Aging is a complex biological process with significant impacts on the central nervous system (CNS), often contributing to neurological disorders, particularly neurodegenerative diseases. A key contributor to these age-related brain changes is neuroinflammation—a chronic, low-grade inflammation within the CNS.

Research has increasingly highlighted the importance of sex differences in the onset, progression, and outcomes of neuroinflammatory processes. These differences stem from a complex interaction of genetic, hormonal, and environmental influences, resulting in distinct immune and CNS responses in males and females. For example, the prevalence and severity of neurodegenerative diseases such as Alzheimer's, which affects more women, and Parkinson's, more common in men, demonstrate these sex-specific mechanisms. Understanding these mechanisms is critical, especially given the inconsistencies between findings in rodent models and human studies, and the potential impact on cognitive decline associated with aging or disease.

Understanding the sex-specific modulation of neuroinflammation during aging is crucial for developing targeted therapeutic strategies. By elucidating the mechanisms underlying these differences, researchers can better address the unique needs of aging populations, ultimately improving outcomes for age-related neurological disorders. This area of research holds promise for advancing personalized medicine approaches in the treatment and prevention of age-related neurodegenerative diseases.

This Research Topic seeks to collect recent advancements and ongoing studies focused on the molecular mechanisms governing sex-specific neuroinflammation and related disorders. We aim to gather both basic science and clinical research, offering comprehensive insights to guide medical professionals in mitigating neuroinflammation-related neurological and neurodegenerative diseases, with an emphasis on sex differences.

We invite articles that explore, but are not limited to, the following topics:

1. The role of sex as a biological variable in neuroinflammation during aging.

2. Sex-specific modulation of immune metabolism and its impact on cognitive function, including:

i. Innate and neural immune mechanisms

ii. Adaptive immune and neural immune mechanisms

iii. Neurovascular integrity

iv. Glymphatic and meningeal lymphatic system

v. Mitochondrial homeostasis and cellular metabolism

3. The effect of sex hormones on neuroinflammatory responses.

4. The effect of sex on the microbiota and gut-brain axis-mediated regulation of neuroinflammation.

5. The effect of sex on early life inflammation and its relationship to late-life neurodegeneration.

Dr Celia Giulietta Fernandez is employed by Recursion Pharmaceuticals.

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Frontiers in Aging Neuroscience

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