New neurons in an aged brain

Adult hippocampal neurogenesis is one of the most robust forms of synaptic plasticity in the nervous system and occurs throughout life. However, the rate of neurogenesis declines dramatically with age. Older animals have significantly less neural progenitor cell proliferation, neuronal differentiation, and newborn neuron survival compared to younger animals. Intrinsic properties of neural progenitor cells, such as gene transcription and telomerase activity, change with age, which may contribute to the observed decline in neurogenesis. In addition, age-related changes in the local cells of the neurogenic niche may no longer provide neural progenitor cells with the cell–cell contact and soluble cues necessary for hippocampal neurogenesis. Astrocytes, microglia, and endothelial cells undergo changes in morphology and signaling properties with age, altering the foundation of the neurogenic niche. While most studies indicate a correlation between decreased hippocampal neurogenesis and impaired performance in hippocampus-dependent cognitive tasks in aged mice, a few have demonstrated that young and aged mice are equivalent in their cognitive ability. Here, we summarize the different behavioral paradigms to test hippocampus-dependent cognition and the need to develop neurogenesis-dependent tasks.

► Adult hippocampal neurogenesis and cognitive function decline with age.
► Regulation of neurogenesis altered at both intrinsic and extrinsic levels with age.
► Newborn neurons can develop into fully functional neurons in an aged brain.