Evidence map›Paper›PMID 35063124›Full record

ArticleStem cell reports2022

Restoration of hippocampal neural precursor function by ablation of senescent cells in the aging stem cell niche.

Michael P Fatt, Lina M Tran, Gisella Vetere, Mekayla A Storer, Jaclin V Simonetta, Freda D Miller, Paul W Frankland, David R Kaplan

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Stem cell reports, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.

0numbers the graph read from it
0cells of the map it votes in
39citing papers in PubMed
6.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

39 citing papers in PubMed, 56 citations in OpenAlex.

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  10. Unleashing endogenous regeneration by senolytics.Journal of translational medicine · 2025
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  15. Senescent brain cell types in Alzheimer's disease: Pathological mechanisms and therapeutic opportunities.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 2 institutions in 1 country.

Michael P FattProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada.
Lina M TranProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada.
Gisella VetereProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Mekayla A StorerProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada.
Jaclin V SimonettaProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada.
Freda D MillerProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Michael Smith Laboratories, University of British Columbia, Vancouver, BC V6T 1Z4, Canada; Department of Medical Genetics, University of British Columbia, Vancouver, BC V6T 1Z4, Canada. Electronic address: freda.miller@msl.ubc.ca.
Paul W FranklandProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Physiology, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Psychology, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: paul.frankland@sickkids.ca.
David R KaplanProgram in Neurosciences and Mental Health, Hospital for Sick Children, 18-9716 PGCRL, 686 Bay Street, Toronto, ON M5G 0A4, Canada; Institute of Medical Science, University of Toronto, Toronto, ON M5S 1A8, Canada; Department of Molecular Genetics, University of Toronto, Toronto, ON M5S 1A8, Canada. Electronic address: dkaplan@sickkids.ca.
University of Toronto · CAHospital for Sick Children · CA

Funding

CIHR FDN143227CIHR MOP142267
6 · The paper itself

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.

Indexed as

AgingAniline CompoundsAnimalsCell ProliferationCellular SenescenceDentate GyrusFemaleHippocampusMaleMiceMice, Inbred C57BLNeural Stem CellsNeurogenesisSpatial MemoryStem Cell NicheSulfonamidesAniline CompoundsnavitoclaxSulfonamidesABT-263aginghippcampusneural stem cellsneurogenesissenescencesenescence-associated secretory phenotypesenolyticspatial memory

Identifiers

PMID35063124
PMCPMC8828532
OpenAlexW4206802794

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.