When a Classic ELB or Target Group has no registered instances, the ELB will not be able to route traffic anywhere. This will result in all requests and connections being rejected by the ELB.
If you are manually registering instances, it is possible that the previously registered instances got terminated. In this case, either create new instances to replace the terminated ones, or delete the ELB if it no longer receives traffic.
If your instances automatically register themselves using the EC2 API, ensure that they have permissions to do so.
If you have AutoScaling Groups that are registered with the ELB or Target Group, check to see if there are any instances in the ASG. If the ASG terminated all of its instances, then the ELB will have nowhere to send traffic. If your ASG uses spot instances, then perhaps the request price was too low and the ASG could not launch instances.