The present invention relates to the use of stem cells, such as placental-derived stem cells (PDSC), to reduce the effects of aging by, restoring the regenerative engine and extending the lifespan of aging subjects. Provided are methods for maintaining or increasing the ratio of the number of stem cells to the number of differentiated cells in a tissue of a subject over time, comprising administering to the subject an effective amount of a population of stem cells. Further provided are methods of maintaining or increasing the number of stem cells in a tissue of a subject over time, comprising administering to the subject an effective amount of a population of stem cells. Also provided herein are methods of altering the phenotype or proteome of an aging stem cell resident in a tissue of a subject, comprising administering to the subject an effective amount of a population of stem cells.
