Alzheimer’s Amyloid-β Accelerates Cell Senescence and Suppresses SIRT1 in Human Neural Stem Cells DOI Creative Commons

Rongyao Li,

Yi Li,

Haowei Zuo

et al.

Biomolecules, Journal Year: 2024, Volume and Issue: 14(2), P. 189 - 189

Published: Feb. 4, 2024

As a lifelong source of neurons, neural stem cells (NSCs) serve multiple crucial functions in the brain. The senescence NSCs may be associated with onset and progression Alzheimer’s disease (AD). Our study reveals noteworthy finding, indicating that AD-associated pathogenic protein amyloid-β (Aβ) substantially enhances senescence-related characteristics human NSCs. These encompass enhanced expression p16 p21, upregulation genes senescence-associated secretory phenotype (SASP), increased SA-β-gal activity, activation DNA damage response. Further studies revealed Aβ treatment significantly downregulates SIRT1 which plays role regulating aging process decreases downstream PGC-1α FOXO3. Subsequently, we found overexpression alleviates range Aβ-induced senescent markers Taken together, our results uncover accelerates cellular NSCs, making highly promising therapeutic target for contribute to age-related neurodegenerative diseases, including AD.

Language: Английский

Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate DOI Creative Commons
Ram Prosad Chakrabarty, Navdeep S. Chandel

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(3), P. 394 - 408

Published: March 1, 2021

Language: Английский

Citations

284
Ageing and rejuvenation of tissue stem cells and their niches DOI
Anne Brunet, Margaret A. Goodell, Thomas A. Rando

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2022, Volume and Issue: 24(1), P. 45 - 62

Published: July 20, 2022

Language: Английский

Citations

218
Formation and integration of new neurons in the adult hippocampus DOI
Annina Denoth‐Lippuner, Sebastian Jessberger

Nature reviews. Neuroscience, Journal Year: 2021, Volume and Issue: 22(4), P. 223 - 236

Published: Feb. 25, 2021

Language: Английский

Citations

216
Adult Hippocampal Neurogenesis in Aging and Alzheimer's Disease DOI Creative Commons
Kelsey R. Babcock,

JOHN S. PAGE,

Justin R. Fallon

et al.

Stem Cell Reports, Journal Year: 2021, Volume and Issue: 16(4), P. 681 - 693

Published: Feb. 26, 2021

Cognitive deficits associated with Alzheimer's disease (AD) severely impact daily life for the millions of affected individuals. Progressive memory impairment in AD patients is degeneration hippocampus. The dentate gyrus hippocampus, a region critical learning and functions, site adult neurogenesis mammals. Recent evidence humans indicates that hippocampal likely persists throughout life, but declines age strikingly impaired AD. Our understanding how supports healthy adults only beginning to emerge. extent which decreased contributes cognitive decline aging remains poorly understood. However, studies rodent models other neurodegenerative diseases raise possibility targeting may ameliorate dysfunction Here, we review recent progress impacted context

Language: Английский

Citations

201
Neurogenesis in aging and age-related neurodegenerative diseases DOI Creative Commons

Luka Čulig,

Xixia Chu,

Vilhelm A. Bohr

et al.

Ageing Research Reviews, Journal Year: 2022, Volume and Issue: 78, P. 101636 - 101636

Published: April 29, 2022

Language: Английский

Citations

117
Early stem cell aging in the mature brain DOI Creative Commons
Albina Ibrayeva,

Maxwell Bay,

Elbert Pu

et al.

Cell stem cell, Journal Year: 2021, Volume and Issue: 28(5), P. 955 - 966.e7

Published: April 14, 2021

Language: Английский

Citations

106
Cell-type-specific aging clocks to quantify aging and rejuvenation in neurogenic regions of the brain DOI Creative Commons

Matthew T. Buckley,

Eric Sun, Benson M. George

et al.

Nature Aging, Journal Year: 2022, Volume and Issue: 3(1), P. 121 - 137

Published: Dec. 19, 2022

Abstract The diversity of cell types is a challenge for quantifying aging and its reversal. Here we develop ‘aging clocks’ based on single-cell transcriptomics to characterize cell-type-specific rejuvenation. We generated transcriptomes from the subventricular zone neurogenic region 28 mice, tiling ages young old. trained single-cell-based regression models predict chronological age biological (neural stem proliferation capacity). These clocks are generalizable independent cohorts other regions brains, species. To determine if these could quantify transcriptomic rejuvenation, datasets two interventions—heterochronic parabiosis exercise. Aging revealed that heterochronic exercise reverse in regions, but different ways. This study represents first development high-resolution data demonstrates their application

Language: Английский

Citations

98
Hyperactive neuronal autophagy depletes BDNF and impairs adult hippocampal neurogenesis in a corticosterone-induced mouse model of depression DOI Creative Commons
Kuo Zhang, Fan Wang,

Mengying Zhai

et al.

Theranostics, Journal Year: 2023, Volume and Issue: 13(3), P. 1059 - 1075

Published: Jan. 1, 2023

Background: Depression is a mental disorder that poses serious threat to human health.Adult hippocampal neurogenesis (AHN) closely associated with the efficacy of antidepressants.Chronic treatment corticosterone (CORT), well-validated pharmacological stressor, induces depressive-like behaviors and suppresses AHN in experimental animals.However, possible mechanisms chronic CORT action remain elusive.Methods: A (0.1 mg/mL, drinking water for 4 weeks) was applied prepare mouse model depression.Immunofluorescence performed analyze lineage, immunoblotting, immunofluorescence, electron microscopy, adeno-associated virus (AAV) expressing pH-sensitive tandemly tagged light chain 3 (LC3) protein were used neuronal autophagy.AAV-hSyn-miR30-shRNA knock down autophagy-related gene 5 (Atg5) expression neurons.Results: Chronic decreases brain-derived neurotrophic factor (BDNF) dentate gyrus (DG) hippocampus mice.Moreover, it markedly diminishes proliferation neural stem cells (NSCs), progenitor cells, neuroblasts impairs survival migration newborn immature mature neurons DG, which may be attributed changes cell cycle kinetics induction NSCs apoptosis.Furthermore, hyperactive autophagy possibly by increasing ATG5 causing excess lysosomal degradation BDNF neurons.Notably, inhibiting DG mice knocking Atg5 using RNA interference reverses decrease expression, rescues AHN, exerts antidepressant effects.Conclusion: Our findings reveal autophagy-dependent mechanism links reduced levels, suppression behavior mice.In addition, our results provide insights treating depression targeting hippocampus.

Language: Английский

Citations

91
Transcriptome dynamics of hippocampal neurogenesis in macaques across the lifespan and aged humans DOI Open Access
Wei Wang, Mengdi Wang, Meng Yang

et al.

Cell Research, Journal Year: 2022, Volume and Issue: 32(8), P. 729 - 743

Published: June 24, 2022

Language: Английский

Citations

89
Blood-to-brain communication in aging and rejuvenation DOI Open Access
Gregor Bieri, Adam B. Schroer, Saul Villeda

et al.

Nature Neuroscience, Journal Year: 2023, Volume and Issue: unknown

Published: Jan. 16, 2023

Language: Английский

Citations

87