Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain

Spinelli, Chiara; Martucciello, Stefania; Nori, Stefania Lucia; Coccia, Mario; Puca, Annibale Alessandro; Ciaglia, Elena

doi:10.1002/jlb.3mr0118-003r

Cited by 41 publications

(29 citation statements)

References 202 publications

(242 reference statements)

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“…Interestingly, recent studies described that individual microglia have an unexpectedly long life, and a lower turnover rate (Füger et al, 2017;Réu et al, 2017). These results propose an interesting direction for future research, and change our conceptual understanding of microglial functions both in physiological states, and -perhaps more importantly -in the context of aging and neurodegeneration (Olah et al, 2018;Santoro et al, 2018).…”

Section: The Bidirectional Communication Between Microglia and Neuronmentioning

confidence: 84%

New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective

et al. 2019

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Microglia are the primary immune cells of the central nervous system. However, recent data indicate that microglia also contribute to diverse physiological and pathophysiological processes that extend beyond immune-related functions and there is a growing interest to understand the mechanisms through which microglia interact with other cells in the brain. In particular, the molecular processes that contribute to microglia-neuron communication in the healthy brain and their role in common brain diseases have been intensively studied during the last decade. In line with this, fate-mapping studies, genetic models and novel pharmacological approaches have revealed the origin of microglial progenitors, demonstrated the role of self-maintaining microglial populations during brain development or in adulthood, and identified the unexpectedly long lifespan of microglia that may profoundly change our view about senescence and age-related human diseases. Despite the exponentially increasing knowledge about microglia, the role of these cells in health and disease is still extremely controversial and the precise molecular targets for intervention are not well defined. This is in part due to the lack of microglia-specific manipulation approaches until very recently and to the high level of complexity of the interactions between microglia and other cells in the brain that occur at different temporal and spatial scales. In this review, we briefly summarize the known physiological roles of microglia-neuron interactions in brain homeostasis and attempt to outline some major directions and challenges of future microglia research.

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Section: The Bidirectional Communication Between Microglia and Neuronmentioning

confidence: 84%

New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective

et al. 2019

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“…Additionally, aging also alters the immune system, which is subsequently leading to inflammaging. Adaptive immunity decreases with age; conversely, innate immunity demonstrated minute changes in mild hyperactivity (Santoro et al, 2018 ). The response of innate immunity might increase when adaptive immunosenescence progresses.…”

Section: Chronic Inflammation and Aging (Inflammaging)mentioning

confidence: 99%

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

et al. 2018

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Aging is the progressive loss of organ and tissue function over time. Growing older is positively linked to cognitive and biological degeneration such as physical frailty, psychological impairment, and cognitive decline. Oxidative stress is considered as an imbalance between pro- and antioxidant species, which results in molecular and cellular damage. Oxidative stress plays a crucial role in the development of age-related diseases. Emerging research evidence has suggested that antioxidant can control the autoxidation by interrupting the propagation of free radicals or by inhibiting the formation of free radicals and subsequently reduce oxidative stress, improve immune function, and increase healthy longevity. Indeed, oxidation damage is highly dependent on the inherited or acquired defects in enzymes involved in the redox-mediated signaling pathways. Therefore, the role of molecules with antioxidant activity that promote healthy aging and counteract oxidative stress is worth to discuss further. Of particular interest in this article, we highlighted the molecular mechanisms of antioxidants involved in the prevention of age-related diseases. Taken together, a better understanding of the role of antioxidants involved in redox modulation of inflammation would provide a useful approach for potential interventions, and subsequently promoting healthy longevity.

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“…In the brain, the innate immune system is responsible for the detection and removal of invading microorganisms, senescent cells, surplus neurotransmitters, and aged and glycated proteins, which allows the maintenance of a healthy microenvironment [33]. Generally, in response to homeostatic disruption or signals released during normal development, these cells locally produce virtually all complement components, in addition to expressing complement receptors and the Toll-like receptors (TLRs) system [34].…”

Section: Neuroinflammatory Cross-talk In Response To Brain Lesions Anmentioning

confidence: 99%

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

Chagas

Sandre

Ribeiro

et al. 2020

IJMS

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Recent discoveries on the neurobiology of the immunocompetent cells of the central nervous system (CNS), microglia, have been recognized as a growing field of investigation on the interactions between the brain and the immune system. Several environmental contexts such as stress, lesions, infectious diseases, and nutritional and hormonal disorders can interfere with CNS homeostasis, directly impacting microglial physiology. Despite many encouraging discoveries in this field, there are still some controversies that raise issues to be discussed, especially regarding the relationship between the microglial phenotype assumed in distinct contexts and respective consequences in different neurobiological processes, such as disorders of brain development and neuroplasticity. Also, there is an increasing interest in discussing microglial-immune system cross-talk in health and in pathological conditions. In this review, we discuss recent literature concerning microglial function during development and homeostasis. In addition, we explore the contribution of microglia to synaptic disorders mediated by different neuroinflammatory outcomes during pre-and postnatal development, with long-term consequences impacting on the risk and vulnerability to the emergence of neurodevelopmental, neurodegenerative, and neuropsychiatric disorders.

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Innate immunity and cellular senescence: The good and the bad in the developmental and aged brain

Cited by 41 publications

References 202 publications

New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective

New Insights into Microglia–Neuron Interactions: A Neuron’s Perspective

Antioxidant and Oxidative Stress: A Mutual Interplay in Age-Related Diseases

Environmental Signals on Microglial Function during Brain Development, Neuroplasticity, and Disease

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