Department of Neurology, Jena University Hospital, 07747 Jena, Germany.
Jena Center for Healthy Aging, Jena University Hospital, 07747 Jena, Germany.
Cells. 2023 Aug 17;12(16):2086. doi: 10.3390/cells12162086.
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.
自约瑟夫·奥特曼（Joseph Altman）发表了他关于成年大鼠海马体神经发生的开创性工作以来，该领域的出版物数量呈指数级增长。如今，我们知道成年海马体中存在着一群成年神经干细胞（NSC），它们是终身神经发生和可塑性的来源。这些 NSCs 的功能受到来自邻近细胞和全身环境的外在线索的调节。然而，这种紧密的调节受到年龄失衡的影响，导致成年 NSCs 和神经发生减少，这导致了与海马体相关的认知功能的逐渐恶化。尽管进行了广泛的研究，但神经发生随年龄下降的机制仍不完全清楚，但似乎包括 NSC 静止增加、分化模式变化和 NSC 衰竭。在这篇综述中，我们总结了最近改善我们对海马体 NSC 衰老认识的工作，重点介绍 NSC 内在机制以及龛位和全身环境中的细胞和分子变化，这些变化可能与 NSC 功能随年龄下降有关。此外，我们确定了未来可能有助于我们理解 NSC 衰老和随之而来的海马体神经发生和可塑性丧失的方向。
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