Methods, systems and computer program products are provided for managing protection domains (PDs) for files at a file-level or a page-level. PDs may be allocated for multiple purposes, e.g., to protect processes, files, buffers, etc. Files stored in nonvolatile memory (NVM) subject to direct access (DAX) may be protected by file-level or page-level PDs. PDs may comprise protection keys (PKEYs) with user-configurable read and write access control registers (PKRUs). NVM files may be protected from corruption (e.g. by stray writes) by leaving write access disabled except for temporary windows of time for valid writes. File PDs may be managed by a file manager while buffer PDs may be managed by a buffer pool manager. File associations between PDs, files and file address space may be maintained in a file object. Buffer associations between PDs, buffers and buffer address space may be maintained in a buffer descriptor.