Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice
Orally Administered NMN Increases Plasma NMN and Tissue NAD+ Levels
What is Astareal
Natural astaxanthin has a unique molecular structure that makes it literally hundreds of times stronger than any other antioxidant molecule. For this reason, astaxanthin is often called “The King of Antioxidants”.
Long-Term Administration of Nicotinamide Mononucleotide Mitigates Age-Associated Physiological Decline in Mice.
NAD+ availability decreases with age and in certain disease conditions. Nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to enhance NAD+ biosynthesis and ameliorate various pathologies in mouse disease models.
A conserved NAD+ binding pocket that regulates protein-protein interactions during aging
As mice age and NAD+ concentrations decline, DBC1 is increasingly bound to PARP1, causing DNA damage to accumulate, a process rapidly reversed by restoring the abundance of NAD+. Thus, NAD+ directly regulates protein-protein interactions, the modulation of which may protect against cancer, radiation, and aging.
From discoveries in ageing research to therapeutics for healthy ageing
The fact that NAD+ levels increase under conditions that increase lifespan and healthspan, such as dietary restriction and exercise, and decrease during ageing or under conditions that decrease lifespan and healthspan, such as a high-fat diet, support the working model that decreased NAD+ levels might contribute to the ageing process. On the basis of this idea, it has been predicted and validated that NAD+ supplementation exerts protective effects during ageing
ROS, Cell Senescence, and Novel Molecular Mechanisms in Aging and Age-Related Diseases
The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS).
Oxidative stress, aging, and diseases.
Reactive oxygen and nitrogen species (RONS) are produced by several endogenous and exogenous processes, and their negative effects are neutralized by antioxidant defenses. Oxidative stress occurs from the imbalance between RONS production and these antioxidant defenses.
Age-Associated Changes In Oxidative Stress and NAD+ Metabolism In Human Tissue
The aging process worsens the human body functions at multiple levels, thus causing its gradual decrease to resist stress, damage, and disease. Besides changes in gene expression and metabolic control, the aging rate has been associated with the production of high levels of Reactive Oxygen Species (ROS) and/or Reactive Nitrosative Species (RNS).
In vivo NAD assay reveals the intracellular NAD contents and redox state in healthy human brain and their age dependences
Furthermore, an age-dependent increase of intracellular NADH and age-dependent reductions in NAD+, total NAD contents, and NAD+/NADH redox potential of the healthy human brain were revealed in this study. The overall findings not only provide direct evidence of declined mitochondrial functions and altered NAD homeostasis that accompany the normal aging process but also, elucidate the merits and potentials of this new NAD assay for noninvasively studying the intracellular NAD metabolism and redox state in normal and diseased human brain or other organs in situ.
De novo NAD+ synthesis enhances mitochondrial function and improves health
Increasing NAD+ levels activates the sirtuins and positively impacts on metabolism in different model organisms1–4. Given the salutary effects of replenished NAD+ pools, there is an intense search for strategies to increase intracellular NAD+ ranging from limiting NAD+ consumption to increasing NAD+ production5.
Enhancement of cysteine catabolism into taurine impacts glutathione homeostasis in rats challenged with ethanol.
However, cysteine dioxygenase was up-regulated rapidly, and hypotaurine/taurine levels were significantly higher than those found in the saline-treated rats. It is therefore suggested that enhancement of cysteine catabolism into taurine contributes to the depletion of hepatic glutathione, which could exacerbate the ethanol-induced oxidative liver injury.
Effect of taurine on ethanol-induced oxidative stress in mouse liver and kidney.
Taurine supplementation has also been shown to attenuate steatosis and hepatotoxicity in several animal models.The main organs involved in taurine metabolism are the gut, liver, and kidneys. The gut regulates taurine uptake from the diet by a specific taurine transporter.The liver is involved in endogenous taurine biosynthesis from methionine or cysteine by their decarboxylation and subsequent oxidation of the sulfhydryl group and in the formation of bile acids containing taurine.Whereas, the kidneys are the main sites of excretion of taurine.
Effect of l-cysteine on acetaldehyde self-administration
Acetaldehyde (ACD), the first metabolite of ethanol, has been implicated in several behavioural actions of alcohol, including its reinforcing effects. Recently, we reported that l-cysteine, a sequestrating agent of ACD, reduced oral ethanol self-administration and that ACD was orally self-administered.
Effects of ALDH2 Genotype, PPI Treatment and L-Cysteine on Carcinogenic Acetaldehyde in Gastric Juice and Saliva after Intragastric Alcohol Administration
A capsule that slowly releases L-cysteine effectively eliminated acetaldehyde from the gastric juice of PPI-treated ALDH2-active and ALDH2-deficient subjects. These results provide entirely novel perspectives for the prevention of gastric cancer, especially in established risk groups.
Detection of Acetaldehyde in the Esophageal Tissue among Healthy Male Subjects after Ethanol Drinking and Subsequent L-Cysteine Intake
In conclusion, we detected acetaldehyde in the human esophageal tissue after ethanol drinking. Unexpectedly, intake of L-cysteine lozenges appears to contribute to detection of acetaldehyde in the esophageal tissue.
Effects of amino acids on acute alcohol intoxication in mice--concentrations of ethanol, acetaldehyde, acetate and acetone in blood and tissues.
Acetaldehyde levels in blood, liver and brain remained low by L-cysteine. Ethanol metabolites during alcohol oxidation by chemical reactabilities of L- and D-cysteine showed different distribution in the mice, respectively. In the mice received L-alanine, acetate and acetone levels in blood, liver and brain were distinctly reduced (p less than 0.01). L-Alanine is reported to supply an abundance of pyruvic acid that performs the NAD-generating system. NAD produced is introduced to alcohol metabolism and the TCA cycle. It was thus presumed that the L- or/and D-cysteine, and L-alanine was effective in acute alcohol intoxication by heavy drinking.
Natural Dietary Supplementation of Curcumin Protects Mice Brains against Ethanol-Induced Oxidative Stress-Mediated Neurodegeneration and Memory Impairment via Nrf2/TLR4/RAGE Signaling
According to our findings, ethanol triggered reactive oxygen species (ROS), apoptosis, neuroinflammation, and memory impairment, which were significantly inhibited with the administration of curcumin, as assessed by ROS, lipid peroxidation (LPO), and Nrf2/HO-1 (nuclear factor erythroid 2-related factor 2/Heme-oxygenase-1) expression in the experimental mice brains.
Low doses of curcumin protect alcohol-induced liver damage by modulation of the alcohol metabolic pathway, CYP2E1 and AMPK.
These findings indicate that low doses of curcumin may protect against liver damage caused by chronic alcohol intake and a high-fat diet partly by modulating the alcohol metabolic enzyme activity, the antioxidant activity and the lipid metabolism. Therefore, curcumin may provide a promising natural therapeutic strategy against liver disease.
Mechanisms of curcumin-induced gastroprotection against ethanol-induced gastric mucosal lesions
Curcumin, a pleiotropic substance used for centuries in traditional medicine, exhibits antioxidant, anti-inflammatory and antiproliferative efficacy against various tumours, but the role of curcumin in gastroprotection is little studied.
Curcumin confers neuroprotection against alcohol-induced hippocampal neurodegeneration via CREB-BDNF pathway in rats.
Alcohol abuse causes severe damage to the brain neurons. Studies have reported the neuroprotective effects of curcumin against alcohol-induced neurodegeneration.Curcumin can act as a neuroprotective agent against neurodegenerative effects of alcohol abuse, probably via activation of CREB-BDNF signaling pathway.