Reduced Versus Oxidized NAD⁺ Precursors Drive Distinct Transcriptomic, Proteomic, and Metabolic Profiles in...

Area of Science:

• Biochemistry
• Cellular Metabolism
• Aging Research

Background:

• Nicotinamide adenine dinucleotide (NAD+) is crucial for cellular functions and declines with age.
• Current NAD+ precursors like NMN and NR have limited boosting capacity.
• Reduced NAD+ precursors (NMNH, NRH) are potent boosters but poorly understood.

Purpose of the Study:

• To comprehensively compare the effects of reduced NAD+ precursors (NMNH, NRH) with their oxidized forms (NMN, NR).
• To investigate the metabolic and transcriptional impacts of these NAD+ precursors in murine hepatocytes.
• To characterize the unique properties of NMNH and NRH as NAD+ boosters.

Main Methods:

• Comparative analysis using RNA sequencing, proteomics, and metabolomics.
• Treatment of cultured murine hepatocytes with NMN, NMNH, NR, and NRH.
• Global metabolic profiling and gene expression analysis.

Main Results:

• NRH and NMNH induced broader metabolic alterations than NR and NMN.
• NRH uniquely suppressed energy metabolism-related metabolites.
• Reduced precursors triggered more differentially expressed genes, including stress-related GSTs, without causing oxidative stress.

Conclusions:

• Reduced NAD+ precursors (NMNH, NRH) are distinct and more potent NAD+ boosters than NMN and NR.
• NMNH and NRH influence a wider array of cellular processes beyond NAD+ boosting.
• These findings highlight the unique therapeutic potential of reduced NAD+ precursors in aging and metabolic research.