Compensatory mechanism in the age-induced decline of adult hippocampal neurogenesis

Beccari , S. 1, 2 & Sierra , A. 1, 2, 3

1 Achucarro Basque Center for Neuroscience, Bizkaia Science and Technology Park, Zamudio, Spain
2 University of the Basque Country, Leioa, Spain
3 Ikerbasque Foundation, Bilbao, Spain

Adult neurogenesis, the process of generating functional new neurons, persists in the subgranular zone (SGZ) in the dentate gyrus of the hippocampus throughout life. During aging, the SGZ neurogenic capacity undergoes a progressive decline, which is attributed to a loss of the neural stem cell pool. However, whether the remaining steps in the neurogenic cascade, namely stem cell proliferative activity, neuronal survival, progenitor migration or neuronal differentiation are also altered during aging, potentially compensating the loss of neural stem cells. In this study, we compared the SGZ niche of 1, 2, 6 and 12 month-old age mice to assess all phases of neurogenesis. In concordance with previous reports, we observed a dramatical decline in proliferation with increasing age but no major alterations in the survival and differentiation rates. Our data suggest that the strong age-related neuronal loss is not counteracted by any compensatory mechanism, neither of stem cell proliferation, or newborn cell differentiation and survival. Therefore, the age-related decline in neurogenesis is largely explained by the loss of neural stem cells alone.