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What Are Sirtuins? Activators, Benefits and Food

Sirtuins are a family of 7 proteins which are key players in the role of regulating cellular homeostasis that helps keep the cell in balance.

Sirtuins help to regulate the systems in the body such as the brain, nerves, metabolism, heart, blood vessels and immune system.

3 out of the 7 proteins work in the mitochondria, 3 work in the nucleus and 1 works in the cytoplasm.

 

List of the 7 Sirtuins:

  • Sirt 1: human counterpart to Sir2 in yeast and is up-regulated when calorie restricted and shown to provide neurological support

  • Sirt 2: related to maintaining a healthy weight as obese people have decreased levels and increased levels in animals subject to calorie restriction

  • Sirt 3: potent antioxidant and low levels were shown to have high levels of oxidative damage from free radicals

  • Sirt 4: regulates insulin sensitivity and may help preserve telomere length

  • Sirt 5: appears to play a role in liver detoxification by regulating the step of coverting ammonia to urea for excretion
  • Sirt 6: suggested to be the most important sirtuin for longevity and has been shown in animals with low Sirt 6 levels to have dramatic aging in the first weeks of life, immune deficiency and bone degeneration
  • Sirt 7: shown in mice to correlate with premature aging

The main role of sirtuin is to remove the acetyl groups from other proteins which control specific reactions.

It removes acetyl groups from an amino acid called lysine found in proteins throughout the body.

Acetyl groups act as physical tags on proteins which other proteins recognise so that they react with them.

Sirtuins are modified by histone deacetylation and histones are the proteins which our DNA is wound.

When histones are deacetylated, it regulates gene expression – making sure genes are turned on and off at the right time.

Sirtuins are a type of protein which protect the cells in our bodies from dying or becoming inflamed through illness.

They also help regulate the metabolism, increase muscle and burn fat.

 

Types of Sirtuins

What Are Sirtfoods?

 

Sirtfoods are foods which may contribute to the upregulation of sirtuins and these are:

  • Kale

  • Onions

  • Parsley

  • Red Wine

  • Strawberries

  • Extra Virgin Olive Oil

  • Dark Chocolate (85% cocoa)

Benefits of Sirtuin Activators

 

  • Aging

  • Inflammation

  • Detoxification

  • Stress Resistance

  • Circadian Rhythms

  • Mitochondrial Biogenesis

  • Fat and Glucose Metabolism

Sirtuins and NAD+

 

The analogy between sirtuins and NAD+ can be compared to a driver in a car:

Sirtuins are the drivers of the vehicle (your body) and NAD+ is the gasoline that is required to drive the car and keep it moving.

Sirtuins are NAD-dependent and need NAD+ to function which is a coenzyme found in all living cells.

For sirtuins to carry out their job properly, they need NAD+.

As we age, our NAD+ levels are decreasing, and this leads to the sirtuins being limited in what they used to be able to do.

In your cells, sirtuins manage everything and acts as the boss at the cellular level.

 

How Can I Boost My Sirtuins?

 

Calorie restriction has been shown to slow the aging process and the reason why is that it stimulates sirtuin activity.

Research carried out in yeast found that:

  • Sir2 levels decreased with aging
  • Inhibiting Sir2 shortened lifespan
  • Increasing Sir 2 lengthened lifespan
  • Sir2 had a positive effect on telomere length

Our ancestors would have frequently fasted during food scarcity and could have altered our genome and it’s likely that the expression of sirtuins conferred survival benefits to our ancestors.

Sirt 1 and Sirt 3 are activated when fasting.

The most well-known natural substance to have a positive impact on sirtuins is Resveratrol.

Resveratrol is the compound in red wine which stimulates Sirt-1 expression and this may result in its antioxidant effects, improvements in insulin resistance and support for the nervous & muscular system.

It was also shown to increase Sirt-4 in a test tube and preserve telomeres.

Pterostilbene has been labelled as “Resveratrol’s cousin” and is found in blueberries in high amounts which has been shown to stimulate Sirt-1 activity.

Pterostilbene has also been shown to protect heart cells from oxygen deprivation by up-regulating Sirt-1.

Curcumin is a flavonoid from turmeric which has a myriad of positive benefits in supporting sirtuin expression.

Curcumin has been shown to protect nerve cells by up-regulating Sirt-1 and it has been shown to upregulate Sirt 1,3,5,6 and 7.

Melatonin – released just before sleep in the brain – has also been shown to protect the brain by up-regulating Sirt-1.

Quercetin is also a sirtuin activator and has demonstrated benefits for longevity, antioxidant and metabolic health-promoting effects.

It is a plant pigment found in fruits and vegetables such as onions and green tea.

 

Physical Exercise and Sirtuins

 

Physical exercise has been shown to have a positive effect on sirtuin levels and exercise was shown to inhibit muscle wasting, nerve degeneration and free radical damage.

As we age, research is indicating that the body doesn’t respond to exercise the same way it did when we were younger and this may be attributed to lower NAD+ levels and sirtuin activation.

Sufficient NAD+ levels in addition to sirtuin activation may help reactivate the response we had when we younger by enhancing the generation of mitochondria inside skeletal muscle cells.

 

Sources:

 

Rajman L, et al. Therapeutic potential of NAD-boosting molecules: the in vivo evidence. Cell Metab. 2018; 27(3): 529-547.

Imai SI and Guarente L. NAD+ and sirtuins in aging and disease. Trends Cell Biol. 2014; 24(8): 464-471.

Jesko H, et al. Sirtuins and their roles in brain aging and neurodegenerative disorders. Neurochem Res. 2017; 42(3): 876-890.

Houtkooper RH, et al. Sirtuins as regulators of metabolism and healthspan. Nat Rev Mol Cell Biol. 2012; 13(4): 225-238.

Radak Z, et al. The systemic role of SIRT1 in exercise mediated adaptation. Redox Biol. 2020; 35: 101467.

Mohar DS and Malik S. The sirtuin system: The holy grail of resveratrol? J Clin Exp Cardiolog. 2012; 3(11): 216.

Rahnasto-Rilla M, et al. Natural polyphenols as sirtuin 6 modulators. Sci Rep. 2018; 8: 4163.

Zhu Y, et al. Metabolic regulation of sirtuins upon fasting and the implication for cancer. Curr Opin Oncol. 2013; 25(6): 630-636.

Vargas-Ortiz K, et al. Exercise and sirtuins: A way to mitochondrial health in skeletal muscle. Int J Mol Sci. 2019; 20(11): 2717.

De Guia RM, et al. Aerobic and resistance exercise training reverses the age‐dependent decline in NAD+ salvage capacity in human skeletal muscle. Physiol Rep. 7(12): e14139.

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