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Science. 2018 Mar 16;359(6381):1277-1283. doi: 10.1126/science.aag3048. Epub 2018 Mar 15.

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

Author information

1
Department of Genetics, Stanford University, Stanford, CA 94305, USA.
2
Cancer Biology Program, Stanford University, Stanford, CA 94305, USA.
3
Biology Graduate Program, Stanford University, Stanford, CA 94305, USA.
4
Stanford Medical Scientist Training Program, Stanford University, Stanford, CA 94305, USA.
5
The Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, Department of Medicine, Division of Hematology and Oncology, University of California, San Francisco, San Francisco, CA 94143, USA.
6
Department of Neurology and Neurological Sciences, Stanford University School of Medicine, Stanford, CA 94305, USA.
7
Glenn Center for the Biology of Aging at Stanford University, Stanford, CA 94305, USA.
8
Department of Biology, Stanford University, Stanford, CA 94305, USA.
9
Department of Genetics, Stanford University, Stanford, CA 94305, USA. anne.brunet@stanford.edu.

Abstract

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.

PMID:
29590078
PMCID:
PMC5915358
DOI:
10.1126/science.aag3048
[Indexed for MEDLINE]
Free PMC Article

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