Professional Mail Marketing
A good place to start would be with a professional email marketing company, such as MailChimp (there are many more)
Collate all your email addresses and get them into your desired software and start with a re-confirmation of that list - if you do not confirm that the people on the list want to be part of your mailer then you will run into problems; marked for spam, high rates of bouncing and unsubscribes.
You can add a page to your website where they can go and join your list - this would be my preferred action, one by one invite your email addresses to join your newsletter/mailshot list.
Many stale email addresses are flags when using any software, basically they know if your list hasn't been confirmed and is made of stale addresses, apart from of that though, your reports will be a mess and not make much sense.
Some suggestions of software you can use
And that is just to mention a few!
Good luck, once you have confirmed your email addresses your life will become a lot easier and at least you know the people you are sending to actually want it - nothing beats a well targeted audience.
I build my lists into categories, especially if I am running newsletters for companies who sell products of various different brands, my newsletters would be offers for product A and this would only be sent to list A (in my email software programme) - product B could be a generic mailshot so that would go to main list (which contains everyone).