Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging

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, quiesce...

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Published in:Science (American Association for the Advancement of Science) Vol. 359; no. 6381; p. 1277
Main Authors: Leeman, Dena S, Hebestreit, Katja, Ruetz, Tyson, Webb, Ashley E, McKay, Andrew, Pollina, Elizabeth A, Dulken, Ben W, Zhao, Xiaoai, Yeo, Robin W, Ho, Theodore T, Mahmoudi, Salah, Devarajan, Keerthana, Passegué, Emmanuelle, Rando, Thomas A, Frydman, Judith, Brunet, Anne
Format: Journal Article
Language:English
Published: United States 16.03.2018
Subjects:
Aging - physiology
Animals
Cell Division
Cellular Senescence
Lysosomes - physiology
Mice
Mice, Inbred C57BL
Neural Stem Cells - physiology
ISSN:1095-9203, 1095-9203
Online Access:Get more information
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Summary: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.
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ISSN:1095-9203
1095-9203
DOI:10.1126/science.aag3048