From Youthful Vigor to Aging Decline: Unravelling the Intrinsic and Extrinsic Determinants of Hippocampal Neural Stem Cell Aging

Since Joseph Altman published his pioneering work demonstrating neurogenesis in the hippocampus of adult rats, the number of publications in this field increased exponentially. Today, we know that the adult hippocampus harbors a pool of adult neural stem cells (NSCs) that are the source of life-long neurogenesis and plasticity. The functions of these NSCs are regulated by extrinsic cues arising from neighboring cells and the systemic environment. However, this tight regulation is subject to imbalance with age, resulting in a decline in adult NSCs and neurogenesis, which contributes to the progressive deterioration of hippocampus-related cognitive functions. Despite extensive investigation, the mechanisms underlying this age-related decline in neurogenesis are only incompletely understood, but appear to include an increase in NSC quiescence, changes in differentiation patterns, and NSC exhaustion. In this review, we summarize recent work that has improved our knowledge of hippocampal NSC aging, focusing on NSC-intrinsic mechanisms as well as cellular and molecular changes in the niche and systemic environment that might be involved in the age-related decline in NSC functions. Additionally, we identify future directions that may advance our understanding of NSC aging and the concomitant loss of hippocampal neurogenesis and plasticity.

Automated summary

Since Altman's pioneering work, the number of publications on neurogenesis in the adult hippocampus has increased exponentially. The adult hippocampus contains neural stem cells that contribute to long-term neurogenesis and plasticity. However, with age, there is a decline in neurogenesis due to changes in NSC behavior and the surrounding environment, leading to the deterioration of cognitive functions related to the hippocampus. This review summarizes recent research on the aging of hippocampal neural stem cells, focusing on intrinsic mechanisms, as well as cellular and molecular changes in the niche and systemic environment that may contribute to the age-related decline in NSC functions.