Yes, that can be hard. To make it easier, here are effective ways to communicate a "no."
* Pause. Count to three before saying anything. Wait until the other person rushes to fill the void with "Oh, never mind."
* Say "OK, but what should I deprioritize?" That last is a work word, of course. Outside the office, put it as "Hmm, I can if I quit my exercise Class and the Sunday School class I teach every week."
* Try "I can't, but so-and-so might help." Even with tasks as odious to you as cleaning out a garage, some people don't mind or even enjoy them.
* Soften the "no" with what you are willing to do. For instance, "No, I can't mentor your nephew, but I can give him some advice in a quick phone call."