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Endothelial cells, pericytes, and astrocytes in the aging brain can become senescent and express characteristic SASP proteins, including various species of potentially neurotoxic factors, which may disrupt functional neurovascular coupling and induce BBB damage.
In this Review, we will discuss what constitutes senescence, the evidence implicating senescence in dysfunction of the CNS, and how senescent cells may be targeted for the development of novel therapeutics to treat pathologies associated with brain aging.
Within the brain, senescent cells have been associated with a variety of diseases, including Parkinson’s and Alzheimer’s disease, and maladies where chronic inflammation drives tissue deterioration.
Senescent cells impact on aging-related changes in the brain. Accumulation of senescent glia cells and neurons lead to structural and functional changes in the brain that result in cognitive impairment. All figures were prepared using BioRender.com.
Strikingly, interventions targeting senescent cells have demonstrated significant promise in delaying dysfunction and extending health span (Chaib et al., 2022). Different cell types are shown to accumulate in the aging brain, each with unique characteristics and functions.
Accumulation of DNA damage and senescent cells triggers neuroinflammation in brain aging. Single-cell whole-genome sequencing of the normal human brain revealed a drastic accumulation of neuronal genome-wide somatic single-nucleotide variants (sSNV) with advancing age, especially in the dentate gyrus [18].
Proliferation-competent glial cells can undergo senescence both in vitro and in vivo, and they likely participate in neuroinflammation, which is characteristic for the aging brain. However, apart from proliferation-competent glial cells, the brain consists of post-mitotic neurons.
White matter makes up most of your brain. You lose a lot of it with age. That can cause thinking, walking, and balance problems. WebMD tells you how to prevent it.
Highlights. Accumulation of DNA damage and senescent cells can trigger neuroinflammation in the aging brain. During brain aging, intrinsic cells of the central nervous system (CNS) such as neurons, astrocytes, oligodendrocytes, and microglia display spatial heterogeneity and sex differences, and contribute to neuroinflammation.
A new report details how, with aging, changes in the dentate gyrus microenvironment lead to natural-killer-cell-mediated clearance of neurogenic senescent cells, resulting in cognitive...