance slightly at first to create sentient humanity, and then solidly sacrificed again when he fully thrust most of his power into Ruin's binding. Once that was undone at the Well, we are left with a medium-and-revving-up-to-full-strength Ruin and a minimal-strength Preservation, who had no time to regain power or gather himself back together. Ruin probably toyed with him a bit, or let him waste what strength remained trying to hold together the world (the mists did keep the sun from char-broiling the surface for a time). In the end, Ruin could assault Preservation with a fraction of his power, and if Preservation was wasting the last of his energy, say, trying to communicate with Elend, rather than defend himself, well that would just bring the end a little quicker.