This obviously depends on your niche as some niches mailing list will be more susceptible to regular emails then others. If you aren't sending out emails too much but people are still unsubscribing then perhaps you are always sending "selling" emails. Does every email you send out just happen to have a product being suggested in there?
Well regular people will know your game from early on and whilst people like buying they hate being sold too. So checking their email inbox everyday and hearing mailing list about new offers will really annoy them and hence they will unsubscribe. I can guarantee that if people are unsubscribing on a regular basis it's because you are either emailing or trying to sell too much.
Cut it down and be more friendly to your list and they will stay with you. People like to get emails that are of value so try giving out things for free every mailing list now and then. With the world getting smaller everyday due to the existence of the Internet and its accessibility to a lot of the people worldwide, it is so amazing seeing how a person can send information to the rest of the world.