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Updated: Oct 31, 2025
Semi-Targeted Ultra-High-Performance Chromatography Coupled to Mass Spectrometry Analysis of Phenolic Metabolites in Plasma of Elderly Adults
Published on: April 22, 2022
Polyphenol Supplementation Reverses Age-Related Changes in Microglial Signaling Cascades
Ahmad Jalloh1, Antwoine Flowers1, Charles Hudson2
1Center of Excellence for Aging and Brain Repair, Departments of Neurosurgery and Brain Repair, and Molecular Pharmacology and Physiology, USF Morsani College of Medicine, 12901 Bruce B. Downs Blvd, MDC 78, Tampa, FL 33612, USA.
Abstract:
Microglial activity in the aging neuroimmune system is a central player in aging-related dysfunction. Aging alters microglial function via shifts in protein signaling cascades. These shifts can propagate neurodegenerative pathology. Therapeutics require a multifaceted approach to understand and address the stochastic nature of this process. Polyphenols offer one such means of rectifying age-related decline. Our group used mass spectrometry (MS) analysis to explicate the complex nature of these aging microglial pathways. In our first experiment, we compared primary microglia isolated from young and aged rats and identified 197 significantly differentially expressed proteins between these groups. Then, we performed bioinformatic analysis to explore differences in canonical signaling cascades related to microglial homeostasis and function with age. In a second experiment, we investigated changes to these pathways in aged animals after 30-day dietary supplementation with NT-020, which is a blend of polyphenols. We identified 144 differentially expressed proteins between the NT-020 group and the control diet group via MS analysis. Bioinformatic analysis predicted an NT-020 driven reversal in the upregulation of age-related canonical pathways that control inflammation, cellular metabolism, and proteostasis. Our results highlight salient aspects of microglial aging at the level of protein interactions and demonstrate a potential role of polyphenols as therapeutics for age-associated dysfunction.
Insights
Aging alters brain immune cells called microglia, impacting function and potentially causing neurodegeneration. Polyphenols, like those in NT-020, may reverse these age-related changes in microglial pathways.
Area of Science:
- Neuroimmunology
- Aging Research
- Cellular Biology
Background:
- Microglial cells are key to brain immune function and are significantly altered during aging.
- These age-related changes in microglial function can disrupt neuroimmune homeostasis and contribute to neurodegenerative pathology.
- Understanding the molecular mechanisms underlying microglial aging is crucial for developing effective therapeutics.
Purpose of the Study:
- To investigate the proteomic changes in microglia during aging.
- To explore the impact of polyphenol supplementation (NT-020) on aging-related microglial pathways.
- To identify potential therapeutic targets for mitigating age-associated neuroimmune decline.
Main Methods:
- Mass spectrometry (MS) was used to compare protein expression in primary microglia from young and aged rats.
- Bioinformatic analysis was performed to identify differentially expressed proteins and altered canonical signaling pathways.
- Aged rats were supplemented with NT-020 (a polyphenol blend) or a control diet, followed by MS analysis of microglia.
Main Results:
- 197 proteins were significantly differentially expressed between young and aged rat microglia.
- 144 proteins were differentially expressed in aged rats supplemented with NT-020 compared to controls.
- Bioinformatic analysis indicated that NT-020 reversed age-related pathway upregulation in inflammation, metabolism, and proteostasis.
Conclusions:
- Aging profoundly impacts microglial protein expression and signaling pathways.
- Polyphenol supplementation with NT-020 shows potential in reversing age-associated microglial dysfunction.
- These findings highlight polyphenols as a promising therapeutic strategy for age-related neuroimmune decline.
