Co-treatment of nicotinamide mononucleotide and neoagarooligosaccharide mitigates aging-induced cognitive impairment by promoting mitochondrial dynamics

Abstract

The synergistic effects of nicotinamide mononucleotide (NMN) and neoagarooligosaccharides (NAOS) on mitochondrial dysfunction, downstream apoptosis, and inflammation were evaluated in both senescence-accelerated mouse prone 8 (SAMP8) mice and H2O2-induced human lung fibroblast (MRC-5) cells. Co-treatment of NMN and NAOS effectively ameliorated the learning and memory impairment in the passive avoidance and the Morris water maze tests. MNN and NAOS supplementation increased the expression levels of mitochondrial fusion proteins in the brain of SAMP8 mice, including OPA1 (by 37.4%) and Mitofusin 2 (by 99.7%). Moreover, co-treatment of NMN and NAOS significantly inhibited cell apoptosis as shown by the reduced protein expression levels of Bax and Caspase-3, down-regulated P53/P21/P16 pathway in both SAMP8 mice and H2O2-induced MRC-5 cells. At the same time, dietary intervention of NMN combined with NAOS attenuated the inflammatory response via down-regulating TLR4/MyD88/NF-κB pathway. Conclusively, the synergistic efficacy of the combination of NMN and NAOS can improve cognitive impairment by modulating mitochondrial dysfunction.

Keywords

• Aging
• Nicotinamide mononucleotide
• Neoagarooligosaccharides
• Cognitive impairment
• Mitochondrial dysfunction