UPDATE 12/17/2015 2:30PM Pacific: I heard from Josh, the CEO of Unroll.me. He says:

Senders are seeing a spike in unsubscribe requests because Unroll.Me has been improving the process it uses to unsubscribe our users from emails they have chosen to unsubscribe from. This isn’t a bug and everything is working as it should.
This spike they are seeing is temporary and should level out once our recent improvements have caught up on the unsubscribe requests.

Requests should be processed as real unsubscribes.
At least one person I talked to was concerned as he personally called multiple subscribers who said they had not unsubscribed from his newsletter. If you are concerned about losing real subscribers, you do have some options. The most obvious is to send a single email, within 10 days of receiving the unsubscription request, notifying them that you received a request to unsubscribe through a 3rd party. Inform them you will be honoring the unsubscription request, but if the user was unsubscribed by mistake, they could resubscribe by clicking on a unique link.
Original Post
A lot of folks are talking about an anomalous increase in unsubscribes over the last few days.
Some information that’s been gathered so far and shared with me.

1. Unsub rates have increased by a significant factor (going from a few hundred to tens of thousands at some ESPs).
2. Only some senders are effected.
3. The unsubscribes are all to mailto: links
4. SomeOne unroll.me user reports are reporting being unsubscribed from their some of their lists without them asking remembering asking to unsubscribe. for it.
5. Conversations with some subscribers confirm they didn’t actively unsubscribe.

I’m still collecting information from folks, but the current version looks like there is something going on with unroll.me that is causing significant spikes in some sender’s unsubscribe rates.
Feel free to contact me directly if you have any information you’d like to share. I’ll keep updating this post throughout the day as I get info from people.
UPDATE 1:30PM Pacific:
More information is coming in and some people who I trust are starting to say that there was a bug in unroll.me’s code that meant some unsubscribes weren’t processed in a timely fashion. They’ve fixed that bug. They are now running through and resending all requests that weren’t initially sent. I’ve got inquiries into unroll.me to see if they can confirm this.
Some folks are saying the requests are primarily for older campaigns. Other folks are telling me they’re seeing new campaigns included in the unsub requests.
Hopefully unroll.me will clarify what’s going on. It really seems like something broke and they’re sending incorrect unsubscribe requests. But I’m hesitant to recommend ignoring the unsubscribes because if there is any way they’re valid, then that’s a violation of CAN SPAM. Not that I think the FTC will go after anyone for this, and CAN SPAM says that the 10 days starts when the request is received. 

unroll.me • unsubscribes