Disclosed herein are polynucleotide agents (including interfering RNA agents (RNAi)), small molecule agents, and synthetic cells, methods of making the same, and their use as therapeutics against age-related dysfunction and/or cellular dysfunction that results in various disease states. In some embodiments, one or more agents as disclosed herein can be used to target and/or decrease the expression of the paired-box protein 5 (PAX5) gene, protein phosphatase, Mg2+/Mn2+ dependent 1F (PPM1F) gene, or both. Also disclosed herein are methods for the preparation and use of synthetic cells prepared by in vitro and/or in vivo manipulation using one or more cellular factors, polynucleotide agents, and/or small molecule agents. Disclosed herein is the use of these cells as therapeutic cells that treat age-related dysfunction and/or cellular dysfunction resulting in various disease states.