Nutraceutical activation of Sirt1: a review

Abstract

The deacetylase sirtuin 1 (Sirt1), activated by calorie restriction and fasting, exerts several complementary effects on cellular function that are favourable to healthspan; it is often thought of as an ‘anti-aging’ enzyme. Practical measures which might boost Sirt1 activity are therefore of considerable interest. A number of nutraceuticals have potential in this regard. Nutraceuticals reported to enhance Sirt1 synthesis or protein expression include ferulic acid, tetrahydrocurcumin, urolithin A, melatonin, astaxanthin, carnosic acid and neochlorogenic acid. The half-life of Sirt1 protein can be enhanced with the natural nicotinamide catabolite N1-methylnicotinamide. The availability of Sirt1’s obligate substrate NAD+ can be increased in several ways: nicotinamide riboside and nicotinamide mononucleotide can function as substrates for NAD+ synthesis; activators of AMP-activated kinase—such as berberine—can increase expression of nicotinamide phosphoribosyltransferase, which is rate limiting for NAD+ synthesis; and nutraceutical quinones such as thymoquinone and pyrroloquinoline quinone can boost NAD+ by promoting oxidation of NADH. Induced ketosis—as via ingestion of medium-chain triglycerides—can increase NAD+ in the brain by lessening the reduction of NAD+ mediated by glycolysis. Post-translational modifications of Sirt1 by O-GlcNAcylation or sulfonation can increase its activity, suggesting that administration of glucosamine or of agents promoting hydrogen sulfide synthesis may aid Sirt1 activity. Although resveratrol has poor pharmacokinetics, it can bind to Sirt1 and activate it allosterically—as can so-called sirtuin-activating compound drugs. Since oxidative stress can reduce Sirt1 activity in multiple ways, effective antioxidant supplementation that blunts such stress may also help preserve Sirt1 activity in some circumstances. Combination nutraceutical regimens providing physiologically meaningful doses of several of these agents, capable of activating Sirt1 in complementary ways, may have considerable potential for health promotion. Such measures may also amplify the benefits of sodium-glucose cotransporter-2 (SGLT2) inhibitors in non-diabetic disorders, as these benefits appear to reflect upregulation of Sirt1 and AMP-activated protein kinase activities.

Effect of Resveratrol on Markers of Oxidative Stress and Sirtuin 1 in Elderly Adults with Type 2 Diabetes

“…We also observed a statistically significant increase in SIRT1 concentrations in the EG1000, which is consistent with the proposed mechanism of RV [ 63 , 64 ]. In this sense, SIRT1 has an effect on the regulation of autophagy, mitophagy, mitochondrial biogenesis, the expression of antioxidant enzymes and the suppression of NFκB, among others [ 63 ].…”

“…We also observed a statistically significant increase in SIRT1 concentrations in the EG1000, which is consistent with the proposed mechanism of RV [ 63 , 64 ]. In this sense, SIRT1 has an effect on the regulation of autophagy, mitophagy, mitochondrial biogenesis, the expression of antioxidant enzymes and the suppression of NFκB, among others [ 63 ]. Likewise, the production, expression and activity of SIRT1 can be modified by RV in an allosteric way [ 64 ] so that an increase in SIRT1 levels provides indirect information on the effects of RV [ 63 ].…”

“…In this sense, SIRT1 has an effect on the regulation of autophagy, mitophagy, mitochondrial biogenesis, the expression of antioxidant enzymes and the suppression of NFκB, among others [ 63 ]. Likewise, the production, expression and activity of SIRT1 can be modified by RV in an allosteric way [ 64 ] so that an increase in SIRT1 levels provides indirect information on the effects of RV [ 63 ]. On the other hand, when SIRT1 is stimulated, it deacetylates and activates the LKB1 protein kinase, which phosphorylates and activates AMPK, thereby attenuating oxidative damage, improving insulin resistance and restoring energy homeostasis [ 64 ].…”

Antioxidant and Antidiabetic Potential of Ormocarpum cochinchinense (Lour.) Merr. Leaf: An Integrated In vitro and In silico Approach

“…Myo‐inositol supplementation has been found to reduce obesity, increase the sensitivity of insulin, and lower fasting and postprandial blood glucose levels in people with type 2 diabetes [37] . In addition, myo‐inositol has demonstrated advantages in illnesses like gestational diabetes, PCOS, and metabolic disorders [38,39] …”

Positive Tetrahydrocurcumin-Associated Brain-Related Metabolomic Implications

“…Ma et al [10], investigating the relationship between the antioxidative brain potential of brain tissue and cognitive impairment in a C57BL/6 mouse model induced by acute hypobaric hypoxia, discovered that THC improved cognitive impairment, accompanied by reduced oxidative stress and increased glucose transporter 1 (GLUT1) protein levels. In addition, one crucial brain-related THC-affected mechanism is the synthesis of the deacetylase, sirtuin 1 (Sirt1) [11]. Sirt1's activity is associated with improved cellular physiological function and is considered to have an anti-aging effect.…”