You can reduce your memory consumption by doing the following:

• Your initial index can consume a lot of RAM.  Index your messages overnight by selecting from the Tools menu, Indexing > Index all Folders.
• If you are on IMAP, unsubscribe from folders that are infrequently used.
• Delete older messages that are no longer needed.
• Periodically compact some of your larger folders.
• If you are using Gmail:
• Limit the number of messages that appear in IMAP folders. This can be adjusted at Gmail on the Web / Settings / Forwarding and IMAP tab / Folder Size Limits.
• Consider unsubscribing from the All Mail folder, and use a different folder for Archiving.
• Unsubscribe from the Gmail "Important" folder if you are not actively using that label.
• Use Postbox Topics instead of Postbox Labels, as each time you use a Gmail Label it creates another copy of the message in Postbox.