The present invention relates, in part, to the use of stem cells, such as placental-derived stem cells (PDSC), to reduce the effects of aging by, for example, restoring the regenerative engine and extending the lifespan of aging subjects. Provided herein, for example, 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 (e.g., PDSC), wherein the ratio is maintained or increased over time as compared to the ratio of the number of stem cells to the number of differentiated cells in a tissue of a control subject over time. 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 (e.g., PDSC), wherein the number of stem cells in the tissue of the subject is maintained or increased over time as compared to the number of stem cells in the same tissue of a control subject. 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 (e.g., PDSC), wherein the amount is effective to alter the environmental niche of the aging stem cell such that the phenotype or proteome of the stem cell is altered as compared to the phenotype of the stem cell resident in the tissue of a control subject.
