Restoration of hippocampal neural precursor function by ablation of senescent cells in the aging stem cell niche.
Stem Cell Reports
; 17(2): 259-275, 2022 02 08.
Article
em En
| MEDLINE
| ID: mdl-35063124
ABSTRACT
Senescent cells are responsible, in part, for tissue decline during aging. Here, we focused on CNS neural precursor cells (NPCs) to ask if this is because senescent cells in stem cell niches impair precursor-mediated tissue maintenance. We demonstrate an aging-dependent accumulation of senescent cells, largely senescent NPCs, within the hippocampal stem cell niche coincident with declining adult neurogenesis. Pharmacological ablation of senescent cells via acute systemic administration of the senolytic drug ABT-263 (Navitoclax) caused a rapid increase in NPC proliferation and neurogenesis. Genetic ablation of senescent cells similarly activated hippocampal NPCs. This acute burst of neurogenesis had long-term effects in middle-aged mice. One month post-ABT-263, adult-born hippocampal neuron numbers increased and hippocampus-dependent spatial memory was enhanced. These data support a model where senescent niche cells negatively influence neighboring non-senescent NPCs during aging, and ablation of these senescent cells partially restores neurogenesis and hippocampus-dependent cognition.
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Base de dados:
MEDLINE
Assunto principal:
Senescência Celular
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Nicho de Células-Tronco
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Células-Tronco Neurais
Idioma:
En
Ano de publicação:
2022
Tipo de documento:
Article