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Senescent cells, chronically inhibited by chronic stress, are partly responsible for tissue decline during aging
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Studies have shown that senescent cells play a negative role in age-related neurodegenerative diseases
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However, the cellular mechanisms that lead to tissue exhaustion during aging remain incompletely understood
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Several studies point to stem cells as targets for aging and aging-related functional decline
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Adult mammals have stem cells in their brains that continually generate new neurons that are critical to cognitive ability
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The production of new neurons in the hippocampus decreases rapidly with age, a phenomenon associated with decreased stem cell activity
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Therefore, age-related accumulation of senescent cells may deregulate neural stem cells, which can negatively affect brain function
Recently, researchers at the Children's Hospital of Toronto, Canada published a research paper titled "Recovery of hippocampal neural precursor function by ablation of senescent cells in the senescent stem cell niche" in the journal Stem Cell Reports
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This study shows that senescent cells in the senescent stem cell microenvironment directly lead to the decline of neurogenicity in the brain's hippocampus, and the loss of these cells can partially restore hippocampal neurogenicity and function
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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
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To survive, many stem cells revert to a dormant, unresponsive and inactive state
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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
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In this study, the team tested the negative effects of aging in the neural stem cell niche on normal stem cell function and adult neurogenesis in the brains of middle-aged mice
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The anti-aging agent ABT-263 developed by Abbott is a small molecule Bcl-2 inhibitor that induces apoptosis.
By treating senescent cells with drugs, normal stem cell proliferation and neurogenesis can be rapidly increased, and hippocampal stem cells of senescent cells can also be activated.
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This sudden burst of neurogenesis had long-term effects in middle-aged mice
After 1 month of ABT-263 treatment, the number of neurons in the adult hippocampus increased and hippocampal-dependent spatial memory was enhanced
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"To our surprise, just one injection of the drug was enough to mobilize normal stem cells in the hippocampus, and those awakened stem cells continued to function normally for the next 30 days," Kaplan said
These results support the idea that senescent cells (mainly senescent stem cells) exhibit an age-dependent accumulation in the hippocampal stem cell microenvironment, leading to 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 can adversely affect unaged nerves
When detrimental cells in the aging stem cell microenvironment (senescent stem cells) are destroyed to improve the surrounding environment, dormant stem cells can be mobilized and awakened to further enhance 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, reduced accumulation of aging microglia, astrocytes, and oligodendrocyte progenitor cells in the aging brain ameliorates 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
In addition, deterioration of the stem cell microenvironment or surrounding environment can trigger a dormant state with age, but most current research on awakening dormant stem cells has focused on mobilizing the cells themselves
The next question to address, Kaplan said, 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 this study was about removing senescent stem cells, reducing the number of all harmful senescent cells in the brain may have the best effect
Original text retrieved: https://doi.
