Supplementation with NMN diminishes cognitive impairments triggered by sepsis-induced inflammation by activating the anti-ageing-linked enzyme SIRT1 in rodents.NMN reduces inflammation-induced oxidative stress, which causes cellular damage to organs and tissues. The human immune system is a remarkable defence mechanism like none other. It works tirelessly to safeguard against infections and diseases. Alas, it is far from perfect, as dysregulation or overstimulation can often cause the immune system to inflict serious harm on our bodies. Particularly, excessive inflammation may result in cognitive impairments. However, exciting research conducted by scientists at the Naval Medical University in China has shed light on a potential solution: Nicotinamide Mononucleotide (NMN). This latest study explores how the NMN supplement benefits us in fighting brain inflammation and activates the longevity-associated enzyme SIRT1, offering promising anti-inflammatory and anti-ageing benefits. NMN and SIRT1 Activation for Cognitive Improvement In their study, Li and colleagues delved into the effects of NMN on septic mice, a life-threatening condition triggered by an infection that leads to systemic inflammation. The scientists provoked sepsis in mice by perforating their cecum and releasing bacteria into their bloodstream, leading to septic shock. The results revealed that septic mice exhibited reduced levels of NAD+ and SIRT1 in their hippocampus, a brain region responsible for memory consolidation. Since NMN is known to restore NAD+ levels and activate SIRT1, the researchers administered NMN to the septic mice. The treatment successfully elevated both NAD+ and SIRT1 levels in the hippocampus due to NMN’s ability to penetrate the blood-brain barrier. For evaluating the cognitive abilities of septic mice, the researchers employed the Morris water maze test, which assesses spatial learning and memory. The results revealed that the septic mice performed poorly in the maze, making more errors and taking longer to find the escape platform than normal mice. These findings indicated disruptions in the hippocampus-mediated learning and memory of septic mice. However, when the septic mice received NMN supplementation, the benefits of NMN were evident. It caused improved performance in the maze, suggesting enhanced cognition due to NMN supplementation. NMN’s Impact on Brain Inflammation and Oxidative Stress The researchers also investigated how NMN improved cognition in septic mice by evaluating hippocampus inflammation and oxidative stress. Oxidative stress results from excessive reactive oxygen species (ROS) production, damaging proteins, lipid membranes, and DNA. Inflammation is known to trigger oxidative stress. In the hippocampus of septic mice, the findings showed a significant increase in proinflammatory molecules, including IL-6 and ROS levels. However, NMN administration dramatically reduced these, showcasing its potent anti-inflammatory and antioxidant properties. The Role of SIRT1 in NMN Supplement Benefits Sirtuin 1 (SIRT1) is an enzyme that utilizes NAD+ as fuel. With sufficient fuel, SIRT1 can initiate various processes associated with longevity. For instance, over-activating SIRT1 in the hypothalamus has been demonstrated to prolong the lifespan of mice. To test if SIRT1 mediates NMN’s effects on septic mice, the researchers conducted experiments inhibiting SIRT1 activity using a drug. The results revealed that blocking SIRT1 hindered NMN’s cognitive-enhancing, anti-oxidative, and anti-inflammatory effects, indicating its critical role in NMN supplement benefits. NMN as a Potential Anti-Inflammatory Agent The study’s findings imply that NMN may effectively reduce brain inflammation and improve cognitive impairments linked to hippocampal inflammation. Although sepsis is a serious inflammatory condition, inflammation can also arise from injuries and the natural ageing process. Inflammaging, which involves chronic low-grade inflammation associated with ageing, is thought to play a role in various chronic diseases, including neurodegenerative conditions. Additionally, certain foods and environmental toxins can sometimes trigger brain inflammation. Notably, NMN has shown the potential to reduce inflammation not only in the brain but also in rat’s lungs, skin, gut, heart, and fat tissue. NMN supplementation benefits mitochondrial health, which is essential for decreasing ROS generation within cells by activating SIRT1 through NAD+ production. Additionally, increasing NAD+ levels in immune cells help restore balance to a dysregulated immune system by reducing inflammation. Consequently, NMN could restore energy homeostasis in affected cells and relieve inflamed tissues when inflammation occurs improperly. NMN: Anti-Inflammatory and Anti-Ageing Brain Supplement Through activation of SIRT1 and restoration of NAD+ levels, NMN effectively combats brain inflammation, reduces oxidative stress, and improves memory in septic mice. These findings offer hope for developing NMN as a powerful anti-ageing brain supplement, with potential applications in combating inflammaging and age-related chronic diseases. Further research in human trials may unlock the full therapeutic potential of NMN, making it a promising candidate for future anti-inflammatory therapies and cognitive health support.