2022
DOI: 10.1002/glia.24282
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Is microglial dystrophy a form of cellular senescence? An analysis of senescence markers in the aged human brain

Abstract: Aging can cause morphological transformation in human microglia indicative of cell senescence, termed microglial dystrophy. However, cellular senescence is characterized by additional changes, such as an irregular cell cycle arrest, and a variety of metabolic and molecular changes including a senescence-associated secretory phenotype, dysfunction of degradation mechanisms, and altered DNA damage response. Here, we tested whether dystrophic microglia display customary markers of cell senescence by performing do… Show more

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Cited by 25 publications
(18 citation statements)
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“…While it is not significantly enriched in any individual spatial domain comprising the DG, it is enriched in the composite DG in the elderly group ( Table S3 ). Inflammatory stimuli can induce iron accumulation in microglia and neurons in vitro via hepcidin and related molecules 74 , which is important because iron overloading is consistently observed in aging microglia that express a senescent or dystrophic phenotype 51,52 .…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…While it is not significantly enriched in any individual spatial domain comprising the DG, it is enriched in the composite DG in the elderly group ( Table S3 ). Inflammatory stimuli can induce iron accumulation in microglia and neurons in vitro via hepcidin and related molecules 74 , which is important because iron overloading is consistently observed in aging microglia that express a senescent or dystrophic phenotype 51,52 .…”
Section: Resultsmentioning
confidence: 99%
“…Inflammation is associated with blood-brain barrier (BBB) permeability, and human functional magnetic resonance imaging (fMRI) studies suggest pronounced aging-related increases in BBB permeability at the DG 34 . In aged rodents, neuroblasts adopt a senescence-associated secretory phenotype that induces auto-inflammation 35 , while glial cells, including microglia and astrocytes, undergo age-dependent increases in neuroinflammation in the DG, which decreases neurogenesis and exacerbates degeneration 33,[36][37][38][39][40][41][42][43][44] . Importantly, activated microglia can induce reactive astrocytes 39 , triggering further inflammation and neurodegeneration.…”
mentioning
confidence: 99%
“…Microglia display substantial changes with aging, including changes in gene expression, ultrastructure, and the epigenome which affect their morphology, liposomal dysfunction (increased accumulation of lipofuscin and senescence-associated β-galoctosidase expression), and promote dysregulation of cell cycle protein machinery, including proteins p53, p21, and p14 Ink4a [reviewed in [28]]. These cells have been described in the literature as dystrophic or senescent and accumulate over time during normal brain aging [29]. Profound changes in transcriptional profiles with aging also result in secretion of various pro-inflammatory cytokines, a phenomenon referred to as senescence-associated secretory phenotype [28,30], characterized by increased secretion of IL-1, IL-6, and decreased secretion of various growth factors necessary for neuronal support.…”
Section: Age-related Changes In Microgliamentioning
confidence: 99%
“…In the healthy brain, microglia are the resident immune cells and are essential for proper brain functioning and homeostasis (6). However, microglia adopt a dystrophic morphology in postmortem brain samples from elderly donors (7)(8)(9). Additionally, in in vivo and in vitro mouse studies, microglia show defective functionality including reduced surveillance and phagocytic activity, increased production of reactive oxygen species (10,11), reduced response to insults (12), slower migration to sites of infection and processes shrinkage (13).…”
Section: Introductionmentioning
confidence: 99%