Age-associated degeneration of serotonin axons is well documented and may contribute to the increased incidence of late life neuropsychiatric and neurodegenerative disorders, as well as to a general decline in cognitive function. Previously, we demonstrated that constitutive reductions in serotonin transporter (SERT) expression in mice are associated with a reversal or prevention of normal age-related degeneration of serotonergic axons and we hypothesized that these changes may have a beneficial effect on anxiety-related behavior and/or learning and memory. In the present study, we assessed anxiety-related behavior in 18 month-old male and female SERT deficient mice using the elevated plus maze and the free choice exploration test. The latter is performed in the home cage to reduce stress associated with a novel environment. SERT-/- mice of both sexes showed significant increases in anxiety-like behavior in both paradigms as evidenced by (1) decreased numbers of entries into and time spent in the open arms of the plus maze and (2) decreased numbers of entries into the novel compartments in the free choice test. SERT-/- mice also showed decreased numbers of entries into the familiar compartments in the free choice test. This was not associated with a decrease in locomotor activity in the open field. No changes in anxiety-related behavior or locomotor activity were observed in SERT+/- mice of either sex. In addition to behavior, we assessed the survival and differentiation of new neurons in the subgranular zone of the hippocampus in 18 month-old SERT deficient mice. Mice were sacrificed 28 days after injection of BrdU and new neurons were identified by fluorescent double labeling of BrdU and NeuN. SERT-/- mice showed a 15% reduction in newly differentiated neurons compared to SERT+/+ and SERT+/- mice. These data suggest that the anxiety-related phenotype of mice lacking SERT is stable throughout life and that while life long reductions in SERT and associated increases in extracellular serotonin may protect serotonergic axons from age-related degeneration, these changes are not associated with increased hippocampal neurogenesis in old age.