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ORIGINAL RESEARCH article
Front. Aging Neurosci.
Sec. Cellular and Molecular Mechanisms of Brain-aging
Volume 16 - 2024 |
doi: 10.3389/fnagi.2024.1503336
Urolithin A and nicotinamide riboside differentially regulate innate immune defences and metabolism in human microglial cells
Provisionally accepted- 1 University of Copenhagen, Copenhagen, Capital Region of Denmark, Denmark
- 2 National Institute on Aging (NIH), Bethesda, Maryland, United States
During aging, many cellular processes, such as autophagic clearance, DNA repair, mitochondrial health, metabolism, nicotinamide adenine dinucleotide (NAD+) levels, and immunological responses, become compromised. Urolithin A (UA) and Nicotinamide Riboside (NR) are two naturally occurring compounds known for their anti-inflammatory and mitochondrial protective properties, yet the effects of these natural substances on microglia cells have not been thoroughly investigated. As both UA and NR are considered safe dietary supplements, it is equally important to understand their function in normal cells and in disease states. This study investigates the effects of UA and NR on immune signalling, mitochondrial function, and microglial activity in a human microglial cell line (HMC3). Both UA and NR were shown to reduce DNA damage-induced cellular senescence. However, they differentially regulated gene expression related to neuroinflammation, with UA enhancing cGAS-STING pathway activation and NR displaying broader anti-inflammatory effects. Furthermore, UA and NR differently influenced mitochondrial dynamics, with both compounds improving mitochondrial respiration but exhibiting distinct effects on production of reactive oxygen species and glycolytic function. These findings underscore the potential of UA and NR as therapeutic agents in managing neuroinflammation and mitochondrial dysfunction in neurodegenerative diseases.
Keywords: nicotinamide riboside, Urolithin A, Microglia, mitochondrial health, innate immune signalling, Aging
Received: 28 Sep 2024; Accepted: 04 Nov 2024.
Copyright: © 2024 Madsen, Navarro, Gasparini, Park, Li, Croteau and Bohr. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Vilhelm Bohr, University of Copenhagen, Copenhagen, 1017, Capital Region of Denmark, Denmark
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