HDD constantly running, slowing down PC

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Win 10 pro, Dell Optiplex, 8gb ram, three HDDs, boot drive and storage drive are conventional, third drive is SSD. I run three browsers for different uses, and have several email accounts running on Thunderbird, Office and several third party apps. My saved email folders are enormous.
Startup is optimised by Winpatrol, I run Glary registry cleaner and wipe cache once a week.
Boot takes five minutes at best, four if left on Sleep overnight, and the discs thrash away for about thirty minutes before settling down, but occasionally start chundering away and really slowing down the system.
I have tried many suggestions, too many to recall individually. Compressing and indexing are turned off on all drives. A clean install is not an option.
Where should I start looking for a resolution to this frustrating problem please?
 
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Replacing the boot drive with an SSD is the best solution. I've found boot times get longer and longer on mechanical drives, to where a clean install is really the only fix.
 
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Replacing the boot drive with an SSD is the best solution. I've found boot times get longer and longer on mechanical drives, to where a clean install is really the only fix.
+1
HDDs suffer from Seek and Latency times in addition to the data transfer time, SSDs do not. On fragmented HDD drives, and especially on large (1TB or more) fragmented drives, the seek times can be very large.

The Windows system should be on the fastest drive you can afford. If your board supports M.2 drives then a fast NVMe SSD drive is the best choice for a system drive. Your existing SSD can serve for high performance user data and the HDDs are perfect for music and videos (which get no benefit from being on an SSD at all).

BTW. I would advise against using the registry cleaner. The Windows registry doesn't need cleaning, if it did then Windows would contain a tool to do it.
 
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Try defragmenting your hard disks.
then make sure your primary boot drive is connected to the primary port on the motherboard. (it should be outlined in a certain color like red or yellow)
 
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And last thing would be: dump optimizers and download dell support assist as it has its own optimizer and it works awesome not only can it clear cache it optimizes system performance, internet connection scans your hardware for errors (including your harddrive) and downloads drivers. Before you try spending money or buying SSDs (which buying an SSD is an awesome idea) swap your SSD as your primary boot drive, or install dell support assist. Try dell support assist.
 
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OP here, thank you for your suggestions. I will attempt to clone the system drive to my SSD and see what happens. What really bothers me is the amount of time my HDDs are thrashing away - what are they doing? As I write this they are churning like mad for no apparent reason - I have looked at the activity monitor and there is nothing obviously strange - and the PC has been on all day so it is not boot-related. Whatever is going on I fear will continue on the SSD, but silently so I will not be aware of it. Just to clarify, my boot disk is a 1tb Seagate, there is a 1tb WD where I back stuff up, a 160gb WD with old files, and a 512 Kingston SDD with my current files.
 
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OP here, thank you for your suggestions. I will attempt to clone the system drive to my SSD and see what happens. What really bothers me is the amount of time my HDDs are thrashing away - what are they doing? As I write this they are churning like mad for no apparent reason - I have looked at the activity monitor and there is nothing obviously strange - and the PC has been on all day so it is not boot-related. Whatever is going on I fear will continue on the SSD, but silently so I will not be aware of it. Just to clarify, my boot disk is a 1tb Seagate, there is a 1tb WD where I back stuff up, a 160gb WD with old files, and a 512 Kingston SDD with my current files.
The HDD thrashing sounds like file fragmentation to me. If the drive is more than about 70% full then fragmentation really has an impact (because the seek times lengthen).

I would clean all the garbage from that disk with Windows Disk Cleanup tool. Then archive off anything you need to keep but don't use that often. Then, follow the advice of @windows user above and defrag the drive.
 
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An update. I decided to make my SSD the system disk and clone the spinning drive to it. Three days of struggling with AOEMI, Easus, Acronis, Macrium and Minitool, all totally failed or let me get to the final stage before coming up with a pay now demand. (Note, free download does not mean free use). Finally tried the little known but amazing Farstone Driveclone Free. Dead easy to use, really free, and did the job first try with no problems, automatically re-assigned the SSD as the C drive, and re-started the computer from the SSD. The whole system works far quicker, and no thrashing disks. Thanks to all who offered advice.
 
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