Activation of the SIRT6 gene

Activation of the SIRT6 gene (sirtuin 6) is of great interest to science and medicine, as this gene plays a key role in regulating a variety of biological processes, including aging, metabolism, DNA repair, and inflammation. SIRT6 is a NAD+ – dependent deacetylase and mono-ADP-ribosyltransferase, and its activation can have a positive effect on health and life expectancy.

Main ways to activate the SIRT6 gene:

1. Pharmacological activation:

• SIRT6 Activators: There are small molecules that can directly activate SIRT6. For example:
  • MDL-800: A synthetic activator of SIRT6 that enhances its deacetylase activity and promotes improved metabolic health and DNA repair.
  • Cyanidin-3-Glucoside (C3G): A natural flavonoid that can activate SIRT6 and improve metabolic functions.
• NAD+ boosters: Since SIRT6 is a NAD+ – dependent enzymeEnzymes are proteins that accelerate chemical reactions in the body. They ensure the occurrence of metabolic processes such as food digestion, energy release, cell formation, and many others., increasing NAD+ levels in cells can increase its activity. Examples of NAD+ boosters:
  • Nicotinamide riboside (NR),
  • Nicotinamide mononucleotide (NMN).

2. Dietary and natural compounds:

• Resveratrol: A polyphenol found in red grapes and berries that can indirectly activate SIRT6 by increasing NAD+levels.
• Quercetin: A flavonoid with antioxidant properties that can stimulate the activity of sirtuins, including SIRT6.
• Curcumin: An active component of turmeric that can modulate SIRT6 activity and have an anti-inflammatory effect.

3. Genetic approaches:

• Gene therapy: The introduction of additional copies of the SIRT6 gene using viral vectors (for example, adenoviruses or lentiviruses) to increase its expression.
• CRISPR activation: Using the CRISPR / Cas9 system for targeted activation of the SIRT6 gene. For example, the use of dCas9 (deactivated Cas9) in combination with activator domains (for example, VP64) to enhance SIRT6 transcription.

4. Epigenetic regulation:

• Histone Deacetylase inhibitors (HDACs): Some HDAC inhibitors may indirectly affect SIRT6 expression by altering the epigenetic landscape.
• Histone modification: Acetylation or methylation of histones in the promoter region of the SIRT6 gene can regulate its expression.

5. Physiological and metabolic stimuli:

• Caloric restriction: Reducing caloric intake is one of the most effective ways to activate sirtuins, including SIRT6. This is due to an increase in NAD+ levels and activation of AMPK (AMP-activated protein kinase).
• Physical Activity: Regular exercise can increase NAD+ levels and activate SIRT6, improving metabolic health and DNA repair.

6. miRNAs:

• Some miRNAs may regulate SIRT6 expression. For example, suppressing miRNAs that inhibit SIRT6 may increase its activity.

Possible effects of SIRT6 activation:

• Increased life expectancy: SIRT6 plays an important role in protecting against age-related diseases.
• Improved Metabolism: Activating SIRT6 can improve insulin sensitivity and reduce the risk of diabetes.
• Cancer protection: SIRT6 is involved in the suppression of tumor growth through the regulation of DNA repair and cancer cell metabolism.
• Reduced inflammation: SIRT6 modulates inflammatory processes, which may be useful in chronic diseases.

Current research:

SIRT6 activation is actively studied in preclinical and clinical studies. For example:

• Studies in mice have shown that activating SIRT6 can improve metabolic health and increase life expectancy.
• NAD+ boosters (such as NMN and NR) are being studied in clinical trials to activate sirtuins, including SIRT6.