Could Sirtuin 6 Activation Extend Lifespan in Humans?

by Nils Osmar – Updated March 20, 2022 – Medical Disclaimer

Sirtuins, or longevity genes, are highly evolutionarily conserved, meaning that they operate along pathways that have been integrated into life on Earth for literally billions of years, in both simple and complex organisms. Yeast, flies, fish, birds, and mammals all have sirtuins.

The activation of the sirtuins — particularly SIRT6 — is associated with an increase in both median and maximum lifespan in a number of life forms, and a similar increase in health span. But is there reason to believe it might have a similar effect in humans?

The truth is, we don’t know, and may not know for decades. It’s impossible (at this point) to prove that a given intervention increases the human lifespan, because it would take longer than a lifespan to prove it. Still, some people are focusing on switching on their sirtuins in the hopes that they may end up living longer and healthier lives as a result.

As with other compounds, we can draw some inferences from animal studies and population studies. There are of course limitations to both; people aren’t just big mice, and it can take time to tease out cause and effect. But there are some clues that products which activate the sirtuin 6 gene may turn out to be a key to living longer.

Ways of activating the SIRT6 gene include:

1. Eating foods or taking supplements containing fucoidan (derived from some types of seaweed and brown algae)
2. Eating dark purple berries (such as black elderberries) and taking berry extracts containing cyanidin
3. Prolonged water fasts (of 10 days or more)

Population studies

One product which some researchers believe may turn out to be effective at extending the human lifespan is fucoidan. A clue comes from population studies. There are communities in which people eat a lot of fucoidan-rich seaweed. Those who do have a tendency toward great longevity.

According to an article published in Life Extension Magazine:

Researchers believe fucoidans are partly responsible for the extraordinary longevity observed in Japanese populations, where organic, unpolluted seaweeds form a significant dietary component.

Fucoidans enhance immune function, combat infectious diseases, and support defense against cancer. Fucoidans also combat metabolic syndrome and cardiovascular disease by modulating glucose and insulin, disrupting formation of advanced glycation end products, and lowering triglyceride levels.

In human studies, fucoidans… demonstrate beneficial effects at doses of 75-300 mg daily.

Bioactive compounds

A study called “SIRT6 in Senescence and Aging-Related Cardiovascular Diseases” states that:

Brown seaweeds contain many bioactive compounds, including polyphenols, polysaccharides, fucosterol, and fucoxantin. These compounds have several biological activities, including anti-inflammatory, hepatoprotective, anti-tumor, anti-hypertensive, and anti-diabetic activity…

It has been demonstrated that increasing the sirtuin level through genetic manipulation extends the lifespan of yeast, nematodes and flies. Deficiency of SIRT6 induces chronic inflammation, autophagy disorder and telomere instability…

Animal studies

Animal studies aren’t perfect. But again, they can give us some reason for optimism. From a study called “Sirt6 regulates lifespan in Drosophila melanogaster“”

Sirt6 is well known for its role in regulating the aging process, particularly for its ability to extend lifespan in mice when overexpressed.

Here, we characterized dSirt6 in fruit flies (Drosophila melanogaster). We found that dSirt6 functions very similarly to mammalian Sirt6 at the molecular and biochemical levels.

Furthermore, overexpressing dSirt6 increased lifespan in flies. dSirt6 overexpression extends lifespan, in part, by opposing the activity of Myc, a master regulator of protein synthesis, which is associated with decreased protein synthesis.

These findings have relevance for the treatment of age-related disease by modulating Sirt6 activity…

Other studies

From a study called “Risks and benefits of consuming edible seaweeds“:

The recent surge of interest in seaweed is fueled by attention on the bioactive components of seaweed, which have potential applications in the lucrative functional food and nutraceutical industries, with impetus toward the alleviation of metabolic risk factors such as hyperglycemia, hypercholesterolemia, and hyperlipidemia

There is considerable evidence from animal studies to support a role for an effect of seaweed polyphenols on glucose and lipid digestion and metabolism, giving rise to suggestions that these polyphenols may have potential in preventing diabetes and obesity-associated complications. 

From a study called “Potential Anti-Aging Substances Derived from Seaweeds“:

The health benefits of seaweeds include, but are not limited to, antioxidant, anti-inflammatory, and anti-obese activities. Interestingly, a body of studies shows that some seaweed-derived extracts or isolated compounds, can modulate these aging-regulating pathways or even extend lifespans of various animal models. 

The sirtuin-NAD+ connection

According to a study called “Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators“, the sirtuin genes, including SIRT6, are NAD+-dependent.

Sirtuin 6 (SIRT6) is a nuclear NAD⁺–dependent deacetylase of histone H3 that regulates genome stability and gene expression.

This suggests that they would be most effective if NAD levels are high while taking them. (We can raise NAD by working out; by cold exposure; and by taking supplements such as NMN or NR, which are NAD+ precursors.)

Safety and side effects

• Before taking any supplement (or eating a food high in a nutrient), it makes sense to do a little research.
• Foods rich in cyanidin and fucoidan (which are the source of my supplements) have been consumed for centuries and appear to be safe. However, some types of berries (such as elderberries) containing cyanidin need to be cooked first to make them safe to consume. And people allergic to fish products may sometimes respond negatively to supplements derived from seaweed.
• One possible negative side effect of sirtuin 6 activation is that it may aggravate symptoms of Parkinsons. But it’s also associated with possible improvement in neurological functioning. And what’s true of animals isn’t always true in people. So as always, more studies are needed.

What I’m taking

• My strategy for activating the SIRT6 gene is to eat foods and/or take supplements high in both fucoidan and cyanidin, while trying to raise NAD levels around the same time.
• For cyanidin, I take Gaia Herbs Black Elderberry Extract
• For fucoidan, I take DoNotAge SIRT6 Activator
• I take both in the morning along with some NMN (a supplement which have been found to raise NAD levels).
• I also eat Wakame seaweed, though I’m still figuring out the best ways to include it in my meals.

What I’ve noticed:

I take a lot of supplements, so it’s hard sometimes to be sure which one is causing which reaction. But with SIRT6 activators I have noticed several effects:

• More energy
• More alertness
• My white chest hair and pale arm hair grew out and were replaced by lush, thick dark, somewhat curly hair (which I assume is from different genes being activated) (I’m not sure if this was because of adding SIRT 6 activators, or because I started taking AKG supplements around the same time.)
• Better results from my workout protocol (adding muscle faster)
• More sexual energy

What about you?

Are you focusing on activating SIRT6? If so, feel free to share your protocol and experiences (good or bad) in the comments section below.

References

• The Role of Mammalian Sirtuins in the Regulation of Metabolism, Aging, and Longevity
• The Identification of a SIRT6 Activator from Brown Algae Fucus distichus
• SIRT6 in Senescence and Aging-Related Cardiovascular Diseases
• Biological and catalytic functions of sirtuin 6 as targets for small-molecule modulators
• Sirt6 regulates lifespan in Drosophila melanogaster
• : “Risks and benefits of consuming edible seaweeds“

Image by Pete Linforth from Pixabay

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