Lysosomes keep neuronal stem cells young An important consequence of aging is loss of regenerative capacity in stem cells, particularly those of the nervous system. Leeman et al. isolated quiescent and activated stem cells from mice and compared their transcriptomes. The findings emphasize the role of large lysosomes in quiescent neuronal stem cells in which aggregated proteins accumulate. Treatments that stimulated lysosomal function allowed aged quiescent stem cells to clear protein aggregates and restored the cells' ability to be activated. Such restoration of stem cell function might alleviate compromised proteostasis in aging. Science, this issue p. 1277 Characterization of aging neuronal stem cells points to lysosomes as a key factor in maintaining stemness. In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.

中文翻译：

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溶酶体激活清除聚集体并增强衰老过程中静止的神经干细胞激活

溶酶体使神经元干细胞保持年轻 衰老的一个重要后果是干细胞，尤其是神经系统细胞的再生能力丧失。李曼等人。从小鼠中分离出静​​止和激活的干细胞并比较它们的转录组。研究结果强调了大溶酶体在聚集蛋白质积聚的静止神经元干细胞中的作用。刺激溶酶体功能的治疗允许老化的静止干细胞清除蛋白质聚集体并恢复细胞的激活能力。干细胞功能的这种恢复可能会减轻衰老过程中受损的蛋白质稳态。科学，这个问题 p。1277 老化神经元干细胞的特征表明溶酶体是维持干细胞的关键因素。在成年人的大脑中，神经干细胞 (NSC) 池包含具有不同作用的静止和激活的细胞群。转录组学分析显示，静止和激活的神经干细胞在其蛋白质稳态网络中表现出差异。激活的 NSC 具有活性蛋白酶体，而静止的 NSC 包含大溶酶体。来自年轻小鼠的静止神经干细胞积累了蛋白质聚集体，其中许多聚集体储存在大溶酶体中。静止神经干细胞中溶酶体活性的扰动影响蛋白质聚集体的积累和静止神经干细胞的激活能力。在衰老过程中，静止的神经干细胞显示出溶酶体缺陷、蛋白质聚集体的积累增加和激活能力降低。