Clearing senescent stem cells from the brain enhances neurogenesis and cognitive function
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Clearing senescent stem cells from the brain enhances neurogenesis and cognitive function.
Senescent cells, which are chronically suppressed due to chronic stress, are partly responsible for tissue decline during aging.
Studies have shown that senescent cells play a negative role in age-related neurodegenerative diseases.
However, the cellular mechanisms that lead to tissue exhaustion during aging remain incompletely understood.
Several studies point to stem cells as targets for aging and aging-related functional decline.
Adult mammals have stem cells in their brains that continuously generate new neurons that are essential for cognitive ability.
The production of new neurons in the hippocampus declines rapidly with age, a phenomenon associated with reduced stem cell activity. Therefore, age-related accumulation of senescent cells may deregulate neural stem cells, which can negatively affect brain function .
Recently, researchers from the Hospital for Sick Children in Toronto, Canada published a research paper entitled: Restoration of hippocampal neural precursor function by ablation of senescent cells in the aging stem cell niche in the journal Stem Cell Reports .
This study shows that senescent cells in the senescent stem cell microenvironment directly contribute to neurogenic decline in the brain’s hippocampus, and that depletion of these cells can partially restore hippocampal neurogenesis and function.
According to corresponding author David Kaplan , stem cells exist throughout life and are damaged by aging, environmental stress and the degradation of the mechanisms that allow them to function optimally.
To survive, many stem cells revert to a dormant, unresponsive and inactive state.
Our goal is to awaken these dormant cells and, in doing so, enable them to perform biological functions that promote learning, memory and brain repair.
In this study, the research team tested the negative impact of increased aging in the neural stem cell niche (Stem cell niche) on normal stem cell function and adult neurogenesis in middle-aged mouse brains.
Pharmacological ablation of senescent cells with the anti-aging agent ABT-263 , a small-molecule apoptosis-inducing Bcl-2 inhibitor developed by Abbott Laboratories , resulted in a rapid increase in normal stem cell proliferation and neurogenesis, as well Hippocampal stem cells that can activate senescent cells. This sudden burst of neurogenesis had long-term effects in middle-aged mice.
One month after treatment with ABT-263, adult hippocampal neurons increased and hippocampal-dependent spatial memory was enhanced. “To our surprise, just one injection of the drug was enough to mobilize normal stem cells in the hippocampus, and the newly awakened stem cells continued to function normally for the next 30 days,” Kaplan said.
These results support the idea that senescent cells (primarily senescent stem cells) exhibit an aging-dependent accumulation in the hippocampal stem cell microenvironment, resulting in an age-related decline in hippocampal-dependent cognitive abilities.
Large numbers of stem cells age, preventing them from producing new neurons, and senescent stem cells may adversely affect unaged nerves.
When destroying harmful cells (senescent stem cells) in the microenvironment of aging stem cells to improve the surrounding environment, it can mobilize and awaken dormant stem cells, further enhancing hippocampal neurogenesis and cognitive function.
While these findings implicate a role for stem cells in age-related decline, stem cells are clearly not the only important senescent cell matrix in the nervous system.
In mouse models, depletion of senescent microglia, astrocytes, and oligodendrocyte progenitors that accumulate in the aging brain ameliorated some of the adverse consequences of neurodegeneration and obesity.
But these studies focused on senescent microglia and glial cells under neuropathological conditions, not normal senescent cells.
Furthermore, with age, deterioration of the stem cell microenvironment or surrounding environment triggers a dormant state, but most current research on awakening dormant stem cells has focused on mobilizing the cells themselves.
The next question to address, says David Kaplan , is whether simply reducing the number of senescent stem cells improves normal stem cell function and cognition, or whether removing other types of senescent cells also matters.
While the study was about removing senescent stem cells, reducing the number of all harmful senescent cells in the brain may yield the best results.
Reference :
https://doi.org/10.1016/j.stemcr.2021.12.010
Clearing senescent stem cells from the brain enhances neurogenesis and cognitive function
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