Interplay between Peripheral and Central Nervous System Myeloid Cells during Aging: Impact for Lade-Life Depression and Alzheimer’s Disease
Year: 2026
Type: article
Abstract: BACKGROUND: Aging is associated with enumerative and functional changes of peripheral innate immune cells, notably myeloid cells (e.g., monocytes/macrophages and neutrophils). Peripheral myeloid cells routinely infiltrate the brain, particularly at the brain borders, influencing cognition, mood, and stress responses. SUMMARY: Here, we review how the dysfunctional crosstalk between circulating myeloid cells and brain cells may contribute to the development of late-life depression and Alzheimer's disease during aging. The aged cerebral microglia (i.e., resident macrophages) exhibit dystrophic morphology and impaired phagocytosis while peripheral myeloid cells expand in number but display functional deficits, including impaired phagocytosis and pro-inflammatory biased response. The peripheral myeloid changes collectively contribute to systemic chronic inflammation and tissue dysfunction. Epigenetic changes and metabolic disruptions, such as altered glucose utilization, exacerbate pro-inflammatory states. KEY MESSAGES: The cumulative impact of these alterations undermines neuroprotection and facilitates age-related neuropsychiatric conditions, including neurodegenerative diseases and late-life depression. The identification of pro-aging circulating factors and cells could pave the way for new therapeutic strategies aimed at mitigating cognitive decline and improving mood. Targeting myeloid cell metabolism or inflammatory signaling pathways emerges as a promising strategy to mitigate aging-associated neuropsychiatric syndromes.
Source: NeuroImmunoModulation
DOI: 10.1159/000550781
Institutions: Universidade Federal de Minas Gerais, Centre for Addiction and Mental Health, University of Toronto, The University of Texas at San Antonio Health Science Center, Conselho Nacional de Desenvolvimento Científico e Tecnológico, Instituto Nacional de Ciência e Tecnologia em Neuroimunomodulação, Pontifícia Universidade Católica do Rio Grande do Sul
Language: English
Subfield: Neurology
Field: Neuroscience
Domain: Life Sciences
Open Access status: diamond
OpenAlex ID: W7127940007