Senescent Microglia: The Key to the Ageing Brain?

Greenwood, Eleanor K.; Brown, David R.

doi:10.3390/ijms22094402

Cited by 33 publications

(11 citation statements)

References 210 publications

(287 reference statements)

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“…Furthermore, profound modifications in the transcriptome profile, secretome, morphology, and phagocytic activity of aged microglia are associated with the housekeeping and defensive functions of microglia [69]. In addition, the functional properties of senescent microglial changes are sex specific [70], and changes in energy metabolism are considered responsible for their reduced phagocytotic capacity [71].…”

Section: Senescent Microgliamentioning

confidence: 99%

Microglia and the Aging Brain: Are Geriatric Microglia Linked to Poor Sleep Quality?

Choudhury

Miyanishi

Tamano

et al. 2021

IJMS

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Poor sleep quality and disrupted circadian behavior are a normal part of aging and include excessive daytime sleepiness, increased sleep fragmentation, and decreased total sleep time and sleep quality. Although the neuronal decline underlying the cellular mechanism of poor sleep has been extensively investigated, brain function is not fully dependent on neurons. A recent antemortem autographic study and postmortem RNA sequencing and immunohistochemical studies on aged human brain have investigated the relationship between sleep fragmentation and activation of the innate immune cells of the brain, microglia. In the process of aging, there are marked reductions in the number of brain microglial cells, and the depletion of microglial cells disrupts circadian rhythmicity of brain tissue. We also showed, in a previous study, that pharmacological suppression of microglial function induced sleep abnormalities. However, the mechanism underlying the contribution of microglial cells to sleep homeostasis is only beginning to be understood. This review revisits the impact of aging on the microglial population and activation, as well as microglial contribution to sleep maintenance and response to sleep loss. Most importantly, this review will answer questions such as whether there is any link between senescent microglia and age-related poor quality sleep and how this exacerbates neurodegenerative disease.

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Section: Senescent Microgliamentioning

confidence: 99%

Microglia and the Aging Brain: Are Geriatric Microglia Linked to Poor Sleep Quality?

Choudhury

Miyanishi

Tamano

et al. 2021

IJMS

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“…However, in a reactionary or dystrophic state, microglia also contribute to the pathogenesis of various NDs and post-TBI syndromes [43][44][45]. The overlapping phenotypes of reactive and senescent microglia together with the heterogeneity of microglial phenotypes described in ageing and disease [45,46] present a nuanced challenge to defining senescent microglia and parsing out their contribution to dysfunction.…”

Section: Introductionmentioning

confidence: 99%

Untangling senescent and damage‐associated microglia in the aging and diseased brain

McNeely

Baker

2021

The FEBS Journal

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Microglial homeostasis has emerged as a critical mediator of health and disease in the central nervous system. In their neuroprotective role as the predominant immune cells of the brain, microglia surveil the microenvironment for debris and pathogens, while also promoting neurogenesis and performing maintenance on synapses. Chronological ageing, disease onset, or traumatic injury promotes irreparable damage or deregulated signaling to reinforce neurotoxic phenotypes in microglia. These insults may include cellular senescence, a stable growth arrest often accompanied by the production of a distinctive pro-inflammatory secretory phenotype, which may contribute to age-or disease-driven decline in neuronal health and cognition and is a potential novel therapeutic target. Despite this increased scrutiny, unanswered questions remain about what distinguishes senescent microglia and non-senescent microglia reacting to insults occurring in ageing, disease, and injury, and how central the development of senescence is in their pivot from guardian to assailant. To intelligently design future studies to untangle senescent microglia from other primed and reactionary states, specific criteria must be developed that define this population and allow for comparisons between different model systems. Comparing microglial activity seen in homeostasis, ageing, disease, and injury allows for a more coherent understanding of when and how senescent and other harmful microglial subpopulations should be targeted.

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“…The aging brain, in turn, appears to be able to influence the immune system and promote immune cell recruitment from the periphery, contributing to immunosenescence and neuroinflammation. Furthermore, the age-related decrease in anti-inflammatory molecules adds to increased sensitivity to both extrinsic and intrinsic stresses [99][100][101][102]. Even in neurologically intact elderly people, overproduction of pro-inflammatory mediators in the periphery may cause a progressive increase in neuroinflammation, characterized by increased glial activation, elevated steady-state levels of inflammatory cytokines, and decreased production of anti-inflammatory molecules [85].…”

Section: Microglia In Brain Aging and Inflammagingmentioning

confidence: 99%

Inflammaging and Brain: Curcumin and Its Beneficial Potential as Regulator of Microglia Activation

et al. 2022

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Inflammaging is a term used to describe the tight relationship between low-grade chronic inflammation and aging that occurs during physiological aging in the absence of evident infection. This condition has been linked to a broad spectrum of age-related disorders in various organs including the brain. Inflammaging represents a highly significant risk factor for the development and progression of age-related conditions, including neurodegenerative diseases which are characterized by the progressive dysfunction and degeneration of neurons in the brain and peripheral nervous system. Curcumin is a widely studied polyphenol isolated from Curcuma longa with a variety of pharmacologic properties. It is well-known for its healing properties and has been extensively used in Asian medicine to treat a variety of illness conditions. The number of studies that suggest beneficial effects of curcumin on brain pathologies and age-related diseases is increasing. Curcumin is able to inhibit the formation of reactive-oxygen species and other pro-inflammatory mediators that are believed to play a pivotal role in many age-related diseases. Curcumin has been recently proposed as a potential useful remedy against neurodegenerative disorders and brain ageing. In light of this, our current review aims to discuss the potential positive effects of Curcumin on the possibility to control inflammaging emphasizing the possible modulation of inflammaging processes in neurodegenerative diseases.

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Senescent Microglia: The Key to the Ageing Brain?

Cited by 33 publications

References 210 publications

Microglia and the Aging Brain: Are Geriatric Microglia Linked to Poor Sleep Quality?

Microglia and the Aging Brain: Are Geriatric Microglia Linked to Poor Sleep Quality?

Untangling senescent and damage‐associated microglia in the aging and diseased brain

Inflammaging and Brain: Curcumin and Its Beneficial Potential as Regulator of Microglia Activation

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