Senescence: A DNA damage response and its role in aging and Neurodegenerative Diseases
Tejal Shreeya1,2, Mohd Saifullah Ansari3,4, Prabhat Kumar5,6
1Institute of Biophysics, Biological Research Center, Szeged, Hungary.
Abstract:
Senescence is a complicated, multi-factorial, irreversible cell cycle halt that has a tumor-suppressing effect in addition to being a significant factor in aging and neurological diseases. Damaged DNA, neuroinflammation, oxidative stress and disrupted proteostasis are a few of the factors that cause senescence. Senescence is triggered by DNA damage which initiates DNA damage response. The DNA damage response, which includes the formation of DNA damage foci containing activated H2AX, which is a key factor in cellular senescence, is provoked by a double strand DNA break. Oxidative stress impairs cognition, inhibits neurogenesis, and has an accelerated aging effect. Senescent cells generate pro-inflammatory mediators known as senescence-associated secretory phenotype (SASP). These pro-inflammatory cytokines and chemokines have an impact on neuroinflammation, neuronal death, and cell proliferation. While it is tempting to think of neurodegenerative diseases as manifestations of accelerated aging and senescence, this review will present information on brain ageing and neurodegeneration as a result of senescence and DNA damage response.
Insights
Cellular senescence, an irreversible cell cycle arrest, contributes to aging and neurological diseases. DNA damage response and senescence-associated secretory phenotype drive neuroinflammation and neurodegeneration.
Area of Science:
- Cellular Biology
- Neuroscience
- Aging Research
Background:
- Cellular senescence is an irreversible cell cycle arrest implicated in aging and neurological diseases.
- Factors like DNA damage, neuroinflammation, and oxidative stress trigger senescence.
- Senescence involves DNA damage response and the release of pro-inflammatory factors (SASP).
Purpose of the Study:
- To explore the role of senescence and DNA damage response in brain aging and neurodegeneration.
- To elucidate the mechanisms linking cellular senescence to neurological dysfunction.
- To provide a comprehensive review of senescence's impact on the brain.
Main Methods:
- Review of existing literature on cellular senescence, DNA damage response, and neurodegeneration.
- Analysis of the molecular pathways involved in senescence induction.
- Examination of the senescence-associated secretory phenotype (SASP) and its inflammatory effects.
Main Results:
- DNA damage triggers a DNA damage response, a key event in cellular senescence.
- Oxidative stress, a factor in senescence, negatively impacts cognition and neurogenesis.
- Senescent cells release SASP, contributing to neuroinflammation and neuronal death.
Conclusions:
- Senescence and DNA damage response are significant contributors to brain aging and neurodegeneration.
- SASP exacerbates neuroinflammation, neuronal loss, and proliferation issues.
- Understanding senescence mechanisms is crucial for addressing age-related neurological decline.
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