Ageing-related changes in the regulation of microglia and their interaction with neurons
Rommy von Bernhardi1, Jaime Eugenín2
1Universidad San Sebastian, Faculty for Odontology and Rehabilitation Sciences. Lota 2465, Providencia, Santiago, PO. 7510602, Chile.
Abstract:
Ageing is one of the most important risk factors for chronic health conditions, including neurodegenerative diseases. Inflammation is a feature of ageing, as well as a key pathophysiological mechanism for degenerative diseases. Microglia play multiple roles in the central nervous system; their states entail a complex assemblage of responses reflecting the multiplicity of functions they fulfil both under homeostatic basal conditions and in response to stimuli. Whereas glial cells can promote neuronal homeostasis and limit neurodegeneration, age-related inflammation (i.e. inflammaging) leads to the functional impairment of microglia and astrocytes, exacerbating their response to stimuli. Thus, microglia are key mediators for age-dependent changes of the nervous system, participating in the generation of a less supportive or even hostile environment for neurons. Whereas multiple changes of ageing microglia have been described, here we will focus on the neuron-microglia regulatory crosstalk through fractalkine (CX3CL1) and CD200, and the regulatory cytokine Transforming Growth Factor β1 (TGFβ1), which is involved in immunomodulation and neuroprotection. Ageing results in a dysregulated activation of microglia, affecting neuronal survival, and function. The apparent unresponsiveness of aged microglia to regulatory signals could reflect a restriction in the mechanisms underlying their homeostatic and reactive states. The spectrum of functions, required to respond to life-long needs for brain maintenance and in response to disease, would progressively narrow, preventing microglia from maintaining their protective functions. This article is part of the Special Issue on "Microglia".
Insights
Aging impairs microglia, the brain's immune cells, leading to neuroinflammation and reduced neuronal support. This age-related dysfunction affects brain health and increases susceptibility to neurodegenerative diseases.
Area of Science:
- Neuroscience
- Immunology
- Aging Research
Background:
- Aging is a major risk factor for neurodegenerative diseases, with inflammation playing a key role.
- Microglia, the central nervous system's immune cells, have complex roles in maintaining brain homeostasis and responding to stimuli.
- Age-related inflammation, or inflammaging, impairs microglial function, creating a less supportive environment for neurons.
Purpose of the Study:
- To examine the impact of aging on microglia function and their regulatory crosstalk with neurons.
- To focus on the neuron-microglia communication pathways involving fractalkine (CX3CL1), CD200, and Transforming Growth Factor β1 (TGFβ1).
Main Methods:
- Review of existing literature on microglial function in aging.
- Analysis of molecular signaling pathways regulating neuron-microglia interactions.
Main Results:
- Aging leads to dysregulated microglial activation, negatively impacting neuronal survival and function.
- Impaired microglia exhibit reduced responsiveness to regulatory signals, limiting their protective capabilities.
- Age-related changes narrow the functional spectrum of microglia, hindering their ability to maintain brain health and respond to disease.
Conclusions:
- Microglia are central mediators of age-dependent nervous system changes.
- Dysfunctional microglia contribute to neuroinflammation and neurodegeneration in aging.
- Targeting neuron-microglia communication pathways may offer therapeutic strategies for age-related neurological decline.
