Although the phenotype of T-cell senescence has been extensively investigated, few studies have analyzed the factors that promote the generation and maintenance of naïve and memory T cells that exist throughout the lifespan of the individuals. Unlike senescent T cells, naïve and memory T cells are able to participate in useful immune responses as well as respond to new activation. Hormones such as leptin, ghrelin, insulin-like growth factor 1, IGFBP3, and cytokines, including IL-7, regulate both thymopoiesis and maintenance of naïve T cells in the periphery. Although chronic viruses such as cytomegalovirus (CMV) are thought to drive T-cell senescence, other microbes may be important for the maintenance of nonsenescent T cells. Microbiota of the gut can induce metabolic syndrome as well as modulate T-cell development into specific subpopulations of effector cells. Finally, T-cell generation, maintenance, and apoptosis depend upon pathways of energy utilization within the T cells, which parallel those that regulate overall metabolism. Therefore, better understanding of metabolic syndrome, T-cell metabolism, hormones, and microbiota may lead to new insights into the maintenance of proper immune responses in old age. © 2010.